Bruce Milne - Academia.edu (original) (raw)
Papers by Bruce Milne
Journal of The Chemical Society-perkin Transactions 1, May 22, 2002
J. Chem. Soc., Perkin Trans. 2, 2002, 1072-1075 DOI:10.1039/B201823N (Paper). Conformational chan... more J. Chem. Soc., Perkin Trans. 2, 2002, 1072-1075 DOI:10.1039/B201823N (Paper). Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 1. Cu 2+ and Zn 2+ induced conformational change. ...
Journal of the Chemical Society, Apr 24, 2002
ABSTRACT Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline ... more ABSTRACT Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.
Physical Chemistry Chemical Physics, 2023
Real-space self-interaction corrected (time-dependent) density functional theory has been used to... more Real-space self-interaction corrected (time-dependent) density functional theory has been used to investigate the ground-state electronic structure and optical absorption profiles of a series of linear oligomers inspired by the natural product telomestatin. Length-dependent development of plasmonic excitations in the UV region is seen in the neutral species which is augmented by polaron-type absorption with tunable wavelengths in the IR when the chains are doped with an additional electron/ hole. Combined with a lack of absorption in the visible region this suggests these oligomers as good candidates for applications such as transparent antennae in dye-sensitised solar energy collection materials. Due to strong longitudinal polarisation in their absorption spectra, these compounds are also indicated for use in nano-structured devices displaying orientation-sensitive optical responses.
arXiv (Cornell University), Feb 25, 2023
Real-space self-interaction corrected (time-dependent) density functional theory has been used to... more Real-space self-interaction corrected (time-dependent) density functional theory has been used to investigate the ground-state electronic structure and optical absorption profiles of a series of linear oligomers inspired by the natural product telomestatin. Length-dependent development of plasmonic excitations in the UV region is seen in the neutral species which is augmented by polaron-type absorption in the IR when the chains are doped with an additional electron/hole. Combined with a lack of absorption in the visible region this suggests these oligomers as good candidates for applications such as transparent antennae in dye-sensitised solar energy collection materials.
Proceedings of the National Academy of Sciences
A common challenge in drug design pertains to finding chemical modifications to a ligand that inc... more A common challenge in drug design pertains to finding chemical modifications to a ligand that increases its affinity to the target protein. An underutilized advance is the increase in structural biology throughput, which has progressed from an artisanal endeavor to a monthly throughput of hundreds of different ligands against a protein in modern synchrotrons. However, the missing piece is a framework that turns high-throughput crystallography data into predictive models for ligand design. Here, we designed a simple machine learning approach that predicts protein–ligand affinity from experimental structures of diverse ligands against a single protein paired with biochemical measurements. Our key insight is using physics-based energy descriptors to represent protein–ligand complexes and a learning-to-rank approach that infers the relevant differences between binding modes. We ran a high-throughput crystallography campaign against the SARS-CoV-2 main protease (M Pro ), obtaining parall...
Journal of physics, Sep 7, 2015
Synopsis Action spectroscopy provides key insights into the nature of electronic transitions of c... more Synopsis Action spectroscopy provides key insights into the nature of electronic transitions of coordination complexes such as porhyrin-containing biochromophores like chlorophyll or transition metal complexes such as tris(bipyridine)ruthenium.
Natural polymers, due to their inherent unique properties of biocompatibility and biodegradabilit... more Natural polymers, due to their inherent unique properties of biocompatibility and biodegradability, are highly appreciated as valuable ingredients of biomaterials and therefore are widely exploited in the biomedical field. Polysaccharides, incorporating various functionalities in their structures and exhibiting interesting physicochemical properties and significant biological activities, are considered attractive materials for the development of novel systems for bioapplications, such as drug delivery and tissue engineering. In this context, natural carbohydrates are increasingly utilized either in their native form or after chemical modification, so as to deliver tailor-made materials for specific applications. Marine algae produce polysaccharides that are regarded as safer and non-immunogenic, in contrast to those of animal origin. Ulvan, a sulphated polysaccharide located in the cell walls of green algae that possesses unique structural properties albeit its repeating unit shares chemical affinity with glycosoaminoglycans, such as hyaluronan and chondroitin sulphate, has been increasingly studied over the years for applications in the pharmaceutical field. The physicochemical properties and pharmacological activity of ulvan have been systematically investigated and a wide range of biological activities have been reported. Fibrous biocomposites comprising ulvan extracted from Ulva rigida and a number of copolymers were successfully prepared using the electrospinning technique. Moreover, novel hybrid scaffolds based on chemically cross-linked ulvan revealing highly porous interconnected structures were prepared, characterized and used as substrates for cell cultures. Our current results, in combination with the inherent cytocompatibility of ulvan, highlight the potential uses of the prepared ulvan-based biomaterials either as novel formulations for peptide/protein and/or drug delivery systems or as prospective scaffolds in tissue engineering.
![Research paper thumbnail of Sulfur-Containing Arsenical Mistaken for Dimethylarsinous Acid [DMA(III)] and Identified as a Natural Metabolite in Urine: Major Implications for Studies on Arsenic Metabolism and Toxicity](https://attachments.academia-assets.com/108493532/thumbnails/1.jpg)
](Chemical Research in Toxicology, Jul 17, 2004
Journal of Chemical Physics, Nov 1, 2019
A necessary first step in the development of technologies such as artificial photosynthesis is un... more A necessary first step in the development of technologies such as artificial photosynthesis is understanding the photoexcitation process within the basic building blocks of naturally-occurring light harvesting complexes (LHCs). The most important of these building blocks in biological LHCs such as LHC II from green plants are the chlorophyll a (Chl a) and chlorophyll b (Chl b) chromophores dispersed throughout the protein matrix. However, efforts to describe such systems are still hampered by the lack of computationally efficient and accurate methods that are able to describe optical absorption in large biomolecules. In this work we employ a highly efficient linear combination of atomic orbitals (LCAOs) to represent the Kohn-Sham (KS) wave functions at the density functional theory (DFT) level and perform time dependent density functional theory (TDDFT) in either the reciprocal space and frequency domain (LCAO-TDDFT-k-ω) or real space and time domain (LCAO-TDDFT-r-t) calculations of the optical absorption spectra of Chl a and b monomers and dimers. We find our LCAO-TDDFT-k-ω and LCAO-TDDFT-r-t calculations reproduce results obtained with a plane wave (PW) representation of the KS wave functions (PW-TDDFT-k-ω), but with a significant reduction in computational effort. Moreover, by applying the GLLB-SC derivative discontinuity correction ∆ x to the KS eigenenergies, with both LCAO-TDDFT-k-ω and LCAO-TDDFT-r-t methods we are able to semi-quantitatively reproduce the experimentally measured photoinduced dissociation (PID) results. This work opens the path to first principles calculations of optical excitations in macromolecular systems.
International Journal of Molecular Sciences, Jan 16, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Physical Chemistry A, Jan 29, 2015
The first-order hyperpolarizability, β, has been calculated for a group of marine natural product... more The first-order hyperpolarizability, β, has been calculated for a group of marine natural products, the makaluvamines. These compounds possess a common cationic pyrroloiminoquinone structure that is substituted to varying degrees. Calculations at the MP2 level indicate that makaluvamines possessing phenolic side chains conjugated with the pyrroloiminoquinone moiety display large β values, while breaking this conjugation leads to a dramatic decrease in the calculated hyperpolarizability. This is consistent with a charge-transfer donor-π-acceptor (D−π−A) structure type, characteristic of nonlinear optical chromophores. Dynamic hyperpolarizabilities calculated using resonance-convergent timedependent density functional theory coupled to polarizable continuum model (PCM) solvation suggest that significant resonance enhancement effects can be expected for incident radiation with wavelengths around 800 nm. The results of the current work suggest that the pyrroloiminoquinone moiety represents a potentially useful new chromophore subunit, in particular for the development of molecular probes for biological imaging. The introduction of solvent−solute interactions in the theory is conventionally made in a density matrix formalism, and the present work will provide detailed account of the approximations that need to be introduced in wave function theory and our program implementation. The program implementation as such is achieved by a mere combination of existing modules from previous developments, and it is here only briefly reviewed.
Tetrahedron, May 1, 2017
Users may download and print one copy of any publication from the public portal for the purpose... more Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Analytical and Bioanalytical Chemistry, Feb 24, 2008
Mercury in plants or animal tissue is supposed to occur in the form of complexes formed with biol... more Mercury in plants or animal tissue is supposed to occur in the form of complexes formed with biologically relevant thiols (biothiols), rather than as free cation. We describe a technique for the separation and molecular identification of mercury and methylmercury complexes derived from their reactions with cysteine (Cys) and glutathione (GS): Hg(Cys) 2 , Hg(GS) 2 , MeHgCys, MeHgGS. Complexes were characterised by electrospray mass spectrometry (MS) equipped with an ion trap and the fragmentation pattern of MeHgCys was explained by using MP2 and B3LYP calculations, showing the importance of mercuryamine interactions in the gas phase. Chromatographic baseline separation was performed within 10 min with formic acid as the mobile phase on a reversed-phase column. Detection was done by online simultaneous coupling of ES-MS and inductively coupled plasma MS. When the mercury complexes were spiked in real samples (plant extracts), no perturbation of the separation and detection conditions was observed, suggesting that this method is capable of detecting mercury biothiol complexes in plants.
Angewandte Chemie, Oct 6, 2008
Journal of Physical Chemistry A, Jun 11, 2018
First-principles calculations have been used to investigate the potential use of circular dichroi... more First-principles calculations have been used to investigate the potential use of circular dichroism (CD) spectroscopy in single molecule sensing. Using a real-space implementation of time-dependent density functional theory (TDDFT), several systems involving single-walled carbon nanotubes (SWCNT) and small molecules have been studied to evaluate their CD response. Large induced CD (ICD) effects, differing for each test molecule, were observed in all SWCNT-molecule complexes. As the SWCNT used in this study shows no intrinsic CD response, the ICD spectra are the result of interaction with the small molecules. This finding is general and independent of the (a)chiral nature of the adsorbed molecule. Our results indicate that it is possible to design a system that uses SWCNT for detection of molecules using the change in CD spectrum of the system induced by adsorption of the molecule onto the SWCNT surface.
Journal of Natural Products, Feb 8, 2019
Analytical and Bioanalytical Chemistry, Jan 13, 2007
The major arsenosugar compounds have been reported to be hydride-generation-active, however to a ... more The major arsenosugar compounds have been reported to be hydride-generation-active, however to a lesser extent in comparison with the inorganic arsenicals. We report here for the first time the identity and quantity of the volatile arsenicals generated by As-sugar-SO 3 , As-sugar-SO 4 , dimethylarsinoyl acetic acid and dimethylarsinoyl ethanol. Only one major volatile compound was identified for all four compounds studied: dimethylarsine. This means that the As-C bond to the longer carbon chain was cleaved during the hydride-generation process. Theoretical calculations at the RHF/6-31G(d,p) ab initio level confirm that this As-C bond is much weaker than the As-CH 3 bonds. Furthermore, it was revealed that the sulphur analogue of dimethylarsinic acid (DMAS) is hydride-generation-active at pH 7 in contrast to dimethylarsinic acid, despite the fact that arsenic is also pentavalent. This has been substantiated by the calculation of the change in susceptibility of the arsenic towards nucleophilic attack when oxygen is replaced by sulphur. Hence, DMAS can easily be mistaken for a trivalent arsenic species.
Physical Chemistry Chemical Physics, 2015
We have performed gas-phase absorption spectroscopy in the Soret-band region of chlorophyll (Chl)... more We have performed gas-phase absorption spectroscopy in the Soret-band region of chlorophyll (Chl) a and b tagged by quaternary ammonium ions together with time-dependent density functional theory (TD-DFT) calculations. This band is the strongest in the visible region of metalloporphyrins and an important reporter on the microenvironment. The cationic charge tags were tetramethylammonium, tetrabutylammonium, and acetylcholine, and the dominant dissociation channel in all cases was breakage of the complex to give neutral Chl and the charge tag as determined by photoinduced dissociation mass spectroscopy. Two photons were required to induce fragmentation on the time scale of the experiment (microseconds). Action spectra were recorded where the yield of the tag as a function of excitation wavelength was sampled. These spectra are taken to represent the corresponding absorption spectra. In the case of Chl a we find that the tag hardly influences the band maximum which for all three tags is at 403 AE 5 nm. A smaller band with maximum at 365 AE 10 nm was also measured for all three complexes. The spectral quality is worse in the case of Chl b due to lower ion beam currents; however, there is clear evidence for the absorption being to the red of that of Chl a (most intense peak at 409 AE 5 nm) and also a more split band. Our results demonstrate that the change in the Soret-band spectrum when one peripheral substituent (CH 3) is replaced by another (CHO) is an intrinsic effect. First principles TD-DFT calculations agree with our experiments, supporting the intrinsic nature of the difference between Chl a and b and also displaying minimal spectral changes when different charge tags are employed. The deviations between theory and experiment have allowed us to estimate that the Soret-band absorption maxima in vacuo for the neutral Chl a and Chl b should occur at 405 nm and 413 nm, respectively. Importantly, the Soret bands of the isolated species are significantly blueshifted compared to those of solvated Chl and Chl-proteins. The protein microenvironment is certainly not innocent of perturbing the electronic structure of Chls.
International Journal of Mass Spectrometry, May 1, 2014
Highlights Fragment ion masses of photoexcited oxyluciferin anions were identified. Isotope-l... more Highlights Fragment ion masses of photoexcited oxyluciferin anions were identified. Isotope-labelling reveals that the thiazolyl is most susceptible to fragmentation. Dominant fragment ion is deprotonated 2-cyano-6-hydroxybenzothiazole. In the firefly the dominant fragment ion, if formed, is recycled to D-luciferin.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally compl... more Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex naturally occurring metabolites across all three domains of life. Despite the structural diversity of RiPPs that stems from the extensive post-translational modifications, only α-amino acid residues have been found in known RiPPs. Here we report discovery of a new 27-mer peptide, kintamdin, using comprehensive MS and NMR structural elucidation and genomic analysis together with computational modelling. The peptide features a β-amino acid residue and a new thioether macrocyclic ring. Heterologous expression and gene inactivation allowed the identification of the minimal biosynthetic gene cluster (BGC). The gene products in kin BGC share low homologues compared to other known RiPP pathways, further rendering the novelty of kintamdin. Biochemical analysis indicated that KinO mediate di-methylation reaction to yield kintamidn. Finally, the occurrence of the kin-like BGCs in Gram-positive ...
Journal of The Chemical Society-perkin Transactions 1, May 22, 2002
J. Chem. Soc., Perkin Trans. 2, 2002, 1072-1075 DOI:10.1039/B201823N (Paper). Conformational chan... more J. Chem. Soc., Perkin Trans. 2, 2002, 1072-1075 DOI:10.1039/B201823N (Paper). Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 1. Cu 2+ and Zn 2+ induced conformational change. ...
Journal of the Chemical Society, Apr 24, 2002
ABSTRACT Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline ... more ABSTRACT Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.
Physical Chemistry Chemical Physics, 2023
Real-space self-interaction corrected (time-dependent) density functional theory has been used to... more Real-space self-interaction corrected (time-dependent) density functional theory has been used to investigate the ground-state electronic structure and optical absorption profiles of a series of linear oligomers inspired by the natural product telomestatin. Length-dependent development of plasmonic excitations in the UV region is seen in the neutral species which is augmented by polaron-type absorption with tunable wavelengths in the IR when the chains are doped with an additional electron/ hole. Combined with a lack of absorption in the visible region this suggests these oligomers as good candidates for applications such as transparent antennae in dye-sensitised solar energy collection materials. Due to strong longitudinal polarisation in their absorption spectra, these compounds are also indicated for use in nano-structured devices displaying orientation-sensitive optical responses.
arXiv (Cornell University), Feb 25, 2023
Real-space self-interaction corrected (time-dependent) density functional theory has been used to... more Real-space self-interaction corrected (time-dependent) density functional theory has been used to investigate the ground-state electronic structure and optical absorption profiles of a series of linear oligomers inspired by the natural product telomestatin. Length-dependent development of plasmonic excitations in the UV region is seen in the neutral species which is augmented by polaron-type absorption in the IR when the chains are doped with an additional electron/hole. Combined with a lack of absorption in the visible region this suggests these oligomers as good candidates for applications such as transparent antennae in dye-sensitised solar energy collection materials.
Proceedings of the National Academy of Sciences
A common challenge in drug design pertains to finding chemical modifications to a ligand that inc... more A common challenge in drug design pertains to finding chemical modifications to a ligand that increases its affinity to the target protein. An underutilized advance is the increase in structural biology throughput, which has progressed from an artisanal endeavor to a monthly throughput of hundreds of different ligands against a protein in modern synchrotrons. However, the missing piece is a framework that turns high-throughput crystallography data into predictive models for ligand design. Here, we designed a simple machine learning approach that predicts protein–ligand affinity from experimental structures of diverse ligands against a single protein paired with biochemical measurements. Our key insight is using physics-based energy descriptors to represent protein–ligand complexes and a learning-to-rank approach that infers the relevant differences between binding modes. We ran a high-throughput crystallography campaign against the SARS-CoV-2 main protease (M Pro ), obtaining parall...
Journal of physics, Sep 7, 2015
Synopsis Action spectroscopy provides key insights into the nature of electronic transitions of c... more Synopsis Action spectroscopy provides key insights into the nature of electronic transitions of coordination complexes such as porhyrin-containing biochromophores like chlorophyll or transition metal complexes such as tris(bipyridine)ruthenium.
Natural polymers, due to their inherent unique properties of biocompatibility and biodegradabilit... more Natural polymers, due to their inherent unique properties of biocompatibility and biodegradability, are highly appreciated as valuable ingredients of biomaterials and therefore are widely exploited in the biomedical field. Polysaccharides, incorporating various functionalities in their structures and exhibiting interesting physicochemical properties and significant biological activities, are considered attractive materials for the development of novel systems for bioapplications, such as drug delivery and tissue engineering. In this context, natural carbohydrates are increasingly utilized either in their native form or after chemical modification, so as to deliver tailor-made materials for specific applications. Marine algae produce polysaccharides that are regarded as safer and non-immunogenic, in contrast to those of animal origin. Ulvan, a sulphated polysaccharide located in the cell walls of green algae that possesses unique structural properties albeit its repeating unit shares chemical affinity with glycosoaminoglycans, such as hyaluronan and chondroitin sulphate, has been increasingly studied over the years for applications in the pharmaceutical field. The physicochemical properties and pharmacological activity of ulvan have been systematically investigated and a wide range of biological activities have been reported. Fibrous biocomposites comprising ulvan extracted from Ulva rigida and a number of copolymers were successfully prepared using the electrospinning technique. Moreover, novel hybrid scaffolds based on chemically cross-linked ulvan revealing highly porous interconnected structures were prepared, characterized and used as substrates for cell cultures. Our current results, in combination with the inherent cytocompatibility of ulvan, highlight the potential uses of the prepared ulvan-based biomaterials either as novel formulations for peptide/protein and/or drug delivery systems or as prospective scaffolds in tissue engineering.
Chemical Research in Toxicology, Jul 17, 2004
Journal of Chemical Physics, Nov 1, 2019
A necessary first step in the development of technologies such as artificial photosynthesis is un... more A necessary first step in the development of technologies such as artificial photosynthesis is understanding the photoexcitation process within the basic building blocks of naturally-occurring light harvesting complexes (LHCs). The most important of these building blocks in biological LHCs such as LHC II from green plants are the chlorophyll a (Chl a) and chlorophyll b (Chl b) chromophores dispersed throughout the protein matrix. However, efforts to describe such systems are still hampered by the lack of computationally efficient and accurate methods that are able to describe optical absorption in large biomolecules. In this work we employ a highly efficient linear combination of atomic orbitals (LCAOs) to represent the Kohn-Sham (KS) wave functions at the density functional theory (DFT) level and perform time dependent density functional theory (TDDFT) in either the reciprocal space and frequency domain (LCAO-TDDFT-k-ω) or real space and time domain (LCAO-TDDFT-r-t) calculations of the optical absorption spectra of Chl a and b monomers and dimers. We find our LCAO-TDDFT-k-ω and LCAO-TDDFT-r-t calculations reproduce results obtained with a plane wave (PW) representation of the KS wave functions (PW-TDDFT-k-ω), but with a significant reduction in computational effort. Moreover, by applying the GLLB-SC derivative discontinuity correction ∆ x to the KS eigenenergies, with both LCAO-TDDFT-k-ω and LCAO-TDDFT-r-t methods we are able to semi-quantitatively reproduce the experimentally measured photoinduced dissociation (PID) results. This work opens the path to first principles calculations of optical excitations in macromolecular systems.
International Journal of Molecular Sciences, Jan 16, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Physical Chemistry A, Jan 29, 2015
The first-order hyperpolarizability, β, has been calculated for a group of marine natural product... more The first-order hyperpolarizability, β, has been calculated for a group of marine natural products, the makaluvamines. These compounds possess a common cationic pyrroloiminoquinone structure that is substituted to varying degrees. Calculations at the MP2 level indicate that makaluvamines possessing phenolic side chains conjugated with the pyrroloiminoquinone moiety display large β values, while breaking this conjugation leads to a dramatic decrease in the calculated hyperpolarizability. This is consistent with a charge-transfer donor-π-acceptor (D−π−A) structure type, characteristic of nonlinear optical chromophores. Dynamic hyperpolarizabilities calculated using resonance-convergent timedependent density functional theory coupled to polarizable continuum model (PCM) solvation suggest that significant resonance enhancement effects can be expected for incident radiation with wavelengths around 800 nm. The results of the current work suggest that the pyrroloiminoquinone moiety represents a potentially useful new chromophore subunit, in particular for the development of molecular probes for biological imaging. The introduction of solvent−solute interactions in the theory is conventionally made in a density matrix formalism, and the present work will provide detailed account of the approximations that need to be introduced in wave function theory and our program implementation. The program implementation as such is achieved by a mere combination of existing modules from previous developments, and it is here only briefly reviewed.
Tetrahedron, May 1, 2017
Users may download and print one copy of any publication from the public portal for the purpose... more Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Analytical and Bioanalytical Chemistry, Feb 24, 2008
Mercury in plants or animal tissue is supposed to occur in the form of complexes formed with biol... more Mercury in plants or animal tissue is supposed to occur in the form of complexes formed with biologically relevant thiols (biothiols), rather than as free cation. We describe a technique for the separation and molecular identification of mercury and methylmercury complexes derived from their reactions with cysteine (Cys) and glutathione (GS): Hg(Cys) 2 , Hg(GS) 2 , MeHgCys, MeHgGS. Complexes were characterised by electrospray mass spectrometry (MS) equipped with an ion trap and the fragmentation pattern of MeHgCys was explained by using MP2 and B3LYP calculations, showing the importance of mercuryamine interactions in the gas phase. Chromatographic baseline separation was performed within 10 min with formic acid as the mobile phase on a reversed-phase column. Detection was done by online simultaneous coupling of ES-MS and inductively coupled plasma MS. When the mercury complexes were spiked in real samples (plant extracts), no perturbation of the separation and detection conditions was observed, suggesting that this method is capable of detecting mercury biothiol complexes in plants.
Angewandte Chemie, Oct 6, 2008
Journal of Physical Chemistry A, Jun 11, 2018
First-principles calculations have been used to investigate the potential use of circular dichroi... more First-principles calculations have been used to investigate the potential use of circular dichroism (CD) spectroscopy in single molecule sensing. Using a real-space implementation of time-dependent density functional theory (TDDFT), several systems involving single-walled carbon nanotubes (SWCNT) and small molecules have been studied to evaluate their CD response. Large induced CD (ICD) effects, differing for each test molecule, were observed in all SWCNT-molecule complexes. As the SWCNT used in this study shows no intrinsic CD response, the ICD spectra are the result of interaction with the small molecules. This finding is general and independent of the (a)chiral nature of the adsorbed molecule. Our results indicate that it is possible to design a system that uses SWCNT for detection of molecules using the change in CD spectrum of the system induced by adsorption of the molecule onto the SWCNT surface.
Journal of Natural Products, Feb 8, 2019
Analytical and Bioanalytical Chemistry, Jan 13, 2007
The major arsenosugar compounds have been reported to be hydride-generation-active, however to a ... more The major arsenosugar compounds have been reported to be hydride-generation-active, however to a lesser extent in comparison with the inorganic arsenicals. We report here for the first time the identity and quantity of the volatile arsenicals generated by As-sugar-SO 3 , As-sugar-SO 4 , dimethylarsinoyl acetic acid and dimethylarsinoyl ethanol. Only one major volatile compound was identified for all four compounds studied: dimethylarsine. This means that the As-C bond to the longer carbon chain was cleaved during the hydride-generation process. Theoretical calculations at the RHF/6-31G(d,p) ab initio level confirm that this As-C bond is much weaker than the As-CH 3 bonds. Furthermore, it was revealed that the sulphur analogue of dimethylarsinic acid (DMAS) is hydride-generation-active at pH 7 in contrast to dimethylarsinic acid, despite the fact that arsenic is also pentavalent. This has been substantiated by the calculation of the change in susceptibility of the arsenic towards nucleophilic attack when oxygen is replaced by sulphur. Hence, DMAS can easily be mistaken for a trivalent arsenic species.
Physical Chemistry Chemical Physics, 2015
We have performed gas-phase absorption spectroscopy in the Soret-band region of chlorophyll (Chl)... more We have performed gas-phase absorption spectroscopy in the Soret-band region of chlorophyll (Chl) a and b tagged by quaternary ammonium ions together with time-dependent density functional theory (TD-DFT) calculations. This band is the strongest in the visible region of metalloporphyrins and an important reporter on the microenvironment. The cationic charge tags were tetramethylammonium, tetrabutylammonium, and acetylcholine, and the dominant dissociation channel in all cases was breakage of the complex to give neutral Chl and the charge tag as determined by photoinduced dissociation mass spectroscopy. Two photons were required to induce fragmentation on the time scale of the experiment (microseconds). Action spectra were recorded where the yield of the tag as a function of excitation wavelength was sampled. These spectra are taken to represent the corresponding absorption spectra. In the case of Chl a we find that the tag hardly influences the band maximum which for all three tags is at 403 AE 5 nm. A smaller band with maximum at 365 AE 10 nm was also measured for all three complexes. The spectral quality is worse in the case of Chl b due to lower ion beam currents; however, there is clear evidence for the absorption being to the red of that of Chl a (most intense peak at 409 AE 5 nm) and also a more split band. Our results demonstrate that the change in the Soret-band spectrum when one peripheral substituent (CH 3) is replaced by another (CHO) is an intrinsic effect. First principles TD-DFT calculations agree with our experiments, supporting the intrinsic nature of the difference between Chl a and b and also displaying minimal spectral changes when different charge tags are employed. The deviations between theory and experiment have allowed us to estimate that the Soret-band absorption maxima in vacuo for the neutral Chl a and Chl b should occur at 405 nm and 413 nm, respectively. Importantly, the Soret bands of the isolated species are significantly blueshifted compared to those of solvated Chl and Chl-proteins. The protein microenvironment is certainly not innocent of perturbing the electronic structure of Chls.
International Journal of Mass Spectrometry, May 1, 2014
Highlights Fragment ion masses of photoexcited oxyluciferin anions were identified. Isotope-l... more Highlights Fragment ion masses of photoexcited oxyluciferin anions were identified. Isotope-labelling reveals that the thiazolyl is most susceptible to fragmentation. Dominant fragment ion is deprotonated 2-cyano-6-hydroxybenzothiazole. In the firefly the dominant fragment ion, if formed, is recycled to D-luciferin.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally compl... more Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex naturally occurring metabolites across all three domains of life. Despite the structural diversity of RiPPs that stems from the extensive post-translational modifications, only α-amino acid residues have been found in known RiPPs. Here we report discovery of a new 27-mer peptide, kintamdin, using comprehensive MS and NMR structural elucidation and genomic analysis together with computational modelling. The peptide features a β-amino acid residue and a new thioether macrocyclic ring. Heterologous expression and gene inactivation allowed the identification of the minimal biosynthetic gene cluster (BGC). The gene products in kin BGC share low homologues compared to other known RiPP pathways, further rendering the novelty of kintamdin. Biochemical analysis indicated that KinO mediate di-methylation reaction to yield kintamidn. Finally, the occurrence of the kin-like BGCs in Gram-positive ...