ORCID Profile
0000-0002-6584-0516
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
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)
Theoretical and Computational Chemistry | Atomic And Molecular Physics | Civil engineering | Atomic, Molecular, Nuclear, Particle and Plasma Physics | Physical Chemistry Not Elsewhere Classified | Physical chemistry not elsewhere classified | Biological And Medical Chemistry | Radiation and Matter | Quantum Chemistry | Quantum Chemistry | Infrastructure engineering and asset management | Construction materials | Atomic and Molecular Physics
ANZSRC Socio-Economic Objective (SEO)
Chemical sciences | Physical sciences | Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Physical Sciences | Biological sciences |
Related Links
Publications
Methylation of zebularine investigated using density functional theory calculations
Publisher: Wiley
Date: 03-05-2011
DOI: 10.1002/JCC.21785
Abstract: Deoxyribonucleic acid (DNA) methylation is an epigenetic phenomenon, which adds methyl groups into DNA. This study reveals methylation of a nucleoside antibiotic drug 1-(β-D-ribofuranosyl)-2-pyrimidinone (zebularine or zeb) with respect to its methylated analog, 1-(β-D-ribofuranosyl)-5-methyl-2-pyrimidinone (d5) using density functional theory calculations in valence electronic space. Very similar infrared spectra suggest that zeb and d5 do not differ by types of the chemical bonds, but distinctly different Raman spectra of the nucleoside pair reveal that the impact caused by methylation of zeb can be significant. Further valence orbital-based information details on valence electronic structural changes caused by methylation of zebularine. Frontier orbitals in momentum space and position space of the molecules respond differently to methylation. Based on the additional methyl electron density concentration in d5, orbitals affected by the methyl moiety are classified into primary and secondary contributors. Primary methyl contributions include MO8 (57a), MO18 (47a), and MO37 (28a) of d5, which concentrates on methyl and the base moieties, suggest certain connection to their Frontier orbitals. The primary and secondary methyl affected orbitals provide useful information on chemical bonding mechanism of the methylation in zebularine.
Mechanistic Insights into Direct Methane Oxidation to Methanol on Single-Atom Transition-Metal-Modified Graphyne
Publisher: American Chemical Society (ACS)
Date: 12-11-2021
Experimental and Theoretical Soft X-ray Study of Nicotine and Related Compounds
Publisher: American Chemical Society (ACS)
Date: 27-04-2020
Positron scattering from chiral enantiomers
Publisher: American Physical Society (APS)
Date: 22-05-2012
The electronic structure of bicyclo[2.2.2]octa-2,5-dione
Publisher: Elsevier BV
Date: 10-2020
Inner-shell chemical shift of DNA/RNA bases and inheritance from their parent purine and pyrimidine
Publisher: International Union of Crystallography (IUCr)
Date: 03-10-2008
An electron momentum spectroscopy and density functional theory study of the outer valence electronic structure of stella-2,6-dione
Publisher: IOP Publishing
Date: 07-07-2003
Modulated Charge Injection in p-Type Dye-Sensitized Solar Cells Using Fluorene-Based Light Absorbers
Publisher: American Chemical Society (ACS)
Date: 26-02-2014
DOI: 10.1021/AM405610B
Electronic Structure of the Azide Group in 3¢-Azido-3¢-deoxythymidine (AZT) Compared to Small Azide Compounds
Publisher: MDPI AG
Date: 22-07-2009
Throughput based temporal verification for monitoring large batch of parallel processes
Publisher: ACM
Date: 26-05-2014
A study of aliphatic amino acids using simulated vibrational circular dichroism and Raman optical activity spectra
Publisher: Springer Science and Business Media LLC
Date: 11-2013
Valence structures of aromatic bioactive compounds: a combined theoretical and experimental study
Publisher: International Union of Crystallography (IUCr)
Date: 12-07-2012
Erratum to Orbital based electronic structural signatures of the guanine keto G-7H/G-9H tautomer pair as studied using dual space analysis [Biophys. Chem. 121 (2006) 105-120] (DOI:10.1016/j.bpc.2005.12.006)
Publisher: Elsevier BV
Date: 02-2007
Structural impact on the methano bridge in norbornadiene, norbornene and norbornane
Publisher: Elsevier BV
Date: 12-2004
Logistics scheduling based on cloud business workflows
Publisher: IEEE
Date: 05-2014
Electronic structure and intramolecular interactions in three methoxyphenol isomers
Publisher: AIP Publishing
Date: 05-10-2018
DOI: 10.1063/1.5048691
Abstract: Electronic structures and intramolecular interactions of three methoxyphenol positional isomers and their rotamers have been studied using core X-ray photoelectron spectroscopy and quantum mechanical calculations. The structural calculations are benchmarked against published calculations of enthalpy of formation and rotational constants, and published experimental data. The good agreement obtained confirms the accuracy of the results. A single rotamer of each isomer was then selected and the C 1s photoelectron spectra calculated and compared with experiment. Good agreement is obtained, and the calculations were extended to investigate the effects of conformation. For 3-methoxyphenol, the difference in the C 1s binding energy of the conformers is small, & .15 eV. For 2-methoxyphenol, whose ground state includes an OH⋯OCH3 hydrogen bond, the higher energy rotamers show the largest shifts for the methyl carbon atom, whereas the ring carbon bonded to OH hardly shifts The theoretical differences in core level energies of the two rotamers of 4-MP are still smaller, & .05 eV. By comparing calculations neglecting or including final state relaxation upon ionization, the relaxation energy of the phenyl carbons in all isomers is found to be ∼0.5 eV, while that of the methyl groups is ∼1.3 eV.
Positional and Conformational Isomerism in Hydroxybenzoic Acid: A Core-Level Study and Comparison with Phenol and Benzoic Acid
Publisher: American Chemical Society (ACS)
Date: 09-11-2021
Structures of Cycloserine and 2-Oxazolidinone Probed by X-ray Photoelectron Spectroscopy: Theory and Experiment
Publisher: American Chemical Society (ACS)
Date: 12-05-2014
DOI: 10.1021/JP500308J
Abstract: The electronic structures and properties of 2-oxazolidinone and the related compound cycloserine (CS) have been investigated using theoretical calculations and core and valence photoelectron spectroscopy. Isomerization of the central oxazolidine heterocycle and the addition of an amino group yield cycloserine. Theory correctly predicts the C, N, and O 1s core spectra, and additionally, we report theoretical natural bond orbital (NBO) charges. The valence ionization energies are also in agreement with theory and previous measurements. Although the lowest binding energy part of the spectra of the two compounds shows superficial similarities, further analysis of the charge densities of the frontier orbitals indicates substantial reorganization of the wave functions as a result of isomerization. The highest occupied molecular orbital (HOMO) of CS shows leading carbonyl π character with contributions from other heavy (non-H) atoms in the molecule, while the HOMO of 2-oxazolidinone (OX2) has leading nitrogen, carbon, and oxygen pπ characters. The present study further theoretically predicts bond resonance effects of the compounds, evidence for which is provided by our experimental measurements and published crystallographic data.
Toward rational design of organic dye sensitized solar cells (DSSCs): An application to the TA-St-CA dye
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JMGM.2012.12.005
Abstract: A computer aided rational design has been performed on TA-St-CA dye sensitizer in order to improve the desirable properties for new organic dye sensitized solar cell (DSSC). A number of electron-donating (ED) and electron-withdrawing (EW) units based on Dewar's rules are substituted into the π-conjugated oligo-phenylenevinylene bridge of the reference TA-St-CA dye. The effects of these alternations on the molecular structures and the electron absorption spectra are calculated using time-dependant density functional theory (TDDFT). It is found that chemical modifications using electron donating (ED) substitutions exhibit advantages over the electron withdrawing (EW) substitutes to reduce the HOMO-LUMO energy gap as well as the electron distribution of the frontier orbitals of the new dyes. Dewar's rule is a useful guideline for rational design of new dye sensitizers with desired HOMO-LUMO gap. The impact on the optical spectra of new dyes are, however, less significant.
Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents
Publisher: Informa UK Limited
Date: 13-02-2013
DOI: 10.3109/14756366.2013.765417
Abstract: Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 4' position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 μM, respectively, and with IC50 equal to 3.98 and 1.04 μM on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 μM, respectively.
Theoretical Investigation of Single and Double Transition Metals Anchored on Graphyne Monolayer for Nitrogen Reduction Reaction
Publisher: American Chemical Society (ACS)
Date: 18-06-2020
A facile MnSO4 surface coated NiMnFeOx catalyst with enhanced SO2 resistance for SCR reaction: A dual-protection mechanism
Publisher: Elsevier BV
Date: 03-2024
Fine Tuning of Fluorene-Based Dye Structures for High-Efficiency p-Type Dye-Sensitized Solar Cells
Publisher: American Chemical Society (ACS)
Date: 24-06-2014
DOI: 10.1021/AM5022396
Abstract: We report on an experimental study of three organic push-pull dyes (coded as zzx-op1, zzx-op1-2, and zzx-op1-3) featuring one, two, and three fluorene units as spacers between donors and acceptors for p-type dye-sensitized solar cells (p-DSSC). The results show increasing the number of spacer units leads to obvious increases of the absorption intensity between 300 nm and 420 nm, a subtle increase in hole driving force, and almost the same hole injection rate from dyes to NiO nanoparticles. Under optimized conditions, the zzx-op1-2 dye with two fluorene spacer units outperforms other two dyes in p-DSSC. It exhibits an unprecedented photocurrent density of 7.57 mA cm(-2) under full sun illumination (simulated AM 1.5G light illumination, 100 mW cm(-2)) when the I(-)/I3(-) redox couple and commercial NiO nanoparticles were used as an electrolyte and a semiconductor, respectively. The cells exhibited excellent long-term stability. Theoretical calculations, impedance spectroscopy, and transient photovoltage decay measurements reveal that the zzx-op1-2 exhibits lower photocurrent losses, longer hole lifetime, and higher photogenerated hole density than zzx-op1 and zzx-op1-3. A dye packing model was proposed to reveal the impact of dye aggregation on the overall photovoltaic performance. Our results suggest that the structural engineering of organic dyes is important to enhance the photovoltaic performance of p-DSSC.
Solvatochromism and linear solvation energy relationship of the kinase inhibitor SKF86002
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.SAA.2016.07.027
Abstract: We studied the spectroscopic characteristics of SKF86002, an anti-inflammatory and tyrosine kinase inhibitor drug candidate. Two conformers SKF86002A and SKF86002B are separated by energy barriers of 19.68kJ·mol(-1) and 6.65kJ·mol(-1) due to H-bonds, and produce the three major UV-Vis absorption bands at 325nm, 260nm and 210nm in cyclohexane solutions. This environment-sensitive fluorophore exhibited emission in the 400-500nm range with a marked response to changes in environment polarity. By using twenty-two solvents for the solvatochromism study, it was noticed that solvent polarity, represented by dielectric constant, was well correlated with the emission wavelength maxima of SKF86002. Thus, the SKF86002 fluorescence peak red shifted in aprotic solvents from 397.5nm in cyclohexane to 436nm in DMSO. While the emission maximum in hydrogen donating solvents ranged from 420nm in t-butanol to 446nm in N-methylformamide. Employing Lippert-Mataga, Bakhshiev and Kawski models, we found that one linear correlation provided a satisfactory description of polarity effect of 18 solvents on the spectral changes of SKF86002 with R(2) values 0.78, 0.80 and 0.80, respectively. Additionally, the multicomponent linear regression analysis of Kamlet-Taft (R(2)=0.94) revealed that solvent acidity, basicity and polarity accounted for 31%, 24% and 45% of solvent effects on SKF86002 emission, respectively. While Catalán correlation (R(2)=0.92) revealed that solvatochromic change of SKF86002 emission was attributed to changes in solvent dipolarity (71%), solvent polarity (12%), solvent acidity (11%) and solvent basicity (6%). Plot of Reichardt transition energies and emission energies of SKF86002 in 18 solvents showed also a linear correlation with R(2)=0.90. The dipole moment difference between excited and ground state was calculated to be 3.4-3.5debye.
Assessment of new anti-HER2 ligands using combined docking, QM/MM scoring and MD simulation
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JMGM.2012.12.001
Abstract: In the development of new anti-cancer drugs to tackle the problem of resistance to current chemotherapeutic agents, a new series of anti-HER2 (human epidermal growth factor receptors 2) agents has been synthesized and investigated using different computational methods. Although non-selective, the most active inhibitor in the new series shows higher activity toward HER2 than EGFR. The induced fit docking protocol (IFD) is performed to find possible binding poses of the new inhibitors in the active site of the HER2 receptor. Molecular dynamic simulations of the inhibitor-protein complexes for the two most active compounds from the new series are carried out. Simulations stability is checked using different stability parameters. Different scoring functions are employed.
Photoelectron spectra and structures of three cyclic dipeptides: PhePhe, TyrPro, and HisGly
Publisher: AIP Publishing
Date: 22-03-2012
DOI: 10.1063/1.3693763
Abstract: We have investigated the electronic structure of three cyclic dipeptides: cyclo(Histidyl-Glycyl) (cHisGly), cyclo(Tyrosyl-Prolyl) (cTyrPro), and cyclo(Phenylalanyl-Phenylalanyl) (cPhePhe) in the vapor phase, by means of photoemission spectroscopy and theoretical modeling. The last compound was evaporated from the solid linear dipeptide, but cyclised, losing water to form cPhePhe in the gas phase. The results are compared with our previous studies of three other cyclopeptides. Experimental valence and core level spectra have been interpreted in the light of calculations to identify the basic chemical properties associated with the central diketopiperazine ring, and with the additional functional groups. The valence spectra are generally characterized by a restricted set of outer valence orbitals separated by a gap from most other valence orbitals. The theoretically simulated core and valence spectra of all three cyclic dipeptides agree reasonably well with the experimental spectra. The central ring and the side chains act as independent chromophores whose spectra do not influence one another, except for prolyl dipeptides, where the pyrrole ring is fused with the central ring. In this case, significant changes in the valence and core level spectra were observed, and explained by stronger hybridization of the valence orbitals.
The d-electrons of Fe in ferrocene: the excess orbital energy spectrum (EOES)
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4RA14506B
Abstract: The EOES (Δ ε i = ε E-Fci − ε S-Fci) shows that the orbitals with significantly excess energies are Fe d-electron dominant.
Photoelectron Spectra of Some Antibiotic Building Blocks: 2-Azetidinone and Thiazolidine-Carboxylic Acid
Publisher: American Chemical Society (ACS)
Date: 17-07-2012
DOI: 10.1021/JP302950Y
Abstract: X-ray photoelectron spectra of the core and valence levels of the fundamental building blocks of β-lactam antibiotics have been investigated and compared with theoretical calculations. The spectra of the compounds 2-azetidinone and the 2- and 4-isomers of thiazolidine-carboxylic acid are interpreted in the light of theoretical calculations. The spectra of the two isomers of thiazolidine-carboxylic acid are rather similar, as expected, but show clear effects due to isomerization. Both isomers are analogues of proline, which is well-known to populate several low energy conformers in the gas phase. We have investigated the low energy conformers of thiazolidine-4-carboxylic acid theoretically in more detail and find some spectroscopic evidence that multiple conformers may be present. The measured valence levels are assigned for all three compounds, and the character of the frontier orbitals is identified and analyzed.
Exploring the optical reporting characteristics of drugs: UV-Vis spectra and conformations of the tyrosine kinase inhibitor SKF86002
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NJ03361C
Abstract: The ultimate understanding of drug–protein interactions relies on understanding drug behaviours in solution, at the molecular level.
Impact of ketone and amino on the inner shell of guanine
Publisher: International Union of Crystallography (IUCr)
Date: 19-05-2009
Comparative genomics of pathogens
Publisher: Springer New York
Date: 03-10-2010
Solvent effects on blue shifted improper hydrogen bond of C–H⋯O in deoxycytidine isomers
Publisher: Elsevier BV
Date: 11-2010
Cover Image, Volume 120, Issue 23
Publisher: Wiley
Date: 28-10-2020
DOI: 10.1002/QUA.26513
Molecular dynamics study of ferrocene topology under various temperatures
Publisher: Wiley
Date: 04-08-2020
DOI: 10.1002/QUA.26398
A photoelectron spectroscopic investigation of aspirin, paracetamol and ibuprofen in the gas phase
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2CP05810C
Abstract: We have investigated the electronic structure of isolated molecules of paracetamol, aspirin and ibuprofen using computational methods and benchmarked the results against valence and core photoelectron spectra.
Graphene oxide nanoparticles for enhanced photothermal cancer cell therapy under the irradiation of a femtosecond laser beam
Publisher: Wiley
Date: 10-08-2013
DOI: 10.1002/JBM.A.34871
Abstract: Nano-sized graphene and graphene oxide (GO) are promising for biomedical applications, such as drug delivery and photothermal therapy of cancer. It is observed in this work that the ultrafast reduction of GO nanoparticles (GONs) with a femtosecond laser beam creates extensive microbubbling. To understand the surface chemistry of GONs on the microbubble formation, the GONs were reduced to remove most of the oxygen-containing groups to get reduced GONs (rGONs). Microbubbling was not observed when the rGONs were irradiated by the laser. The instant collapse of the microbubbles may produce microcavitation effect that brings about localized mechanical damage. To understand the potential applications of this phenomenon, cancer cells labeled with GONs or rGONs were irradiated with the laser. Interestingly, the microbubbling effect greatly facilitated the destruction of cancer cells. When microbubbles were produced, the effective laser power was reduced to less than half of what is needed when microbubbling is absent. This finding will contribute to the safe application of femtosecond laser in the medical area by taking advantage of the ultrafast reduction of GONs. It may also find other important applications that need highly localized microcavitation effects.
NMR Chemical Shift and Methylation of 4-Nitroimidazole: Experiment and Theory
Publisher: CSIRO Publishing
Date: 2021
DOI: 10.1071/CH20199
Abstract: Nitroimidazoles and derivatives are a class of active pharmaceutical ingredients (APIs) first introduced sixty years ago. As anti-infection agents, the structure–activity relationships of nitroimidazole compounds have been particularly difficult to study due to their low reduction potentials and unique electronic structures. In this study, we combine dynamic nuclear polarization (DNP)-enhanced solid-state (100K), solid-state (298K), and 1H-13C heteronuclear single quantum coherence (HSQC) solution-state NMR techniques (303K) with density functional theory (DFT) to study the 1H, 13C, and 15N chemical shifts of 4-nitroimidazole (4-NI) and 1-methyl-4-nitroimidazole (CH3-4NI). The 4-NI chemical shifts were observed at 119.4, 136.4, and 144.7ppm for 13C, and at 181.5, 237.4, and 363.0ppm for 15N. The measurements revealed that methylation (deprotonation) of the amino nitrogen N(1) of 4-NI had less effect (Δδ=−4.8ppm) on the N(1) chemical shift but was compensated by shielding of the N(3) (Δδ=11.6ppm) in CH3-4NI. The calculated chemical shifts using DFT for 4-NI and CH3-4NI agreed well with the experimental values (within 2%) for the imidazole carbons. However, larger discrepancies (up to 13%) were observed between the calculated and measured 15N NMR chemical shifts for the imidazole nitrogen atoms of both molecules, which indicate that effects such as imidazole ring resonant structures and molecular dynamics may also contribute to the nitrogen chemical environment.
In silico design: Extended molecular dynamic simulations of a new series of dually acting inhibitors against EGFR and HER2
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JMGM.2013.06.004
Abstract: Based on the hit structures that have been identified in our previous studies against EGFR and HER2, new potential inhibitors that share the same scaffold of the hit structures are designed and screened in silico. Insights into understanding the potential inhibitory effect of the new inhibitors against both EGFR and HER2 receptors is obtained using extended molecular dynamics (MD) simulations and different scoring techniques. The binding mechanisms and dynamics are detailed with respect to two approved inhibitors against EGFR (lapatinib) and HER2 (SYR127063). The best scoring inhibitor (T9) is chosen for additional in silico investigation against both the wild-type and T790M mutant strain of EGFR and the wild-type HER2. The results reveal that certain substitution patterns increase the stability and assure stronger binding and higher H-bond occupancy of the conserved water molecule that is commonly observed with kinase crystal structures. Furthermore, the new inhibitor (T9) forms stable interactions with the mutant strain as a direct consequence of the enhanced ability to form additional hydrogen bonding interactions with binding site residues.
Optical spectra and conformation pool of tyrosine kinase inhibitor PD153035 using a robust quantum mechanical conformation search
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1NJ04348J
Abstract: The most potent drug configuration is not necessarily the lowest energy conformer. The optical spectral profile of a flexible TKI depends on the distribution of the conformers and therefore the conditions such as environment (solvent).
Resveratrol's Hidden Hand: A Route to the Optical Detection of Biomolecular Binding
Publisher: American Chemical Society (ACS)
Date: 17-02-2018
Abstract: Resveratrol is a stilbenoid phytoalexin with promising myriad health benefits predominantly contributed by the trans ( E) diastereomeric form. A recent study has implicated the cis ( Z) diastereomer in human health. This stereoisomer binds with high affinity to human tyrosyl-tRNA synthetase, initiating a downstream cascade that promotes the expression of genes associated with the cellular stress response. We discovered that the nonplanar structure of the cis-resveratrol conformer possesses certain chiral signals in its simulated vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra. These features may be used for the optical detection of the binding event and in understanding the more ersified biological roles of trans-resveratrol over cis-resveratrol. We use a density functional theory model, which is validated against the known results for the E diastereomer. The Z diastereomer is significantly nonplanar and can exist in two helical atropisomeric forms. These forms exchange rapidly in solution, but only one is observed to bind with the synthetase. This suggests that the binding may generate an enantiomeric excess, leading to detectable changes in the vibrational optical activity spectra. We identify candidate features at 998, 1649, and 1677 cm
Evaluation and outlook for Australian renewable energy export via circular liquid hydrogen carriers
Publisher: Elsevier BV
Date: 10-2023
Intrinsically Fluorescent Anti-Cancer Drugs
Publisher: MDPI AG
Date: 28-07-2022
Abstract: At present, about one-third of the total protein targets in the pharmaceutical research sector are kinase-based. While kinases have been attractive targets to combat many diseases, including cancer, selective kinase inhibition has been challenging, because of the high degree of structural homology in the active site where many kinase inhibitors bind. Despite efficacy as cancer drugs, kinase inhibitors can exhibit limited target specificity and rationalizing their target profiles in the context of precise molecular mechanisms or rearrangements is a major challenge for the field. Spectroscopic approaches such as infrared, Raman, NMR and fluorescence have the potential to provide significant insights into drug-target and drug-non-target interactions because of sensitivity to molecular environment. This review places a spotlight on the significance of fluorescence for extracting information related to structural properties, discovery of hidden conformers in solution and in target-bound state, binding properties (e.g., location of binding sites, hydrogen-bonding, hydrophobicity), kinetics as well as dynamics of kinase inhibitors. It is concluded that the information gleaned from an understanding of the intrinsic fluorescence from these classes of drugs may aid in the development of future drugs with improved side-effects and less disease resistance.
Conformational Plasticity in Tyrosine Kinase Inhibitor-Kinase Interactions Revealed with Fluorescence Spectroscopy and Theoretical Calculations
Publisher: American Chemical Society (ACS)
Date: 09-04-2018
Abstract: To understand drug-protein dynamics, it is necessary to account for drug molecular flexibility and binding site plasticity. Herein, we exploit fluorescence from a tyrosine kinase inhibitor, AG1478, as a reporter of its conformation and binding site environment when complexed with its cognate kinase. Water-soluble kinases, aminoglycoside phosphotransferase APH(3')-Ia and mitogen-activated protein kinase 14 (MAPK14), were chosen for this study. On the basis of our prior work, the AG1478 conformation (planar or twisted) was inferred from the fluorescence excitation spectrum and the polarity of the AG1478-binding site was deduced from the fluorescence emission spectrum, while red-edge excitation shift (REES) probed the heterogeneity of the binding site (protein conformation and hydration) distributions in the protein conformational ensemble. In the AG1478-APH(3')-Ia complex, both twisted (or partially twisted) and planar AG1478 conformations were evidenced from emission wavelength-dependent excitation spectra. The binding site environment provided by APH(3')-Ia was moderately polar (λ
A pH-induced conformational switch in a tyrosine kinase inhibitor identified by electronic spectroscopy and quantum chemical calculations
Publisher: Springer Science and Business Media LLC
Date: 24-11-2017
DOI: 10.1038/S41598-017-16583-Z
Abstract: Tyrosine kinase inhibitors (TKIs) are a major class of drug utilised in the clinic. During transit to their cognate kinases, TKIs will encounter different pH environments that could have a major influence on TKI structure. To address this, we report UV-Vis spectroscopic and computational studies of the TKI, AG1478, as a function of pH. The electronic absorption spectrum of AG1478 shifted by 10 nm (from 342 nm to 332 nm) from acid to neutral pH and split into two peaks (at 334 nm and 345 nm) in highly alkaline conditions. From these transitions, the pKa value was calculated as 5.58 ± 0.01. To compute structures and spectra, time-dependent density functional theory (TD-DFT) calculations were performed along with conductor-like polarizable continuum model (CPCM) to account for implicit solvent effect. On the basis of the theoretical spectra, we could assign the AG1478 experimental spectrum at acidic pH to a mixture of two twisted conformers (71% AG1478 protonated at quinazolyl nitrogen N(1) and 29% AG1478 protonated at quinazolyl nitrogen N(3)) and at neutral pH to the neutral planar conformer. The AG1478 absorption spectrum (pH 13.3) was fitted to a mixture of neutral (70%) and NH-deprotonated species (30%). These studies reveal a pH-induced conformational transition in a TKI.
Adsorption of Cytosine and AZA Derivatives of Cytidine on Au Single Crystal Surfaces
Publisher: American Chemical Society (ACS)
Date: 29-08-2013
DOI: 10.1021/JP404821T
Effects of alkyl side chains on properties of aliphatic amino acids probed using quantum chemical calculations
Publisher: International Union of Crystallography (IUCr)
Date: 29-07-2011
Micro-solvation of tyrosine-kinase inhibitor AG1478 explored with fluorescence spectroscopy and computational chemistry
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7RA04435F
Abstract: Fluorescence quenching of the anticancer AG1478, by at least three explicit water molecules, can be exploited to probe drug–protein binding interactions.
Correlation of electronic structures of three cyclic dipeptides with their photoemission spectra
Publisher: AIP Publishing
Date: 05-11-2010
DOI: 10.1063/1.3499740
Abstract: We have investigated the electronic structure of three cyclic dipeptides: cyclo(Glycyl-Glycyl) (cGG), cyclo(Leucyl-Prolyl) (cLP), and cyclo(Phenylalanyl-Prolyl) (cPP). These compounds are biologically active and cLP and cPP are derived from cGG (also known as diketopiperazine), by the addition of the respective functional groups of the amino acids, namely, phenyl, alkyl or a fused pyrrolidine ring (proline). Experimental valence and core level spectra have been interpreted in the light of theoretical calculations to identify the basic chemical properties associated with the central ring, and with the additional functional groups in cLP and cPP. The theoretically simulated spectra of all three cyclic dipeptides in both valence and core spaces agreed reasonably well with the experimental spectra. The three molecules displayed similarities in their core spectra, suggesting that the diketopiperazine structure plays an important role in determining the inner shell spectrum. The experimental C 1s spectra of cLP and cPP are analogous but differ from cGG due to the side chains attached to the diketopiperazine structure. Single spectral peaks in the N 1s (and O 1s) spectra of the dipeptides indicate that the chemical environment of the nitrogen atoms (and oxygen atoms) are very similar, although they show a small splitting in the simulated spectra of cPL and cPP, due to the reduction of their point group symmetry. Valence band spectra of the three dipeptides in the frontier orbital region of 9–11 eV exhibit similarities however theoretical analysis shows that significant changes occur due to the involvement of the side chain in the frontier orbitals of cPP, while lesser changes are found for cLP.
Exploring the electronic structure of 2,6-stelladione from momentum space I: the p-dominant molecular orbitals in the outer valence shell
Publisher: Elsevier BV
Date: 12-2003
Reinterpretation of Dynamic Vibrational Spectroscopy to Determine the Molecular Structure and Dynamics of Ferrocene
Publisher: Wiley
Date: 11-11-2016
Abstract: Molecular distortion of dynamic molecules gives a clear signature in the vibrational spectra, which can be modeled to give estimates of the energy barrier and the sensitivity of the frequencies of the vibrational modes to the reaction coordinate. The reaction coordinate method (RCM) utilizes ab initio-calculated spectra of the molecule in its ground and transition states together with their relative energies to predict the temperature dependence of the vibrational spectra. DFT-calculated spectra of the eclipsed (D
Orbital based electronic structural signatures of the guanine keto G-7H/G-9H tautomer pair as studied using dual space analysis
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.BPC.2005.12.006
Abstract: Electronic structural signatures of the guanine-7H and guanine-9H tautomers have been investigated on an orbital by orbital basis using dual space analysis. A combination of density functional theory (B3LYP/TZVP), the statistical average of model orbital potentials (SAOP/TZ2P) method and outer valence Green's function theory (OVGF/TZVP) has been used to generate optimal tautomer geometries and accurate ionization energy spectra for the guanine tautomer pair. The present work found that the non-planar form for both of the guanine keto pair possesses lower energies than their corresponding planar counterparts, and that the canonical form of the guanine-7H tautomer has slightly lower total energy than guanine-9H. This latter result is in agreement with previous experimental and theoretical findings. In the planar guanine pair the geometric parameters and anisotropic molecular properties are compared, focusing on changes caused by the mobile proton transfer. It is demonstrated that the mobile proton only causes limited disturbance to isotropic properties, such as geometry and the energetics, of the guanine keto tautomer pair. The exception to this general statement is for related local changes such as the N((7))-C((8)) and C((8))-N((9)) bond length resonance between the single and double bonds, reflecting the nitrogen atom being bonded with the mobile proton in the tautomers. The mobile proton distorts the electron distribution of the tautomers, which leads to significant changes in the molecular anisotropic properties. The dipole moment of guanine-7H is altered by about a factor of three, from 2.23 to 7.05 D (guanine-9H), and the molecular electrostatic potentials also reflect significant electron charge distortion. The outer valence orbital momentum distributions, which were obtained using the plane wave impulse approximation (PWIA), have demonstrated quantitatively that the outer valence orbitals of the tautomer pair can be ided into three groups. That is orbitals 1a''-7a'' and 18a', which do not have visible alternations in the tautomeric process (which consist of either pi orbitals or are close to the inner valence shell) a second group comprising orbitals 19a'-22a', 25a', 26a', 28a', 29a' and 31a', which show small perturbations as a result of the mobile hydrogen locations and group three, orbitals 23a', 24a', 27a', 30a' and 32a', which demonstrate significant changes due to the mobile proton transfer and are therefore considered as signature orbitals of the G-7H/G-9H keto tautomeric process.
Two conformers of a tyrosine kinase inhibitor (AG-1478) disclosed using simulated UV-Vis absorption spectroscopy
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6NJ01909A
Abstract: A quantum mechanical rationale for the observed UV-Vis spectrum of anti-cancer drug AG-1478 was accomplished using two conformers.
Molecular dynamics studies on the NMR structures of rabbit prion protein wild type and mutants: surface electrostatic charge distributions
Publisher: Informa UK Limited
Date: 08-08-2014
DOI: 10.1080/07391102.2014.947325
Abstract: Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer and elk, and humans. But for rabbits, studies have shown that they have a low susceptibility to be infected by prion diseases. This paper does molecular dynamics (MD) studies of rabbit NMR structures (of the wild type and its two mutants of two surface residues), in order to understand the specific mechanism of rabbit prion proteins (RaPrP(C)). Protein surface electrostatic charge distributions are specially focused to analyze the MD trajectories. This paper can conclude that surface electrostatic charge distributions indeed contribute to the structural stability of wild-type RaPrP(C) this may be useful for the medicinal treatment of prion diseases.
Blue shifted intramolecular C−H···O improper hydrogen bonds in conformers of zidovudine
Publisher: Elsevier BV
Date: 06-2010
Influence of functional groups on the Cα–Cβ chain of l-phenylalanine and its derivatives
Publisher: Elsevier BV
Date: 07-2010
Related Organisations
No related organisations have been discovered for Feng Wang.
Related Funding Activities
Discovery Projects - Grant ID: DP110101371
Start Date: 2011
End Date: 06-2017
Amount: $210,000.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP230100983
Start Date: 2023
End Date: 12-2025
Amount: $351,783.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP0450863
Start Date: 2004
End Date: 12-2007
Amount: $315,000.00
Funder: Australian Research Council
View Funded ActivityLinkage - International - Grant ID: LX0561315
Start Date: 12-2005
End Date: 12-2007
Amount: $16,000.00
Funder: Australian Research Council
View Funded Activity