ORCID Profile
0000-0002-6943-6908
Current Organisation
Western Sydney University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Bioinorganic Chemistry | Chemical Spectroscopy | Inorganic Chemistry | Physical Chemistry (Incl. Structural) | Other Physical Sciences | Nanotechnology | Biochemistry and Cell Biology | Biological And Medical Chemistry | Transition Metal Chemistry | Electrochemistry | Characterisation Of Macromolecules | Synchrotrons; Accelerators; Instruments and Techniques | Medical Physics | Transport Properties and Non-Equilibrium Processes | Biophysics | Toxicology (Incl. Clinical Toxicology) | Cell Metabolism | Gene Expression | Nanotechnology | Clinical Chemistry | Microbial Genetics | Materials Engineering Not Elsewhere Classified | Condensed Matter Imaging
ANZSRC Socio-Economic Objective (SEO)
Chemical sciences | Treatments (e.g. chemicals, antibiotics) | Biological sciences | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Physical Sciences | Beverages (e.g. alcohol, wines, soft drinks, excl. fruit juices) | Diagnostic methods | Physical sciences | Expanding Knowledge in the Earth Sciences | Cancer and Related Disorders | Diagnostics |
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Publications
The binding of [(en)Pt(μ-dpzm)2 Pt(en)]4+ to G/C-rich regions of DNA
Publisher: Elsevier BV
Date: 03-2001
DOI: 10.1016/S0162-0134(00)00206-3
Abstract: The non-covalent binding of [(en)Pt(mu-dpzm)2Pt(en)]4+ to segments of DNA containing only G and C bases has been studied to gain an understanding of the pre-covalent binding association of cationic polynuclear platinum(II) anti-cancer drugs at G/C sites. 1H-NMR and CD spectroscopy were used to study the binding of the metal complex to the oligonucleotide d(GC)5 and the polynucleotide poly(dG-dC).poly(dG-dC), respectively. NOE contacts between the metal complex protons and the oligonucleotide sugar H1' protons observed in NOESY spectra indicated that the metal complex bound in the minor groove at the central C4 to G7 region of the oligonucleotide. This result indicates that even though cationic polynuclear platinum(II) complexes bind covalently in the major groove at G/C sites, the pre-covalent binding association is favoured in the minor groove. CD spectra indicated that the addition of the metal complex to poly(dG-dC)-poly(dG-dC) induced some conformational changes, but it was not possible to conclude that [(en)Pt(mu-dpzm)2Pt(en)]4+ induced a B- to Z-type DNA transition. In addition, in vitro transcription assays using the lac UV5 promoter showed that the non-covalent binding of [(en)Pt(mu-dpzm)2Pt(en)]4+ was sufficiently stable to inhibit transcription, and at particular sites.
Probing DNA selectivity of ruthenium metallointercalators using ESI mass spectrometry
Publisher: Royal Society of Chemistry (RSC)
Date: 10-02-2003
DOI: 10.1039/B212132H
Abstract: ESI mass spectra show that up to five ruthenium molecules can bind non-covalently to double stranded 16mer DNA, and provide information on the relative affinity and DNA sequence selectivity of different ruthenium complexes.
An optimised approach for continuous-flow solid-phase peptide synthesis utilising a rudimentary flow reactor
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8RE00190A
Abstract: From the repurposing of used HPLC components, a chromatography column, a Rheodyne,® and a heater stirrer, a simple, cost-effective system to conveniently conduct continuous flow solid-phase peptide construction was assembled.
Comparison of mass spectrometry and other techniques for probing interactions between metal complexes and DNA
Publisher: American Chemical Society (ACS)
Date: 09-07-2008
DOI: 10.1021/IC702179A
Abstract: Electrospray ionization mass spectrometry (ESI-MS) was used to study the binding interactions of two series of ruthenium complexes, [Ru(phen) 2L] (2+) and [RuL' 2(dpqC)] (2+), to a double stranded DNA hexadecamer, and derive orders of relative binding affinity. These were shown to be in good agreement with orders of relative binding affinity derived from absorption and circular dichroism (CD) spectroscopic examination of the same systems and from DNA melting curves. However, the extent of luminescence enhancement caused by the addition of DNA to solutions of the ruthenium complexes showed little correlation with orders of binding affinity derived from ESI-MS or any of the other techniques. Overall the results provide support for the validity of using ESI-MS to investigate non-covalent interactions between metal complexes and DNA.
Does the metal influence non-covalent binding of complexes to DNA?
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B814156H
Abstract: Electrospray ionisation mass spectrometry, absorption spectrophotometry and circular dichroism spectroscopy were used to investigate the binding of a series of nickel complexes with the general formula [Ni(phen)2L]2+ (L = phen, dpq, dpqC and dppz) to a double stranded DNA hexadecamer. In addition, the binding of the complexes to pUC9 negatively supercoiled plasmid DNA was examined using gel electrophoresis, and their ability to inhibit DNA transcription was measured. Each of the above techniques showed that DNA binding strengthened as the size of the unique ligand L was increased. Comparison of the above results with those obtained previously, and presented here for the first time for the analogous series of ruthenium complexes [Ru(phen)2L]2+, showed that changing the metal ion from nickel to ruthenium consistently resulted in significant increases in DNA binding affinity.
Does cytotoxicity of metallointercalators correlate with cellular uptake or DNA affinity?
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2DT30217A
Abstract: The cytotoxicity of the metallointercalators, [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1R,2R-diaminocyclohexane)](2+) ([56MERR]) and [Pt(5,6-dimethyl-1,10-phenanthroline)(trans-1S,2S-diaminocyclohexane)](2+) ([56MESS]), towards A549 human lung cancer cells was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) value obtained following exposure of A549 cells to [56MESS] for 4 h was approximately three times smaller than that obtained when [56MERR] was administered under the same conditions, indicating that the former complex displayed greater cytotoxicity. Both IC(50) values were greater than that obtained after exposure of A549 cells to cisplatin, demonstrating that the latter compound was the most cytotoxic of the three examined. Microprobe synchrotron radiation X-ray fluorescence (SR-XRF) analyses of metallointercalator-treated A549 cells showed that platinum became localised in DNA-rich regions of the nucleus. In contrast, when the same cells were treated with cisplatin the metal became distributed throughout the cell. Determination of the maximum concentration of platinum present inside the cells using graphite furnace atomic absorption spectrophotometry (GFAAS) of platinum-treated cells suggested that there was greater uptake of [56MERR] compared to [56MESS] by the A549 cells, and that platinum uptake did not account for the greater toxicity of [56MESS], as assessed by the MTT assay. Electrospray ionization mass spectrometric (ESI-MS) and circular dichroism (CD) spectroscopic studies of solutions containing either [56MERR] or [56MESS], and a duplex hexadecamer molecule, showed the two metallointercalators displayed very similar affinity towards the nucleic acid. Overall these results indicate that the difference in cytotoxicity of the two platinum metallointercalators is probably the result of variations in their interactions with other cellular components.
Immobilized Carbodiimide Assisted Flow Combinatorial Protocol to Facilitate Amide Coupling and Lactamization
Publisher: American Chemical Society (ACS)
Date: 13-04-2020
Cyclooxygenase-Inhibiting Platinum(IV) Prodrugs with Potent Anticancer Activity
Publisher: MDPI AG
Date: 03-04-2022
DOI: 10.3390/PHARMACEUTICS14040787
Abstract: Platinum(IV) prodrugs of the [Pt(PL)(AL)(COXi)(OH)]2+ type scaffold (where PL is 1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, AL is 1S,2S-diaminocyclohexane, and COXi is a COX inhibitor, either indomethacin or aspirin) were synthesised and characterised, and their biological activity was explored. MTT assays showed that these complexes exhibit outstanding activity against a range of cancer cell lines, and nanomolar activities were observed. The most potent complex, 4, exhibited a GI50 of 3 nM in the Du145 prostate cancer cell line and was observed to display a 1614-fold increased activity against the HT29 colon cancer cell line relative to cisplatin. ICP-MS studies showed a linear correlation between increased cellular accumulation of the complexes and increased cytotoxicity, while an enzyme immunoassay showed that 1 and 2 inhibited COX-2 at 14 and 1.4 µM, respectively, which is comparable to the inhibition exhibited by indomethacin. These results suggest that while the cytotoxicity of prodrugs 1–4 was influenced by cellular uptake, it was not entirely dependent on either COX inhibition or lipophilicity.
Discrepancy between in vitro and in vivo antitumor effect of a new platinum(II) metallointercalator
Publisher: Springer Science and Business Media LLC
Date: 10-06-2010
DOI: 10.1007/S10637-010-9461-Z
Abstract: Platinum(II) metallointercalators represent a new class of DNA-damaging antitumor complexes active in cisplatin- and oxaliplatin-resistant cell lines. In the first part of our work, we have screened in vitro a serie of 18 metallointercalators with the structure [Pt(A(L))(I(L))](2+) where A(L) = ethylenediamine (EN) or diaminocyclohexane in R,R- (RR) or S,S- (SS) configuration and I(L) = 1,10-phenanthroline with different degree of methylation : no methylation (PHEN), mono-methylated in position 4 (4ME) or 5 (5ME), or di-methylated in positions 4 and 7 (47ME) or in positions 5 and 6 (56ME) or tetramethylated in positions 3,4,7 and 8 (3478ME). Eight compounds: PHENEN, 56MEEN, 47MERR, 56MERR, 4MESS, 5MESS, 47MESS and 56MESS exhibited significant cytotoxic effect, equivalent or higher than cisplatin, oxaliplatin or carboplatin in the human HCT8 colon and IGROV1 ovarian cancer cell lines for both 1 and 24 h incubation time. The high cytotoxicity of the most active compound, the 56MESS, could be related to the hydrophobicity of the phenanthroline ligand that increases cellular uptake in human HCT8, HT29 (colon) and IGROV1 (ovarian) as well as in rat PROb colon cell lines. Unfortunately, intravenous or intraperitoneal administration of 56MESS had no antitumoral activity in BD-IX rats with peritoneal carcinomatosis induced by an intraperitoneal PROb cells inoculation. Moreover, 56MESS displayed nephrotoxicity at pharmacological dose. Thus, these data query the in vivo/in vitro correlation and reconsider the place of the in vivo screening to select adequate candidate drug for further preclinical and clinical developments.
Separation of poly(acrylic acid) salts according to topology using capillary electrophoresis in the critical conditions
Publisher: Springer Science and Business Media LLC
Date: 04-06-2013
DOI: 10.1007/S00216-013-7059-Y
Abstract: Branching was detected in polyacrylates synthesised through radical polymerization via solution-state NMR, while inconsistencies have been reported for the determination of the molar mass of hydrophilic polyacrylates using aqueous-phase and organic-phase size-exclusion chromatography. In this work, poly(sodium acrylate)s, PNaAs, of various topologies were separated for the first time using free-solution capillary electrophoresis (CE). Free-solution CE does not separate the PNaAs by their molar mass, similarly to separations by liquid chromatography in the critical conditions, rather by different topologies (linear, star branched, and hyperbranched). The electrophoretic mobility of PNaAs increases as the degree of branching decreases. Separation is shown to be not only by the topology but also by the end groups as expected for a separation in the critical conditions: replacing a relatively bulky nitroxide end group with hydrogen atom yielded a higher electrophoretic mobility. This novel method, capillary electrophoresis in the critical conditions enabled, for the first time, the separation of hydrophilic polyacrylates according to their topology (branching) and their chain ends. This will allow meaningful and accurate characterization of their branched topologies as well as molar masses and progress in for advanced applications such as drug delivery or flocculation.
The host-guest chemistry of proflavine with cucurbit[6,7,8]urils
Publisher: Informa UK Limited
Date: 10-2007
Versatile Platinum(IV) Prodrugs of Naproxen and Acemetacin as Chemo-Anti-Inflammatory Agents
Publisher: MDPI AG
Date: 26-04-2023
Abstract: Developing new and versatile platinum(IV) complexes that incorporate bioactive moieties is a rapidly evolving research strategy for cancer drug discovery. In this study, six platinum(IV) complexes (1–6) that are mono-substituted in the axial position with a non-steroidal anti-inflammatory molecule, naproxen or acemetacin, were synthesised. A combination of spectroscopic and spectrometric techniques confirmed the composition and homogeneity of 1–6. The antitumour potential of the resultant complexes was assessed on multiple cell lines and proved to be significantly improved compared with cisplatin, oxaliplatin and carboplatin. The platinum(IV) derivatives conjugated with acemetacin (5 and 6) were determined to be the most biologically potent, demonstrating GI50 values ranging between 0.22 and 250 nM. Remarkably, in the Du145 prostate cell line, 6 elicited a GI50 value of 0.22 nM, which is 5450-fold more potent than cisplatin. A progressive decrease in reactive oxygen species and mitochondrial activity was observed for 1–6 in the HT29 colon cell line, up to 72 h. The inhibition of the cyclooxygenase-2 enzyme was also demonstrated by the complexes, confirming that these platinum(IV) complexes may reduce COX-2-dependent inflammation and cancer cell resistance to chemotherapy.
Synthesis, characterisation and anti bacterial testing of bismuth maltol
Publisher: Elsevier BV
Date: 07-2003
CHAPTER 9 Biomolecular Interactions of Platinum Complexes
Publisher: The Royal Society of Chemistry
Date: 04-09-2013
DOI: 10.1039/9781849737821-00260
Abstract: Deoxyribonucleic acid is generally accepted as the primary biomolecular target of the first platinum-based chemotherapeutic agent, cisplatin, which was documented in 1845, characterised in 1893 and its potential discovered in 1965. Initial attempts to understand the structural significance of the compound by combinatorial means saw early conceptions of structure–activity relationships that were soon challenged. Almost 50 years and thousands of complexes later, DNA still remains the primary target in a variety of interactions ranging from differences in base-pair preference, irreversible covalent binding, and reversible minor/major groove binding and intercalation. Developmental efforts have seen active cytotoxic platinum complexes with structures derived beyond initial assumptions through a ersity of ligand substitution and multinuclear linkages. Nonetheless nephrotoxicity and neurotoxicity pose as dire inherent side-effects in clinical trials and application of platinum therapeutics. Subsequent development has called for means to avoid diminished efficacy due to inactivation by endogenous glutathione and other complex-binding or chelating proteins. Platinum(IV) derivatives may solve issues of unintended toxicity by means of intrinsic extracellular stability, degrading to their active platinum(II) forms once internalised within a cytosol and in acidic tumour environments. Selectivity may also be gained by the axial/apical coordination of ligands that typically bind to receptors that are overexpressed in certain tumours, such as modified-estrogen ligands. The development of platinum complexes has required an in-depth understanding of their DNA-binding interactions in order to facilitate further structural modification without loss of effective function for their eventual application as chemotherapeutics. Although platinum complexes are the focus of this chapter, some other metal complexes that interact with nucleic acids, such as ruthenium, iridium, osmium, iron, copper, titanium, vanadium gold and silver, are discussed.
Studies of the Mechanism of Action of Platinum(II) Complexes with Potent Cytotoxicity in Human Cancer Cells
Publisher: American Chemical Society (ACS)
Date: 06-08-2009
DOI: 10.1021/JM9007104
Abstract: We have examined the biological activity of 12 platinum(II)-based DNA intercalators of the type [Pt(I(L))(A(L))](2+), where I(L) is an intercalating ligand (1,10-phenanthroline or a methylated derivative) and A(L) is an ancillary ligand (diaminocyclohexane, diphenylethylenediamine or 1,2-bis(4-fluorophenyl)-1,2-ethylenediamine). The chiral compounds (1-9) and the racemic compounds (10-12) were tested against a panel of human cancer cell lines, with a number of complexes displaying activity significantly greater than that of cisplatin (up to 100-fold increase in activity in the A-427 cell line). The activity of the complexes containing diphenylethylenediamine (8 and 9) and 1,2-bis(4-fluorophenyl)-1,2-ethylenediamine (10-12) was significantly lower compared to the complexes containing diaminocyclohexane (1-7). Further in vitro testing, such as DNA unwinding, competition assays, and DNase 1 footprinting, was conducted on the most active compound (5) and its enantiomer (6) to provide information about the mechanism of action. These complexes display activity in cisplatin resistant cell lines, have higher cellular uptake than cisplatin, and do not activate caspase-3 as cisplatin does, indicating that these complexes exhibit a different mechanism of action.
Terpyridineplatinum(II) Incorporation in N‐Methylpyrrole‐Based Polyamides by Solid Phase Techniques
Publisher: Wiley
Date: 10-2008
Synthesis and characterisation of platinum(IV) polypyridyl complexes with halide axial ligands
Publisher: Elsevier BV
Date: 09-2019
Transition Metal Based Anticancer Drugs
Publisher: Bentham Science Publishers Ltd.
Date: 03-2011
DOI: 10.2174/156802611794785226
Abstract: With an ageing baby-boomer population in the Western World, cancer is becoming a significant cause of death. The prevalence of cancer and all associated costs, both in human and financial terms, drives the search for new therapeutic drugs and treatments. Platinum anticancer agents, such as cisplatin have been highly successful but there are several disadvantages associated with their use. What is need are new compounds with different mechanisms of action and resistance profiles. What needs to be recognised is that there are many other metal in the periodic table with therapeutic potential. Here we have highlighted metal complexes with activity and have illustrate the different approaches to the design of anticancer complexes.
Novel platinum(ii)-based anticancer complexes and molecular hosts as their drug delivery vehicles
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B704973K
Abstract: Platinum(II)-based DNA intercalators where the intercalating ligand is 1,10-phenanthroline or a phenanthroline derivative and where the ancillary ligand is either achiral (e.g. ethylenediamine) or chiral (e.g. diaminocyclohexane) show a range of cytotoxicities with a defined structure-activity relationship. The most cytotoxic are those that contain methylated-phenanthroline ligands and 1S,2S-diaminocyclohexane (S,S-dach) as the ancillary ligand. We have developed a new purification method using Sep-Pak C-18 reverse phase columns, which means these metal complexes can be made faster and cheaper compared to published methods. Platinum(II)-based complexes containing imidazole, pyrrole and beta-alanine subunits, that are capable of recognising specific DNA base-pair sequences have also been synthesised. These include linear or hairpin polyamide ligands that can recognise DNA sequences up to seven base-pairs in length and contain single platinum centres capable of forming monofunctional adducts with DNA. We have now synthesised and characterised, by (1)H and (195)Pt NMR, ESI-MS and elemental analysis, the first dinuclear platinum(II) DNA sequence selective agent. Finally, using (1)H NMR we have examined the encapsulation of our platinum(II)-based DNA intercalators by cucurbit[6]uril (CB[6]). Encapsulation by CB[6] was found to not significantly change the cytotoxicity of five platinum(II)-based DNA intercalators, indicating it may have utility as a molecular carrier for improved drug delivery.
Metal complex interactions with DNA
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4DT02700K
Abstract: Increasing numbers of DNA structures are being revealed using a erse range of transition metal complexes and biophysical spectroscopic techniques. Here we present a review of metal complex-DNA interactions in which several binding modes and DNA structural forms are explored.
Synthesis and characterisation of two Cu(I) metalloligands based on tetradentate tripodal ligands
Publisher: Elsevier BV
Date: 03-2017
Drug induced self-assembly of triblock copolymers into polymersomes for the synergistic dual-drug delivery of platinum drugs and paclitaxel
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7PY01162H
Abstract: Co-delivery of two drugs in one nanoparticle is increasingly used to overcome, for ex le, multi-drug resistance in cancer therapy and therefore suitable drug carriers need to be developed.
Chronic neuroinflammation in Alzheimer's disease: new perspectives on animal models and promising candidate drugs.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/309129
Abstract: Chronic neuroinflammation is now considered one of the major factors in the pathogenesis of Alzheimer’s disease (AD). However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau) do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system), and cognitive decline that is comparable with the human disease. Hence a more suitable animal model is needed to more closely mimic the resulting cognitive decline and memory loss in humans in order to investigate the effects of neuroinflammation on neurodegeneration. One of these models is the glial fibrillary acidic protein-interleukin 6 (GFAP-IL6) mouse, in which chronic neuroinflammation triggered constitutive expression of the cytokine interleukin-6 (IL-6) in astrocytes. These transgenic mice show substantial and progressive neurodegeneration as well as a decline in motor skills and cognitive function, starting from 6 months of age. This animal model could serve as an excellent tool for drug discovery and validation in vivo . In this review, we have also selected three potential anti-inflammatory drugs, curcumin, apigenin, and tenilsetam, as candidate drugs, which could be tested in this model.
Chiral Platinum(II) Metallointercalators with Potent in vitro Cytotoxic Activity
Publisher: Wiley
Date: 04-04-2007
Abstract: Four platinum(II) metallointercalating complexes of 1,10-phenanthroline (phen) with the chiral ancillary ligands trans-R,R- and trans-S,S-1,2-diaminocyclohexane (R,R- and S,S-dach, respectively), and N,N'-dimethyl-R,R- and N,N'-dimethyl-S,S-1,2-diaminocyclohexane (Me(2)-R,R-dach and Me(2)-S,S-dach, respectively) have been synthesised and characterised. The crystal structure of [Pt(Me(2)-S,S-dach)(phen)](ClO(4))(2)1.5 H(2)O (C(20)H(26)Cl(2)N(4)O(9.5)Pt) has been determined orthorhombic, space group P2(1)2(1)2(1)(No. 19), a=23.194(8), b=25.131(9), c=8.522(3) A. In vitro cytotoxic assays (IC(50)) in the human bladder cancer cell line 5637 and in the murine leukemia L1210 cell line revealed that [Pt(S,S-dach)(phen)](ClO(4))(2) (0.091 and 0.13 microM, respectively) and [Pt(R,R-dach)(phen)](ClO(4))(2) (0.54 and 1.50 microM, respectively) were more cytotoxic than cisplatin (0.31 and 0.50 microM, respectively) and considerably more cytotoxic than their methylated counterparts, [Pt(Me(2)-R,R-dach)(phen)](ClO(4))(2) and [Pt(Me(2)-S,S-dach)(phen)](ClO(4))(2) (both>23 microM). Chiral discrimination for [Pt(S,S-dach)(phen)](ClO(4))(2) over its R,R-enantiomer was observed in all 13 cancer cell lines investigated. Moreover, [Pt(S,S-dach)(phen)](ClO(4))(2) was more active than cisplatin in all cell lines tested and shows only partial cross-resistance to cisplatin in two cisplatin resistant cell lines.
Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties
Publisher: MDPI AG
Date: 09-09-2022
Abstract: Herein is described the development of a series of novel quadruplex DNA (QDNA)-stabilising cyclometallated square–planar metal complexes (CMCs). Melting experiments using quadruplex DNA (QDNA) demonstrated that interactions with the complexes increased the melting temperature by up to 19 °C. This QDNA stabilisation was determined in two of the major G-quadruplex structures formed in the human c-MYC promoter gene (c-MYC) and a human telomeric repeat sequence (H-Telo). The CMCs were found to stabilise H-telo more strongly than c-MYC, and the CMCs with the highest cytotoxic effect had a low–moderate correlation between H-telo binding capacity and cytotoxicity (R2 values up to 10 times those of c-MYC). The melting experiments further revealed that the stabilisation effect was altered depending on whether the CMC was introduced before or after the formation of QDNA. All CMCs’ GI50 values were comparable or better than cisplatin in human cancer cell lines HT29, U87, MCF-7, H460, A431, Du145, BE2-C, SJ-G2, MIA, and ADDP. Complexes 6, 7, and 9 were significantly more cytotoxic than cisplatin in all cell lines tested and had good to moderate selectivity indices, 1.7–4.5 in MCF10A/MCF-7. The emission quantum yields were determined to be relatively high (up to 0.064), and emission occurred outside cellular autofluorescence, meaning CMC fluorescence is ideal for in vitro analyses.
Combination studies of platinum(ii )-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin
Publisher: Oxford University Press (OUP)
Date: 2014
DOI: 10.1039/C3MT00191A
Abstract: With current chemotherapeutic treatment regimes often limited by adverse side effects, the synergistic combination of complexes with anticancer activity appears to offer a promising strategy for effective cancer treatment. This work investigates the anti-proliferative activity using a combination therapy approach where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the intercalating ligand and AL is the ancillary ligand) are used in combination with currently approved anticancer drugs cisplatin and carboplatin and organic molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic relationships were observed, indicating a potential to decrease dose-dependent toxicity and improve therapeutic efficacy.
Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry
Publisher: American Chemical Society (ACS)
Date: 10-2004
DOI: 10.1016/J.JASMS.2004.07.005
Abstract: Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from free DNA were present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase.
Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils
Publisher: Springer Science and Business Media LLC
Date: 25-07-2007
DOI: 10.1007/S00775-007-0269-Z
Abstract: The partial encapsulation of platinum(II)-based DNA intercalators of the type [Pt(5-Cl-phen)(ancillary ligand)](2+), where 5-Cl-phen is 5-chloro-1,10-phenanthroline and the ancillary ligand is ethylenediamine, (1S,2S)-diaminocyclohexane (S,S-dach) or (1R,2R)-diaminocyclohexane, within cucurbit[n]uril (CB[n], where n is 6, 7 or 8) has been examined by (1)H and (195)Pt NMR and mass spectrometry. For CB[7], the molecule encapsulates over the ancillary ligand of all metal complexes, whether this is ethylenediamine or diaminocyclohexane. For CB[8], encapsulation occurs over the sides of the 5-Cl-phen ligand at low [Pt(5-Cl-phen)(S,S-dach)](2+) (5CLSS) to CB[8] ratios (i.e. 0.25:1) but over the ancillary ligand at higher ratios (i.e. 2:1). For CB[6] binding, 5CLSS exhibits both portal and cavity binding, with the ancillary ligand displaying chemical shifts consistent with fast exchange kinetics on the NMR timescale for portal binding and slow exchange kinetics for cavity binding. Binding constants could not be determined using UV-vis, circular dichroism or fluorescence spectrophotometry, but a binding constant for binding of 5CLSS to CB[6] of approximately 10(5) M(-1) was determined using (1)H NMR. Finally, the effect of CB[n] encapsulation on the cytotoxicity of the metal complexes was examined using L1210 murine leukaemia cells in vitro growth inhibition assays. The cytotoxicity is highly dependent on both the metal complex and the CB[n] size, and whilst CB[7] and CB[8] generally decreased cytotoxicity, it was found that CB[6] increased the cyotoxicity of 5CLSS up to 2.5-fold.
Potent Chlorambucil-Platinum(IV) Prodrugs
Publisher: MDPI AG
Date: 09-09-2022
Abstract: The DNA-alkylating derivative chlorambucil was coordinated in the axial position to atypical cytotoxic, heterocyclic, and non-DNA coordinating platinum(IV) complexes of type, [PtIV(HL)(AL)(OH)2](NO3)2 (where HL is 1,10-phenanthroline, 5-methyl-1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, AL is 1S,2S-diaminocyclohexane). The resultant platinum(IV)-chlorambucil prodrugs, PCLB, 5CLB, and 56CLB, were characterized using high-performance liquid chromatography, nuclear magnetic resonance, ultraviolet-visible, circular dichroism spectroscopy, and electrospray ionization mass spectrometry. The prodrugs displayed remarkable antitumor potential across multiple human cancer cell lines compared to chlorambucil, cisplatin, oxaliplatin, and carboplatin, as well as their platinum(II) precursors, PHENSS, 5MESS, and 56MESS. Notably, 56CLB was exceptionally potent in HT29 colon, Du145 prostate, MCF10A breast, MIA pancreas, H460 lung, A2780, and ADDP ovarian cell lines, with GI50 values ranging between 2.7 and 21 nM. Moreover, significant production of reactive oxygen species was detected in HT29 cells after treatment with PCLB, 5CLB, and 56CLB up to 72 h compared to chlorambucil and the platinum(II) and (IV) precursors.
Synthesis, characterisation and influence of lipophilicity on cellular accumulation and cytotoxicity of unconventional platinum(iv ) prodrugs as potent anticancer agents
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9DT04049H
Abstract: Unconventional lipophilic Pt( iv ) complexes exhibited enhanced cellular accumulation compared to their hydrophilic Pt( iv ) precursors, however no clear correlation was observed between increasing lipophilicity, cellular accumulation and cytotoxicity.
Paper: A cheap yet effective chiral stationary phase for chromatographic resolution of metallo-supramolecular helicates
Publisher: Royal Society of Chemistry (RSC)
Date: 2001
DOI: 10.1039/B101970H
A new broad specificity alkaline metalloprotease from a Pseudomonas sp. isolated from refrigerated milk: Role of calcium in improving enzyme productivity
Publisher: Elsevier BV
Date: 03-2015
A 1H NMR Study of the Binding of Δ-[Ru(phen)2DPQ]2+ to the Hexanucleotide d(GTCGAC)2. Evidence for Intercalation from the Minor Groove
Publisher: American Chemical Society (ACS)
Date: 04-1997
DOI: 10.1021/JA962395L
Synthesis, characterisation and cytotoxicity of [(1,10-phenanthroline)(1R,2R,4R/1S,2S,4S)-4-methyl-1,2-cyclohexanediamine)platinum(II)]2+ (PHEN-4-MeDACH)
Publisher: Elsevier BV
Date: 02-2016
Synthesis, Characterisation, and Biological Activity of the Ruthenium Complexes of the N4-Tetradentate (N4-TL), 1,6-Di(2′-pyridyl)-2,5-dimethyl-2,5-diazahexane (picenMe2)
Publisher: CSIRO Publishing
Date: 2020
DOI: 10.1071/CH19528
Improved DNA equilibrium binding affinity determinations of platinum(ii) complexes using synchrotron radiation circular dichroism
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5AN00066A
Abstract: The DNA binding affinity of a range of Pt( ii ) complexes was reinvestigated using SRCD and a new method was implemented for determining the binding constant, saving time and minimising data collection.
Copper(II) and Palladium(II) Complexes with Cytotoxic and Antibacterial Activity
Publisher: CSIRO Publishing
Date: 2012
DOI: 10.1071/CH12058
Abstract: The synthesis of eight square pyramidal copper complexes with general structure [Cu(IL)(AL)H2O]2+, where IL represents various methylated 1,10-phenanthrolines, and AL represents either 1S,2S- or 1R,2R-diaminocyclohexane, is reported, with the complexes synthesised as both the perchlorate and chloride salts. The crystal structures of [Cu(1,10-phenanthroline)(1S,2S-diaminocyclohexane](ClO4)2·H2O and [Cu(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane](ClO4)2·1.5H2O are reported. Four square planar palladium complexes with general structure [Pd(IL)(AL)]Cl2 have also been synthesised. These complexes were synthesised in order to investigate the structure–activity relationship against both cancer cell lines and bacterial cultures. The copper complexes display anticancer activity similar to cisplatin and 1,10-phenanthroline (phen) in the L1210 murine leukaemia cell line. Methylation of the phen increased the copper complex cytotoxicity by approximately four-fold, compared with the non-methylated complex. No significant difference in activity was observed by altering the chirality of the diaminocyclohexane ligand. The copper complexes demonstrated antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli however, high levels of toxicity (30–60 % of death) were observed in the nematode Caenorhabditis elegans. The copper complexes have also been shown to act as DNA nucleases, with the ability to cleave plasmid DNA in the presence of hydrogen peroxide. The palladium complexes all have half maximal inhibitory concentration (IC50) values of ~10 μM in the L1210 cell line, with no significant difference in the cytotoxicity of any of the compounds tested. Minimal antibacterial activity of the palladium complexes was observed.
Self-Assembly of an Imidazolate-Bridged FeIII/CuII Heterometallic Cage
Publisher: American Chemical Society (ACS)
Date: 07-01-2014
DOI: 10.1021/IC402686S
Abstract: A rare, discrete, mixed-valent, heterometallic Fe(III)/Cu(II) cage, [Cu6Fe8L8](ClO4)12·χsolvent (H3L = tris{[2-{(imidazole-4-yl)methylidene}amino]ethyl}amine), was designed and synthesized via metal-ion-directed self-assembly with neutral tripodal metalloligands. The formation of this coordination cage was demonstrated by X-ray crystallography, ESI mass spectrometry, FT-IR, and UV-vis-NIR spectroscopy.
In vivo studies of a platinum(II) metallointercalator
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B811723C
Single TRAM domain RNA ‐binding proteins in A rchaea: functional insight from C tr3 from the A ntarctic methanogen M <
Publisher: Wiley
Date: 05-02-2016
Abstract: TRAM domain proteins present in Archaea and Bacteria have a β-barrel shape with anti-parallel β-sheets that form a nucleic acid binding surface a structure also present in cold shock proteins (Csps). Aside from protein structures, experimental data defining the function of TRAM domains is lacking. Here, we explore the possible functional properties of a single TRAM domain protein, Ctr3 (cold-responsive TRAM domain protein 3) from the Antarctic archaeon Methanococcoides burtonii that has increased abundance during low temperature growth. Ribonucleic acid (RNA) bound by Ctr3 in vitro was determined using RNA-seq. Ctr3-bound M. burtonii RNA with a preference for transfer (t)RNA and 5S ribosomal RNA, and a potential binding motif was identified. In tRNA, the motif represented the C loop a region that is conserved in tRNA from all domains of life and appears to be solvent exposed, potentially providing access for Ctr3 to bind. Ctr3 and Csps are structurally similar and are both inferred to function in low temperature translation. The broad representation of single TRAM domain proteins within Archaea compared with their apparent absence in Bacteria, and scarcity of Csps in Archaea but prevalence in Bacteria, suggests they represent distinct evolutionary lineages of functionally equivalent RNA-binding proteins.
Use of induced circular dichroism studies to predict the biological activity of platinum intercalators
Publisher: Elsevier BV
Date: 07-2003
Interaction of [Pt(en)(phen)]2+ and [Pt(en)(phi)]2+ with the Hexanucleotide d(GTCGAC)2: Evidence for Minor Groove Binding
Publisher: American Chemical Society (ACS)
Date: 25-08-2000
DOI: 10.1021/IC991488B
Combining the platinum(ii) drug candidate kiteplatin with 1,10-phenanthroline analogues
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7DT04108J
Abstract: Drug candidate kiteplatin has been combined with analogues of 1,10-phenanthroline, and the DNA affinity and cytotoxicity have been assessed.
The antimicrobial and antibiofilm activities of copper(II) complexes
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JINORGBIO.2014.07.012
Abstract: Biofilm-related bacterial infections pose a significant problem, as they are generally more tolerant to antibiotics and the immune system. Development of novel compounds with antibiofilm activity is therefore paramount. In this study we have analysed metal complexes of the general structure [M(IL)(AL)](2+) (where IL represents functionalised 1,10-phenanthrolines and AL represents 1S,2S- or 1R,2R-diaminocyclohexane) and [Cu(IL)3](2+). Antimicrobial activity was tested on a number of bacterial strains, showing that copper(II) compounds were active against both Gram-positive and Gram-negative bacteria, albeit that activity was generally higher for the former. The antibiofilm activity was then determined against a clinical isolate of meticillin-resistant Staphylococcus aureus (MRSA). Strikingly, the copper complexes tested showed significant activity against biofilms, and were better in the removal of biofilms than vancomycin, an antibiotic that is currently used in the treatment of MRSA infections.
Synthesis, characterization and in vitro and in vivo anticancer activity of Pt(iv ) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)]
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7DT01054K
Abstract: Synthesis and biological evaluation in vitro and in vivo of functionalized Pt( iv ) derivatives of Pt56MeSS.
N-Glycoside Complexes of Nickel(II); Probing Carbohydrate - Transition Metal Interactions
Publisher: CSIRO Publishing
Date: 2009
DOI: 10.1071/CH08349
Abstract: Nickel(ii) complexes prepared from d- and l-arabinose (d-ara and l-ara) and 1,2-diaminoethane (en), [Ni(en-d-ara)2](ClO4)2·2H2O 1 and [Ni(en-l-ara)2](ClO4)2·2H2O 2 (where en-d-ara is 1-((2-aminoethyl)amino)-1-deoxy-d-arabinose) were synthesized and characterized by absorption spectroscopy, circular dichroism (CD), and X-ray crystallography. The CD spectra of 1 and 2 in the d–d transition region indicate a C2 chiral configuration around the metal centre. X-ray crystallography of 1 revealed that two 1-((2-aminoethyl)amino)-1-deoxy-d-arabinose ligands coordinate to the nickel atom in nearly C2 symmetry, through the C(2) hydroxy group of the arabinose moiety and two nitrogen atoms of the diamine in a meridional mode. This results in a Λ-C2-helical configuration around the metal centre. The arabinose ring adopts the rare α-1C4 chair conformation and the carbohydrate–chelate ring conformation is δ.
Platinum Intercalators of DNA as Anticancer Agents
Publisher: Wiley
Date: 20-01-2017
Abstract: The drawbacks of the platinum chemotherapy agents cisplatin, carboplatin and oxaliplatin have inspired the development of compounds with different mechanisms of action. Polyaromatic platinum complexes (PPCs) are a promising anticancer alternative these bind reversibly with DNA through the insertion of a planar aromatic moiety between nucleobases in a process known as intercalation. PPCs have demonstrated in vitro behaviour remarkably different from that of cisplatin and exhibited cytotoxicity up to one hundred times higher than that of cisplatin in many cell lines. This microreview primarily discusses 1,10‐phenanthroline‐based complexes of the type [Pt(P L )(A L )] 2+ (where P L is a polyaromatic ligand and A L is an ancillary ligand), including their cytotoxicity, DNA‐binding behaviour and biological activity in vitro and in vivo. Other PPCs within the field, including dual‐mode DNA binders incorporating tethered acridines and other potently cytotoxic complexes, are also covered.
Photoactive and Luminescent Transition Metal Complexes as Anticancer Agents: A Guiding Light in the Search for New and Improved Cancer Treatments
Publisher: MDPI AG
Date: 03-2022
DOI: 10.3390/BIOMEDICINES10030578
Abstract: Cancer continues to be responsible for the deaths of more than 9 million people worldwide each year. Current treatment options are erse, but low success rates, particularly for those with late-stage cancers, continue to be a problem for clinicians and their patients. The effort by researchers globally to find alternative treatment options is ongoing. In the present study, we focused on innovations in inorganic anticancer therapies, specifically those with photoactive and luminescent properties. Transition metals offer distinct advantages compared to wholly organic compounds in both chemotherapeutics and luminescence properties. Here we report on the characteristics that result from discrete structural changes that have been expertly used to fine-tune their properties, and how erse inherent luminescent properties have been widely employed to monitor cellular localization to photodynamic therapy.
DNA as a target for antimicrobials
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.BIOORG.2014.03.009
Abstract: Resistance to antimicrobials is one of the biggest threats to our healthcare. However, in the last few decades very few truly novel antimicrobial compounds have been brought to market, creating the potential threat of a post-antibiotic era in which infections are very difficult to treat. Identification of novel compounds with antimicrobial activity is therefore paramount. Ideally, novel compounds should be designed that are active against targets that are not or barely used, as it is less likely that resistance already exists against such compounds. One ex le of an underexplored target in the treatment of infections is DNA. In this review we describe a number of DNA binding compounds and discuss potential opportunities and problems.
The synthesis and structural analysis of cis -β-{(1,6-di(2′-pyridyl)(2,5-dibenzyl-2,5-diazahexane O(1,2-diazahexane))(1,2-benzoquinone diimine))ruthenium(II)} and related complex
Publisher: Informa UK Limited
Date: 17-08-2007
Platinum(IV) Derivatives of [Pt(1S,2S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)] with Diclofenac Ligands in the Axial Positions: A New Class of Potent Multi-action Agents Exh
Publisher: American Chemical Society (ACS)
Date: 07-06-2023
Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based anticancer drugs
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.JINORGBIO.2008.11.014
Abstract: The use of anionic half-generation poly(amidoamine) dendrimers as drug delivery vehicles for [Pt(S,S-dach)(5,6-Me(2)phen)](2+) (56MESS) (where S,S-dach=1S,2S-diaminocyclohexane 5,6-Me(2)phen=5,6-dimethyl-1,10-phenanthroline) and [{Delta,Delta-Ru(phen)(2)}(2)(mu-bb7)](4+) (Rubb(7)) (where phen=1,10-phenanthroline bb7=1,7-bis[4-(4'-methyl-2,2'-bipyridyl)heptane]) has been studied by nuclear magnetic resonance spectroscopy. From one- and two-dimensional (1)H NMR spectra both 56MESS and Rubb(7) were found to bind to the surface of generation 3.5, 4.5, 5.5 and 6.5 dendrimers through electrostatic interactions. The higher charge and larger size of Rubb(7) resulted in stronger binding to all dendrimer generations (K(b)> or =2 x 10(5)M(-1)) compared with 56MESS (K(b)> or =1 x 10(4)M(-1)). Interestingly, there appeared to be no observable trend between dendrimer size and binding constant strength. The size of the free and 56MESS-bound dendrimers were examined using pulsed-gradient spin-echo NMR. The dendrimers ranged in hydrodynamic diameter from 11 to 20 nm and in all cases were larger than their corresponding full-generation dendrimer. Upon the addition of 56MESS the diameter of the dendrimers increased, consistent with surface binding.
Investigating the cytotoxicity of platinum(II) complexes incorporating bidentate pyridyl-1,2,3-triazole click ligands.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JINORGBIO.2016.06.017
Abstract: Six platinum(II) complexes of the type [Pt(P
Probing the Interactions of Cytotoxic [Pt(1S,2S‐DACH)(5,6‐dimethyl‐1,10‐phenanthroline)] and Its PtIV Derivatives with Human Serum
Publisher: Wiley
Date: 21-03-2017
Abstract: The discrepancy between the in vitro cytotoxic results and the in vivo performance of Pt56MeSS prompted us to look into its interactions and those of its Pt
Chemoselective Flow Hydrogenation Approaches to Diversify the Cytotoxic Tetrahydroepoxyisoindole Carboxamide Scaffold
Publisher: Wiley
Date: 07-02-2018
DNA Intercalators in Cancer Therapy: Organic and Inorganic Drugs and Their Spectroscopic Tools of Analysis
Publisher: Bentham Science Publishers Ltd.
Date: 06-2007
DOI: 10.2174/138955707780859413
Abstract: Since the discovery of the DNA intercalation process by Lerman in 1961 thousands of organic, inorganic octahedral (particularly ruthenium(II) and rhodium(III)) and square-planar (particularly platinum(II)) compounds have been developed as potential anticancer agents and diagnostic agents. The design and synthesis of new drugs is focused on bis-intercalators which have two intercalating groups linked via a variety of ligands, and synergistic drugs, which combine the anticancer properties of intercalation with other functionalities, such as covalent binding or boron-cages (for radiation therapy). Advances in spectroscopic techniques mean that the process of DNA intercalation can be examined in far greater detail than ever before, yielding important information on structure-activity relationships. In this review we examine the history and development of DNA intercalators as anticancer agents and advances in the analysis of DNA-drug interactions.
Synthesis of ruthenium-platinum Di- and Tri- nuclear complexes
Publisher: Elsevier BV
Date: 07-2003
The stereospecific synthesis of Λ-α-{dipyrido[3,2-a:2′3′-c](6,7,8,9-tetrahydro)phenazine[N,N′-di(2-picolyl)-2,5-dimethyl-2S,5S-diaminocyclohexane]ruthenium(ii)} and related β-isomers
Publisher: Royal Society of Chemistry (RSC)
Date: 2002
DOI: 10.1039/B208369H
Synthesis and Analysis of the Structure, Diffusion and Cytotoxicity of Heterocyclic Platinum(IV) Complexes.
Publisher: Wiley
Date: 06-10-2015
Abstract: We have developed six dihydroxidoplatinum(IV) compounds with cytotoxic potential. Each derived from active platinum(II) species, these complexes consist of a heterocyclic ligand (HL) and ancillary ligand (AL) in the form [Pt(HL)(AL)(OH)2](2+), where HL is a methyl-functionalised variant of 1,10-phenanthroline and AL is the S,S or R,R isomer of 1,2-diaminocyclohexane. NMR characterisation and X-ray diffraction studies clearly confirmed the coordination geometry of the octahedral platinum(IV) complexes. The self-stacking of these complexes was determined using pulsed gradient stimulated echo nuclear magnetic resonance. The self-association behaviour of square planar platinum(II) complexes is largely dependent on concentration, whereas platinum(IV) complexes do not aggregate under the same conditions, possibly due to the presence of axial ligands. The cytotoxicity of the most active complex, exhibited in several cell lines, has been retained in the platinum(IV) form.
The interactions of novel mononuclear platinum-based complexes with DNA
Publisher: Springer Science and Business Media LLC
Date: 12-2018
HPLC Separation of Diastereomeric Metal Complexes of the Form Δ,Λ-[Ru(diimine)2(S)-aminoacidate]
Publisher: CSIRO Publishing
Date: 2003
DOI: 10.1071/CH03072
Abstract: Complete separation of the photosensitive diastereomeric complexes of the general form [Ru(diimine)2(S)-aminoacidate], in which the diimine is 1,10-phenanthroline (phen) or 2,2′-bipyridine (bpy) and S-amino or N-methyl-S-aminoacidate are S-aspartate, S-tryptophanate or N-methyl-S-tryptophanate, has been achieved by reversed-phase ion-interaction chromatography. This has allowed the photo-equilibrated isomeric ratios for each complex to be estimated.
The structure-activity relationship of chiral square-planar platinum(II) metallointercalators
Publisher: Elsevier BV
Date: 07-2003
A Fluorine-18 Radiolabeling Method Enabled by Rhenium(I) Complexation Circumvents the Requirement of Anhydrous Conditions
Publisher: Wiley
Date: 11-04-2017
Abstract: Azeotropic distillation is typically required to achieve fluorine-18 radiolabeling during the production of positron emission tomography (PET) imaging agents. However, this time-consuming process also limits fluorine-18 incorporation, due to radioactive decay of the isotope and its adsorption to the drying vessel. In addressing these limitations, the fluorine-18 radiolabeling of one model rhenium(I) complex is reported here, which is significantly improved under conditions that do not require azeotropic drying. This work could open a route towards the investigation of a simplified metal-mediated late-stage radiofluorination method, which would expand upon the accessibility of new PET and PET-optical probes.
Synthesis of Flexible Bis‐Intercalating Ruthenium(II) Complexes
Publisher: Wiley
Date: 10-2007
Comparative analyses of cytotoxicity and molecular mechanisms between platinum metallointercalators and cisplatin
Publisher: Oxford University Press (OUP)
Date: 2012
DOI: 10.1039/C2MT20102J
Abstract: Platinum(II) metallointercalators of the type [Pt(I(L))(A(L))](2+), such as [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)](2+) (56MESS), are structurally different from cisplatin. This study, using a comparative transcriptomics approach, uncovered genomic expression patterns and molecular pathways that distinctively differentiated 56MESS and cisplatin in the eukaryote model organism Saccharomyces cerevisiae (yeast). Down-regulation of sulfur assimilation, cellular respiration, and energy metabolism were characteristics of 56MESS while up-regulation of these pathways and genes in cell cycle was the action of cisplatin. Furthermore, de novo purine biosynthesis and glycine metabolism were induced by 56MESS but suppressed by cisplatin. Different effects on intracellular concentrations of iron and copper were evident, with 56MESS more profoundly inducing genes controlling uptake of these ions than cisplatin. Finally, apart from 56MESS, additional metallointercalators including 56MEEN, 5MERR and 5MESS were subsequently identified to be more active in a cisplatin-resistant mouse leukaemia L1210cisR cell line than cisplatin, which provides multiple lead compounds for future drug development.
Synthesis, characterisation and potent cytotoxicity of unconventional platinum(iv ) complexes with modified lipophilicity
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9DT03339D
Abstract: Platinum( iv ) complexes with facile modulation of lipophilicity exhibited nanomolar activity against tested lines. The most potent complexes exhibited 850-fold greater activity than cisplatin against HT29 colon carcinoma with GI 50 values of 13 nM.
Probing the interaction of bisintercalating (2,2′:6′,2″-terpyridine)platinum(II) complexes with glutathione and rabbit plasma
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.JINORGBIO.2016.06.004
Abstract: Platinum(II) complexes have demonstrated considerable success in the treatment of cancer, but severe toxic side effects drive the search for new complexes with increased tumour selectivity and better efficacy. A critical concept that has to be considered in the context of designing novel Pt complexes is their interactions with biomolecules other than DNA. To this end, here the interactions of 16 previously reported bisintercalating (2,2':6',2″-terpyridine)platinum(II) complexes, [{Pt(terpy)}
The antimicrobial efficacy and DNA binding activity of some copper(II) complexes of 3,4,7,8-tetramethyl-1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline and 1,2-diaminocyclohexane
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.JINORGBIO.2016.06.006
Abstract: Four copper(II) complexes of the general structure [Cu(L
The synthesis, characterisation and cytotoxicity of bisintercalating (2,2′:6′,2′′-terpyridine)platinum(ii ) complexes
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4DT02773F
Abstract: Dinuclear (2,2′:6′,2′′-terpyridine)platinum( ii ) complexes were synthesised by tethering either thiol or pyridine based linkers. The cytotoxicity of the complexes was determined against human ovarian carcinoma cells (A2780) and its cisplatin-resistant sub-line A2780cis, as well as L1210 murine leukemia cells.
Cytotoxicity of a Series of Norcantharidin‐Inspired Tetrahydroepoxyisoindole Carboxamides
Publisher: Wiley
Date: 03-01-2017
Abstract: A series of 28 norcantharidin (NorC)-inspired analogues were accessed via a robust two-step Ugi intramolecular Diels-Alder (IMDA) sequence. Four analogues displayed whole-cell cytotoxicity equipotent to that of NorC and cisplatin against a number of cancer cell lines and a normal breast cell line (MCF10A). Notably, (3S,3aS,6R)-2-benzyl-7-methyl-N-(naphthalen-2-yl)-1-oxo-1,2,3,6-tetrahydro-3a,6-epoxyisoindole-3-carboxamide (trans-27) displayed superior whole-cell activity against breast (MCF-7, GI
Diffusion Coefficient of Cucurbit[ n ]urils ( n = 6 or 7) at Various Concentrations, Temperatures, and pH †
Publisher: American Chemical Society (ACS)
Date: 23-09-2009
DOI: 10.1021/JE800347U
Minor groove intercalation of Δ-[Ru(Me2phen)2dppz]2+ to the hexanucleotide d(GTCGAC)2
Publisher: Royal Society of Chemistry (RSC)
Date: 2002
DOI: 10.1039/B105689C
Improved curve fitting procedures to determine equilibrium binding constants
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B604686J
Abstract: For ligand-biomacromolecule titration experiments it has been traditional practice to extract parameters such as the equilibrium binding constant K and the number of bases per ligand binding site n with relatively labour intensive methods, usually based on single wavelength data, such as the difference method by Rodger and Nordén coupled together with a Scatchard plot. Presented in this paper are both the theory and a least squares fitting method to derive parameters such as K and n more directly from all spectral non-linear experimental data. Both the case of non competitive binding of a metal complex ligand to DNA and the case of displacement by a metal complex ligand of an ethidium marker attached to the DNA are considered. This work may be applied directly to reduce experimental data produced by a spectropolarimeter (for circular or linear dichroism) or a spectrophotometer (for fluorescence or UV-Vis spectroscopy).
A Systems Biology Approach to Understanding the Mechanisms of Action of an Alternative Anticancer Compound in Comparison to Cisplatin
Publisher: MDPI AG
Date: 10-11-2014
A comparison of the binding of metal complexes to duplex and quadruplex DNA
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B715458E
Abstract: Electrospray ionisation mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy were used to compare the binding of mononuclear nickel, ruthenium and platinum complexes to double stranded DNA (dsDNA) and quadruplex DNA (qDNA). CD studies provided evidence for the binding of intact complexes of all three metal ions to qDNA. ESI mass spectra of solutions containing platinum or ruthenium complexes and qDNA showed evidence for the formation of non-covalent complexes consisting of intact metal molecules bound to DNA. However, the corresponding spectra of solutions containing nickel complexes principally contained ions consisting of fragments of the initial nickel molecule bound to qDNA. In contrast ESI mass spectra of solutions containing nickel, ruthenium or platinum complexes and dsDNA only showed the presence of ions attributable to intact metal molecules bound to DNA. The fragmentation observed in mass spectral studies of solutions containing nickel complexes and qDNA is attributable to the lower thermodynamic stability of the former metal complexes relative to those containing platinum or ruthenium, as well as the slightly harsher instrumental conditions required to obtain spectra of qDNA. This conclusion is supported by the results of tandem mass spectral studies, which showed that ions consisting of intact nickel complexes bound to qDNA readily undergo fragmentation by loss of one of the ligands initially bound to the metal. The ESI-MS results also demonstrate that the binding affinity of each of the platinum and ruthenium complexes towards qDNA is significantly less than that towards dsDNA.
Target Biological Structures: The Cell, Organelles, DNA and RNA
Publisher: Springer Vienna
Date: 2011
Ruthenium Polypyridyl Metallointercalators
Publisher: Springer Vienna
Date: 2011
The Synthesis of Platinum(II) Intercalators
Publisher: Springer Vienna
Date: 2011
Platinum(II) Intercalating Complexes Based on 2,2′:6′,2″-Terpyridine
Publisher: Springer Vienna
Date: 2011
The effects of 56MESS on mitochondrial and cytoskeletal proteins and the cell cycle in MDCK cells
Publisher: Oxford University Press (OUP)
Date: 2013
DOI: 10.1039/C3MT00023K
Abstract: 56MESS has been shown to be cytotoxic but the mode of this action is unclear. In order to probe the mechanism of action for 56MESS, MDCK cells were utilised to investigate the effect on treated cells. IC50 values for 56MESS and cisplatin in the MDCK cell line, determined by a SRB assay, were 0.25 ± 0.03 and 18 ± 1.2 μM respectively. In a preliminary study, cells treated with 56MESS displayed no caspase-3/7 activity, suggesting that the mechanism of action is caspase independent. Protein expression studies revealed an increase the expression in the MTC02 protein associated with mitochondria in cells treated with 56MESS and cisplatin. Non-synchronised 56MESS-treated cells caused an arrest in the G2/M phase of the cell cycle, in comparison to the S phase arrest of cisplatin. In G0/G1 synchronised cells, both 56MESS and cisplatin both appeared to arrest within the S phase. these results suggest that 56MESS is capable of causing cell-cycle arrest, and that mitochondrial and cell cycle proteins may be involved in the mode of action of cytotoxicity of 56MESS.
Degradation of Bidentate-Coordinated Platinum(II)-Based DNA Intercalators by Reduced l -Glutathione
Publisher: American Chemical Society (ACS)
Date: 16-04-2008
DOI: 10.1021/JM7016072
Abstract: We have examined the interaction of [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] (2+) (1, 56MESS), [(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] (2+) (2, 5MESS), [(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)platinum(II)] (2+) (3, 56MERR), and [(5,6-dimethyl-1,10-phenanthroline)(ethylenediamine)platinum(II)] (2+) (4, 56MEEN) with reduced L-glutathione and L-methionine. Both thiols degrade all four complexes, mainly by displacing the ancillary ligand and forming a doubly bridged dinuclear complex. The degradation half-life of all the complexes with methionine is >7 days, indicating that these reactions are not biologically relevant. The rate of degradation by glutathione appears to be particularly important and shows an inverse correlation to cytotoxicity. The least active complex, 4 (t 1/2 glutathione: 20 h), degrades fastest, followed by 3 (31 h), 2 (40 h), and 1 (68 h). The major degradation product, [bis-mu-{reduced L-glutathione}bis{5,6-dimethyl-1,10-phenanthroline}bis{platinum(II)}] (2+) (5, 56MEGL), displays no cytotoxicity and is excluded as the source of the anticancer activity. Once bound by glutathione, these metal complexes do not then form coordinate bonds with guanosine. Partial encapsulation of the complexes within cucurbit[n]urils is able to stop the degradation process.
Identification of the molecular mechanisms underlying the cytotoxic action of a potent platinum metallointercalator.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2012
Polymers with platinum drugs and other macromolecular metal complexes for cancer treatment
Publisher: Elsevier BV
Date: 09-2014
Binding of the Δ- and Λ-Enantiomers of [Ru(dmphen)2dpq]2+ to the Hexanucleotide d(GTCGAC)2
Publisher: American Chemical Society (ACS)
Date: 11-1999
DOI: 10.1021/IC990092X
Abstract: 1H NMR spectroscopy and viscosity measurements have been used to study the oligonucleotide binding of the Delta- and Lambda-enantiomers of the metal complex [Ru(dmphen)(2)dpq](2+) (dmphen = 2,9-dimethyl-1,10-phenanthroline and dpq = dipyrido[3,2-f:2',3'-h]quinoxaline). The addition of either enantiomer to d(GTCGAC)(2) induced large upfield shifts and significant broadening for the hexanucleotide imino and metal complex dpq resonances. These data coupled with the observed increase in the melting transition midpoint of the hexanucleotide duplex upon addition of either enantiomer suggests that both Delta- and Lambda-[Ru(dmphen)(2)dpq](2+) bind by intercalation. A significant number of metal complex to hexanucleotide NOE contacts were observed in NOESY spectra of d(GTCGAC)(2) with added Delta- or Lambda-[Ru(dmphen)(2)dpq](2+). The observed intermolecular NOEs were consistent with both enantiomers intercalating between the G(4)A(5) bases of one strand and the T(2)C(3) bases of the complementary strand. Intermolecular NOEs from the dmphen protons were only observed to protons located in the hexanucleotide minor groove. Alternatively, NOE contacts from the dpq protons were observed to both major and minor groove protons. The NOE data suggest that the dpq ligand of the Delta-enantiomer intercalates deeply into the hexanucleotide base stack while the Lambda-enantiomer can only partially intercalate. Viscosity measurements were consistent with the proposed intercalation binding models. The addition of the Delta-enantiomer increased the relative viscosity of the DNA solution, while a decrease in the relative viscosity of the DNA was observed upon addition of the Lambda-metal complex. These results confirm our proposal that octahedral metallointercalators can intercalate from the minor groove. In addition, the results demonstrate that the left-handed enantiomer of [Ru(dmphen)(2)dpq](2+) prefers to intercalate from the narrow minor groove despite only being able to partially insert a polycyclic aromatic ligand into the DNA base stack.
Diffusion-based studies on the self-stacking and nanorod formation of platinum(ii) intercalators
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B820584A
Abstract: Pulsed gradient spin-echo nuclear magnetic resonance diffusion measurements have been used to show that platinum(II)-based intercalating agents self-stack in solution and form nanorods 0.45-3.9 nm in length (at 25 mM) their lengths are dependent on metal complex concentration, salt concentration and solution temperature.
The effect of ancillary ligand chirality and phenanthroline functional group substitution on the cytotoxicity of platinum(II)-based metallointercalators
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.JINORGBIO.2007.04.009
Abstract: Fifteen platinum(II)-based metallointercalators have been synthesised that utilise substituted 1,10-phenanthroline (phen) ligands, including 5-chloro-1,10-phenanthroline (5-Cl-phen), 5-methyl-1,10-phenanthroline (5-CH3-phen), 5-amino-1,10-phenanthroline (5-NH2-phen), 5-nitro-1,10-phenanthroline (5-NO2-phen) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and achiral ethylenediamine (en) and the chiral ancillary ligands 1S,2S-diaminocyclohexane (S,S-dach) and 1R,2R-diaminocyclohexane (R,R-dach). Their cytotoxicity in the L1210 murine leukaemia cell line was determined using growth inhibition assays. The most cytotoxic metal complexes are those that contain S,S-dach ancillary ligands and 5-CH3-phen intercalating ligands. One metallointercalator [Pt(5-CH3-phen)(S,S-dach)]Cl2 (5MESS), displays a 5-10-fold increase in cytotoxicity compared to the clinical agent cisplatin. From DNA binding experiments there appears to be no significant difference between any of the metal complexes, indicating that neither DNA binding affinity nor the mode of binding/DNA adduct formed is the sole determinant of the cytotoxicity of this family of platinum(II)-based metallointercalators.
Learning Discriminative Stein Kernel for SPD Matrices and Its Applications
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 05-2016
Isolation of Enantiomers of a Range of Tris(bidentate)ruthenium(II) Species Using Chromatographic Resolution and Stereoretentive Synthetic Methods
Publisher: Wiley
Date: 11-1998
DOI: 10.1002/(SICI)1099-0682(199811)1998:11<1677::AID-EJIC1677>3.0.CO;2-S
Quadruplex DNA-Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers
Publisher: Wiley
Date: 16-12-2201
Abstract: Four dinuclear terpyridineplatinum(II) (Pt-terpy) complexes were investigated for interactions with G-quadruplex DNA (QDNA) and duplex DNA (dsDNA) by synchrotron radiation circular dichroism (SRCD), fluorescent intercalator displacement (FID) assays and fluorescence resonance energy transfer (FRET) melting studies. Additionally, computational docking studies were undertaken to provide insight into potential binding modes for these complexes. The complexes demonstrated the ability to increase the melting temperature of various QDNA motifs by up to 17 °C and maintain this in up to a 600-fold excess of dsDNA. This study demonstrates that dinuclear Pt-terpy complexes stabilise QDNA and have a high degree of selectivity for QDNA over dsDNA.
195Pt NMR—theory and application
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B606190G
Abstract: This critical review highlights the progress in (195)Pt NMR over the last 25 years. In particular, some of the recent applications of (195)Pt NMR in catalytic and mechanistic studies, intermetallics and drug binding studies are discussed. (195)Pt NMR chemical shifts obtained from both theoretical studies and experiments are presented for Pt(0), Pt(II), Pt(III) and Pt(IV) complexes. (195)Pt coupling with various nuclei (viz. coupling constants) have also been collected in addition to data on (195)Pt relaxation. The latest developments in the theoretical knowledge and experimental advances have made (195)Pt NMR into a rich source of information in many fields. (164 references.).
Synthesis and Characterisation of Fluorescent Novel Pt(II) Cyclometallated Complexes with Anticancer Activity
Publisher: MDPI AG
Date: 28-04-2023
DOI: 10.3390/IJMS24098049
Abstract: Cancer poses a significant threat to global health and new treatments are required to improve the prognosis for patients. Previously, unconventional platinum complexes designed to incorporate polypyridyl ligands paired with diaminocyclohexane have demonstrated anticancer activity in KRAS mutated cells, previously thought to be undruggable and have cytotoxicity values up to 100 times better than cisplatin. In this work, these complexes were used as inspiration to design six novel cyclometallated ex les, whose fluorescence could be exploited to better understand the mechanism of action of these kinds of platinum drugs. The cytotoxicity results revealed that these cyclometallated complexes (CMCs) have significantly different activity compared to the complexes that inspired them they are as cytotoxic as cisplatin and have much higher selectivity indices in breast cancer cell lines (MCF10A/MCF-7). Complexes 1b, 2a, and 3b all had very high selectivity indexes compared to previous Pt(II) complexes. This prompted further investigation into their DNA binding properties, which revealed that they had good affinity to ctDNA, especially CMCs 1a and 3b. Their inherent fluorescence was successfully utilised in the calculation of their DNA binding affinity and could be useful in future work.
Spectroscopic investigations on the interactions of potent platinum(II) anticancer agents with bovine serum albumin
Publisher: Springer Science and Business Media LLC
Date: 11-05-2012
Back Cover: Quadruplex DNA‐Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers (Chem. Eur. J. 7/2016)
Publisher: Wiley
Date: 02-02-2016
DNA binding studies of ruthenium(II) dipyridotetrahydrophenazine complexes
Publisher: Elsevier BV
Date: 07-2003
Self-assembly of a unique 3d/4f heterometallic square prismatic box-like coordination cage
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6DT01651K
Abstract: A unique, slightly distorted square prismatic, box-like coordination cage of type [Cu 6 Dy 8 L 8 (MeOH) 8 (H 2 O) 6 ](NO 3 ) 12 · χ solvent has been synthesized via the supramolecular assembly between a non-centrosymmetric Dy( iii ) metalloligand and Cu( ii ) nitrate.
Multifaceted Studies of the DNA Interactions and In Vitro Cytotoxicity of Anticancer Polyaromatic Platinum(II) Complexes.
Publisher: Wiley
Date: 24-05-2016
Abstract: This study reports a detailed biophysical analysis of the DNA binding and cytotoxicity of six platinum complexes (PCs). They are of the type [Pt(PL )(SS-dach)]Cl2 , where PL is a polyaromatic ligand and SS-dach is 1S,2S-diaminocyclohexane. The DNA binding of these complexes was investigated using six techniques including ultraviolet and fluorescence spectroscopy, linear dichroism, synchrotron radiation circular dichroism, isothermal titration calorimetry and mass spectrometry. This portfolio of techniques has not been extensively used to study the interactions of such complexes previously each assay provided unique insight. The in vitro cytotoxicity of these compounds was studied in ten cell lines and compared to the effects of their R,R enantiomers activity was very high in Du145 and SJ-G2 cells, with some submicromolar IC50 values. In terms of both DNA affinity and cytotoxicity, complexes of 5,6-dimethyl-1,10-phenanthroline and 2,2'-bipyridine exhibited the greatest and least activity, respectively, suggesting that there is some correlation between DNA binding and cytotoxicity.
Antimicrobial activity of ruthenium-based intercalators
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.EJPS.2010.12.004
Abstract: Multidrug resistance of bacterial pathogens is a major problem and there is a clear need for the development of new types of antibiotics. Here we investigated the antimicrobial activity of ruthenium(II) based DNA-intercalating complexes. These complexes were found to have no activity in vitro against the Gram-negative bacterium Escherichia coli, but the complexes were clearly active against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. In vivo activity has also been demonstrated for one of the compounds using a simple infection model, the nematode Caenorhabditis elegans. Importantly, this also showed that the compound tested was not toxic to the nematodes.
Resolutely pure helices
Publisher: Springer Science and Business Media LLC
Date: 15-12-2011
DOI: 10.1038/NCHEM.1231
Kinetic and conformational properties of a novel T-cell antigen receptor transmembrane peptide in model membranes
Publisher: Wiley
Date: 2008
DOI: 10.1002/PSC.987
Abstract: Core peptide (CP GLRILLLKV) is a 9-amino acid peptide derived from the transmembrane sequence of the T-cell antigen receptor (TCR) alpha-subunit. CP inhibits T-cell activation both in vitro and in vivo by disruption of the TCR at the membrane level. To elucidate CP interactions with lipids, surface plasmon resonance (SPR) and circular dichroism (CD) were used to examine CP binding and secondary structure in the presence of either the anionic dimyristoyl-L-alpha-phosphatidyl-DL-glycerol (DMPG), or the zwitterionic dimyristoyl-L-alpha-phoshatidyl choline (DMPC). Using lipid monolayers and bilayers, SPR experiments demonstrated that irreversible peptide-lipid binding required the hydrophobic interior provided by a membrane bilayer. The importance of electrostatic interactions between CP and phospholipids was highlighted on lipid monolayers as CP bound reversibly to anionic DMPG monolayers, with no detectable binding observed on neutral DMPC monolayers.CD revealed a dose-dependent conformational change of CP from a dominantly random coil structure to that of beta-structure as the concentration of lipid increased relative to CP. This occurred only in the presence of the anionic DMPG at a lipid : peptide molar ratio of 1.6:1 as no conformational change was observed when the zwitterionic DMPC was tested up to a lipid : peptide ratio of 8.4 : 1.
Direct monitoring of spin transitions in a dinuclear triple-stranded helicate iron(ii ) complex through X-ray photoelectron spectroscopy
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7DT04190J
Abstract: VT-XPS shows that the spin behaviour is reversible between the HS and LS states in a new dinuclear helicate iron( ii ) complex.
A Quadruple-Action Platinum(IV) Prodrug with Anticancer Activity Against KRAS Mutated Cancer Cell Lines.
Publisher: Wiley
Date: 11-08-2017
Abstract: We developed a novel Pt
Supramolecular organization of protonated aminosilicones in water
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.JCIS.2013.07.010
Abstract: This study deals with the ionically-driven self-assembly of oligomeric aminosilicones, judiciously protonated with a variety of organic acids. Depending on the length of the silicone and the strength of the associated acids, (inverse) water-in-silicone emulsions, small nanoparticles, or catanionic vesicles were prepared and characterized by conventional (TEM) or original (DIC optical microscopy, DOSY NMR) techniques. For chains longer than about 40 units, a specific PEG-based sulfonic acid was synthesized and used to generate a supramolecular block-like copolymer and ensure fast and efficient emulsification. In all instances, a simple impulse such as pH increase triggered phase separation of the colloidal objects.
Cytotoxicity and Structural Analyses of 2,2′-Bipyridine-, 4,4′-Dimethyl-2,2′-bipyridine- and 2-(2′-Pyridyl)quinoxalineplatinum(II) Complexes
Publisher: Wiley
Date: 07-08-2015
(4,7-Dimethyl-1,10-phenanthroline)(ethylenediamine)platinum(II) dichloride tris(deuterium oxide) solvate
Publisher: International Union of Crystallography (IUCr)
Date: 31-10-2006
Drug Delivery Devices and Targeting Agents for Platinum(II) Anticancer Complexes
Publisher: CSIRO Publishing
Date: 2008
DOI: 10.1071/CH08157
Abstract: An ideal platinum-based delivery device would be one that selectively targets cancerous cells, can be systemically delivered, and is non-toxic to normal cells. It would be beneficial to provide drug delivery devices for platinum-based anticancer agents that exhibit high drug transport capacity, good water solubility, stability during storage, reduced toxicity, and enhanced anticancer activity in vivo. However, the challenges for developing drug delivery devices include carrier stability in vivo, the method by which extracellular or intracellular drug release is achieved, overcoming the various mechanisms of cell resistance to drugs, controlled drug release to cancer cells, and platinum drug bioavailability. There are many potential candidates under investigation including cucurbit[n]urils, cyclodextrins, calix[n]arenes, and dendrimers, with the most promising being those that are synthetically adaptable enough to attach to targeting agents.
Synthesis of a heterodinuclear ruthenium(II)-platinum(II) complex linked by l-cysteine methyl ester
Publisher: Elsevier BV
Date: 2007
Applications of Fluorescence Spectroscopy and Confocal Microscopy
Publisher: Springer Vienna
Date: 2011
3d transition metal complexes with a julolidine–quinoline based ligand: structures, spectroscopy and optical properties
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5QI00200A
Abstract: Five new complexes of a julolidine–quinoline based ligand with 3d transition metals have been synthesised and structurally characterised.
A continuous flow protocol to generate, regenerate, load, and recycle chlorotrityl functionalised resins
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8RE00318A
Abstract: From a screen of chlorinating agent concentration, flow rates, and reagent addition methodologies, a continuous flow protocol to activate, reactivate, and recycle both 2-chlorotrityl chloride functionalised polystyrene and trityl-hydroxy ChemMatrix functionalised resins was established.
Platinum coordination compounds with potent anticancer activity
Publisher: Elsevier BV
Date: 11-2018
A mixed-spin spin-crossover thiozolylimine [Fe
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9DT01947B
Abstract: The self-assembly of a mixed-spin [Fe
A 1H NMR Study of the DNA Binding of Ruthenium(II) Polypyridyl Complexes
Publisher: American Chemical Society (ACS)
Date: 30-05-1998
DOI: 10.1021/IC971194V
Synthesis and analysis of the anticancer activity of platinum(ii) complexes incorporating dipyridoquinoxaline variants
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4DT02133A
Abstract: Platinum complexes incorporating variants of dpq were synthesised. Their DNA affinity and cytotoxicity were compared to complexes containing phen variants, revealing unexpected trends in biological activity.
Potent Platinum(IV) Prodrugs That Incorporate a Biotin Moiety to Selectively Target Cancer Cells
Publisher: MDPI AG
Date: 12-12-2022
DOI: 10.3390/PHARMACEUTICS14122780
Abstract: Four platinum(IV) prodrugs incorporating a biotin moiety to selectively target cancer cells were synthesised, characterised, and their biological activity assessed. All complexes exhibited exceptional in vitro cytotoxicity against a panel of cancer cell lines, with [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(biotin)(hydroxido)](NO3)2, (2) exhibiting the lowest GI50 of 4 nM in the prostate Du145 cancer cell line. Each complex displayed significantly enhanced activity compared to cisplatin, with 2 being 1000-fold more active in the HT29 colon cancer cell line. Against the MCF-7 breast cancer cell line, in which high levels of biotin receptors are expressed, 2, [Pt(4,7-dimethoxy-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(biotin)(hydroxido)](NO3)2, (3), and [Pt(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(biotin)(hydroxido)](NO3)2, (4) exhibited enhanced activity compared to their platinum(II) cores, with 4 being 6-fold more active than its platinum(II) precursor. Furthermore, 3 exhibited 3-fold greater selectivity towards MCF-7 breast cancer cells compared to MCF10A breast healthy cells, and this was further confirmed by platinum uptake studies, which showed 3 to have almost 3-fold greater uptake in MCF-7 cells, compared to MCF10A cells. The results show that lipophilicity and selectivity both contributed to the cellular uptake of 1–4 however, this was not always translated to the observed cytotoxicity.
The cytotoxicity of some phenanthroline-based antimicrobial copper(II) and ruthenium(II) complexes
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JINORGBIO.2017.11.022
Abstract: The in vitro cytotoxic properties of antimicrobial copper(II) complexes with 3,4,7,8-tetramethyl-1,10-phenanthroline (TMP) or 4,7-dipyridyl-1,10-phenanthroline (DIP) ligands and ruthenium(II) complexes coordinated with TMP or 2,9-dimethyl-1,10-phenanthroline ligands were investigated. Both copper(II) complexes were found to have similar inhibitory concentrations (IC
Terpyridineplatinum(II) Incorporation in N‐Methylpyrrole‐Based Polyamides by Solid Phase Techniques
Publisher: Wiley
Date: 29-01-2009
The in vitro renal cell toxicity of some unconventional anticancer phenanthroline-based platinum(II) complexes
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.JINORGBIO.2017.11.021
Abstract: The cytotoxicity of platinum(II) complexes coordinated to a chiral diamine, 1S,2S-diaminocyclohexane or 1R,2R-diaminocyclohexane and 1,10-phenanthroline or 3,4,7,8-tetramethyl-1,10-phenanthroline has been investigated in the renal proximal tubule HK-2 cell line. All platinum(II) complexes exhibited lower cytotoxicity in HK-2 cells (IC
A Subset of New Platinum Antitumor Agents Kills Cells by a Multimodal Mechanism of Action Also Involving Changes in the Organization of the Microtubule Cytoskeleton
Publisher: American Chemical Society (ACS)
Date: 28-04-2019
DOI: 10.1021/ACS.JMEDCHEM.9B00489
Abstract: The substitution inert platinum agent [Pt(1 S,2 S-diaminocyclohexane)(5,6-dimethyl-1,10-phenanthroline)]
Evidence for chiral discrimination of ruthenium(ii) polypyridyl complexes by DNAElectronic supplementary information (ESI) available: absorption spectra. See http://www.rsc.org/suppdata/dt/b2/b208147d
Publisher: Royal Society of Chemistry (RSC)
Date: 10-12-2002
DOI: 10.1039/B208147D
A study of Pt(II)–phenanthroline complex interactions with double-stranded and G-quadruplex DNA by ESI–MS, circular dichroism, and computational docking
Publisher: Springer Science and Business Media LLC
Date: 26-03-2020
A Quadruple‐Action Platinum(IV) Prodrug with Anticancer Activity Against KRAS Mutated Cancer Cell Lines
Publisher: Wiley
Date: 11-08-2017
Synthesis and DNA binding of bisintercalating complexes of the type [(dpq)2Ru(phen-n-SOS-n-phen)Ru(dpq)2]4+
Publisher: Elsevier BV
Date: 07-2003
Platinum(II) intercalators as potential anti-cancer agents
Publisher: Elsevier BV
Date: 07-2003
Examination of Cucurbit[7]uril and Its Host−Guest Complexes by Diffusion Nuclear Magnetic Resonance
Publisher: American Chemical Society (ACS)
Date: 02-2008
DOI: 10.1021/JP709847P
Abstract: The self-diffusion of cucurbit[7]uril (CB[7]) and its host-guest complexes in D2O has been examined using pulsed gradient spin-echo nuclear magnetic resonance spectroscopy. CB[7] diffuses freely at a concentration of 2 mM with a diffusion coefficient (D) of 3.07 x 10(-10) m(2) s(-1). At saturation (3.7 mM), CB[7] diffuses more slowly (D = 2.82 x 10(-10) m(2) s(-1)) indicating that it partially self-associates. At concentrations between 2 and 200 mM, CsCl has no effect on the diffusion coefficient of CB[7] (1 mM). Conversely, CB[7] (2 mM) significantly affects the diffusion of 133Cs+ (1 mM), decreasing its diffusion coefficient from 1.86 to 0.83 x 10(-9) m(2) s(-1). Similar changes in the rate of diffusion of other alkali earth metal cations are observed upon the addition of CB[7]. The diffusion coefficient of 23Na+ changes from 1.26 to 0.90 x 10(-9) m(2) s(-1) and 7Li+ changes from 3.40 to 3.07 x 10(-9) m(2) s(-1). In most cases, encapsulation of a variety of inorganic and organic guests within CB[7] decreases their rates of diffusion in D2O. For instance, the diffusion coefficient of the dinuclear platinum complex trans-[[PtCl(NH3)2}2mu-dpzm](2+) (where dpzm is 4,4'-dipyrazolylmethane) decreases from 4.88 to 2.95 x 10(-10) m(2) s(-1) upon encapsulation with an equimolar concentration of CB[7].
Transition metal intercalators as anticancer agents-recent advances
Publisher: MDPI AG
Date: 31-10-2016
DOI: 10.3390/IJMS17111818
Cytotoxic platinum(ii ) intercalators that incorporate 1R,2R-diaminocyclopentane
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2DT31323E
Abstract: Twelve metallointercalators of the type [Pt(I(L))(A(L))](2+), where A(L) is either the R,R or S,S enantiomer of 1,2-diaminocyclopentane (DACP) and I(L) is either 1,10-phenathroline, 4-methyl-1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline or 3,4,7,8-tetramethyl-1,10-phenanthroline, were synthesised, characterised and the cytotoxicity to the L1210 cell line was determined. The crystal structures of PHENRRDACP and PHENSS were obtained as monoclinic with a space group of P2(1) (a/Å = 11.4966, b/Å = 6.6983, c/Å = 12.0235) and P2(1) (a/Å = 11.5777, b/Å = 7.0009, c/Å = 12.5079), respectively. The R,R enantiomer of 1,2-diaminocyclopentane (RRDACP) produced the most cytotoxic metallointercalators. The most cytotoxic metallointercalators were 56MERRDACP and 47MERRDACP with IC(50) values of 0.16 and 0.17 μM, respectively, in comparison to cisplatin (1 μM).
A mass spectrometric investigation of the ability of metal complexes to modulate transcription factor activity
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B904751D
Abstract: ESI mass spectrometry was used to assess the ability of metal complexes to inhibit binding of a transcription factor to a DNA molecule containing its recognition sequence.
A large spin-crossover [Fe4L4]8+ tetrahedral cage
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5TC00991J
Abstract: A large iron( ii ) tetrahedral cage displays temperature induced spin-crossover and liesst effects.
A mass spectrometric investigation of non-covalent interactions between ruthenium complexes and DNAElectronic supplementary information (ESI) available: Table S1: Assignments for ions observed in ESI mass spectra of reaction mixtures containing ruthenium compounds and DNA. Table S2: Assignments for ions observed in ESI mass spectra of reaction mixtures containing either daunomycin or distamycin, DNA and ruthenium compounds. See http://www.rsc.org/suppdata/dt/b4/b406889k/
Publisher: Royal Society of Chemistry (RSC)
Date: 2004
DOI: 10.1039/B406889K
Substituted β-cyclodextrin and calix[4]arene as encapsulatory vehicles for platinum(II)-based DNA intercalators
Publisher: American Chemical Society (ACS)
Date: 02-07-2008
DOI: 10.1021/IC800467C
Abstract: The encapsulation of three platinum(II)-based anticancer complexes, [(5,6-dimethyl-1,10-phenanthroline)(1 S,2 S-diaminocyclohexane)platinum(II)] (2+) ( 56MESS), [(5,6-dimethyl-1,10-phenanthroline)(1 R,2 R-diaminocyclohexane)platinum(II)] (2+) ( 56MERR), and [(5,6-dimethyl-1,10-phenanthroline)(ethylenediamine)platinum(II)] (2+) ( 56MEEN), with carboxylated-beta-cyclodextrin (c-beta-CD) and p-sulfonatocalix[4]arene (s-CX[4]) has been examined by one- and two-dimensional (1)H nuclear magnetic resonance (NMR) spectroscopy, pulsed gradient spin-echo NMR, ultraviolet spectrophotometry, glutathione degradation experiments, and growth inhibition assays. Titration of any of the three metal complexes with c-beta-CD resulted in 1:1 encapsulation complexes with the cyclodextrin located over the intercalating ligand of the metal complexes, with a binding constant of 10 (4)-10 (5) M (-1). In addition to binding over the phenanthroline ligand of 56MEEN, c-beta-CD was also found to portal bind to the ethylenediamine ligand, with fast exchange kinetics on the NMR timescale between the two binding sites. In contrast, the three metal complexes all formed 2:2 inclusion complexes with s-CX[4] where the two metal complexes stacked in a head-to-tail configuration and were capped by the s-CX[4] molecules. Interestingly, the 56MEEN-s-CX[4] complex appeared to undergo a thermodynamically controlled rearrangement to a less soluble complex over time. Encapsulation of the metal complexes in either c-beta-CD or s-CX[4] significantly decreased the metal complexes' rate of diffusion, consistent with the formation of larger particle volumes. Encapsulation of 56MESS within s-CX[4] or c-beta-CD protected the metal complex from degradation by reduced L-glutathione, with a reaction half-life greater than 9 days. In vitro growth inhibition assays using the LoVo human colorectal cancer cell line showed no significant change in the cytotoxicity of 56MESS when encapsulated by either s-CX[4] or c-beta-CD.
Synthesis and characterisation of metallopolyamide complexes
Publisher: Elsevier BV
Date: 12-2012
Advances in Platinum Chemotherapeutics
Publisher: Wiley
Date: 21-06-2010
Abstract: The approved platinum(II)-based anticancer agents cisplatin, carboplatin and oxaliplatin are widely utilised in the clinic, although with numerous disadvantages. With the aim of circumventing unwanted side-effects, a great deal of research is being conducted in the areas of cancer-specific targeting, drug administration and drug delivery. The targeting of platinum complexes to cancerous tissues can be achieved by the attachment of small molecules with biological significance. In addition, the administration of platinum complexes in the form of platinum(IV) allows for intracellular reduction to release the active form of the drug, cisplatin. Drug delivery includes such technologies as liposomes, dendrimers, polymers and nanotubes, with all showing promise for the delivery of platinum compounds. In this paper we highlight some of the recent advances in the field of platinum chemotherapeutics, with a focus on the technologies that attempt to utilise the cytotoxic nature of cisplatin, whilst improving drug targeting to reduce side-effects.
The synthesis of 2,3-diamino-2,3-dideoxy-α-D-glucose, 3,4-diamino-6hydroxymethyl-tetrahydro-pyran-2,5-diol and their chiral platinum compounds
Publisher: Elsevier BV
Date: 07-2003
Chiral metal complexes XLII. Reversed-phase high-performance liquid chromatographic separation of racemic dipeptides as their ternary Co(III) complexes with a chiral triamine
Publisher: Elsevier BV
Date: 02-1995
Novel Platinum(II) and Platinum(IV) Antitumor Agents that Exhibit Potent Cytotoxicity and Selectivity
Publisher: American Chemical Society (ACS)
Date: 08-12-2022
Exposing “bright” metals: Promising advances in photoactivated anticancer transition metal complexes
Publisher: Bentham Science Publishers Ltd.
Date: 12-02-2018
DOI: 10.2174/0929867324666170530085123
Abstract: Photodynamic therapy (PDT) is an increasingly prominent field in anticancer research. PDT agents are typically nontoxic in the absence of light and can be stimulated with nonionising irradiation to “activate” their cytotoxic effect. Photosensitzers are not classified as chemotherapy drugs although it is advantageous to control the toxicity of a drug through localised irradiation allowing for selective treatment. Transition metals are an extremely versatile class of compounds with various unique properties such as oxidation state, coordination number, redox potential and molecular geometry that can be tailored for specific uses. This makes them excellent PDT candidates as their properties can be manipulated to absorb a specific range of light wavelengths, cross cellular membranes or target specific sites in vitro. This article reviews recent advances in transition metal PDT agents, with a focus on structural scaffolds from which several metal complexes in a series are synthesised, as well as their in vitro cytotoxicity in the presence or absence of irradiation. The success of clinical photoactive agents such as Photofrin® has inspired the development of thousands of potential PDT agents. Transition metal complexes in particular have demonstrated excellent versatility and ersity when it comes to PDT for treatment of invasive cancers. This review has highlighted some of the many recent advances of transition metal PDT agents with high in vitro and in vivo phototoxic activity. Photoactive transition metal complexes have proven their potential due to their inherent physicochemical variety, allowing them to fill a niche in the PDT world.
A flow-based transition-metal-catalysed hydrogenolysis strategy to facilitate peptide side-chain deprotection
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1OB02179F
Abstract: A palladium-catalysed flow chemistry protocol to selectively mediate N β side-chain Cbz-lysis from extended peptide sequences in the presence of trityl, t -butyl and N α -Fmoc protecting groups.
Dinuclear ruthenium complexes as sequence- and structure-selective binding agents for DNA
Publisher: Elsevier BV
Date: 07-2003
Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates
Publisher: MDPI AG
Date: 21-10-2022
DOI: 10.3390/MOLECULES27207120
Abstract: A new series of cytotoxic platinum(IV) complexes (1–8) incorporating halogenated phenylacetic acid derivatives (4-chlorophenylacetic acid, 4-fluorophenylacetic acid, 4-bromophenylacetic acid and 4-iodophenylacetic acid) were synthesised and characterised using spectroscopic and spectrometric techniques. Complexes 1–8 were assessed on a panel of cell lines including HT29 colon, U87 glioblastoma, MCF-7 breast, A2780 ovarian, H460 lung, A431 skin, Du145 prostate, BE2-C neuroblastoma, SJ-G2 glioblastoma, MIA pancreas, the ADDP-resistant ovarian variant, and the non-tumour-derived MCF10A breast line. The in vitro cytotoxicity results confirmed the superior biological activity of the studied complexes, especially those containing 4-fluorophenylacetic acid and 4-bromophenylacetic acid ligands, namely 4 and 6, eliciting an average GI50 value of 20 nM over the range of cell lines tested. In the Du145 prostate cell line, 4 exhibited the highest degree of potency amongst the derivatives, displaying a GI50 value of 0.7 nM, which makes it 1700-fold more potent than cisplatin (1200 nM) and nearly 7-fold more potent than our lead complex, 56MESS (4.6 nM) in this cell line. Notably, in the ADDP-resistant ovarian variant cell line, 4 (6 nM) was found to be almost 4700-fold more potent than cisplatin. Reduction reaction experiments were also undertaken, along with studies aimed at determining the complexes’ solubility, stability, lipophilicity, and reactive oxygen species production.
Symmetrical dinuclear complexes with high DNA affinity based on [Ru(dpq)2(phen)]2+Electronic supplementary information (ESI) available: method for determining equilibrium binding constants and represe
Publisher: Royal Society of Chemistry (RSC)
Date: 2004
DOI: 10.1039/B316917K
Abstract: Symmetrical homometallic dinuclear complexes of the type [(Ru(dpq)2)2(phen-SOS-phen)]4+, with a flexible 2-mercaptoethyl ether linker joining the two [Ru(dpq)2(phen)]2+-based sub-units, have DNA dissociation constants (Kd) in the nM range.
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