Single Sulfur Atom Research Articles

Sulfur-tetrazine as highly efficient visible-light activatable photo-trigger for designing photoactivatable fluorescence biomolecules.

Light-activated fluorescence represents a potent tool for investigating subcellular structures and dynamics, offering enhanced control over the temporal and spatial aspects of the fluorescence signal. While alkyl-substituted tetrazine has previously been reported as a photo-trigger for various fluorophore scaffolds, its limited photochemical efficiency and high activation energy have constrained its widespread application at the biomolecular level. In this study, we demonstrate that a single sulfur atom substitution of tetrazine greatly enhances the photochemical properties of tetrazine conjugates and significantly improves their photocleavage efficiency. Notably, the resulting sulfur-tetrazine can be activated using a lower-energy light source, thus transforming it into a valuable visible-light photo-trigger. To introduce this photo-trigger into biological systems, we have developed a series of visible-light activatable small molecular dyes, along with a photoactivatable noncanonical amino acid containing sulfur-tetrazine. Using the Genetic Code Expansion technology, this novel amino acid is genetically incorporated into fluorescent protein molecules, serving as a phototrigger to create an innovative photoactivatable protein. These advancements in tetrazine-scaffold photo-trigger design open up new avenues for generating photoactivatable biomolecules, promising to greatly facilitate the exploration of biological functions and structures.

Ag–S Type Quantum Dots versus Superatom Nanocatalyst: A Single Sulfur Atom Modulated Decarboxylative Radical Cascade Reaction

The preparation of high-nuclearity silver nanoclusters in quantitative yield remains exclusive and their potential applications in the catalysis of organic reactions are still undeveloped. Here, we have synthesized a quantum dot (QD)-based catalyst, [Ag62S13(SBut)32](PF6)4 (denoted as Ag62S12-S) in excellent yield that enables the direct synthesis of pharmaceutically precious 3,4-dihydroquinolinone in 92% via a decarboxylative radical cascade reaction of cinnamamide with α-oxocarboxylic acid under mild reaction conditions. In comparison, a superatom [Ag62S12(SBut)32](PF6)2 (denoted as Ag62S12) with identical surface anatomy and size, but without a central S2- atom in the core, gives an improved yield (95%) in a short time and exhibits higher reactivity. Multiple characterization techniques (single-crystal X-ray diffraction, nuclear magnetic resonance (1H and 31P), electrospray ionization mass spectrometry, energy dispersive X-ray spectroscopy, Brunauer-Emmett-Teller (BET), Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis) confirm the formation of Ag62S12-S. The BET results expose the total active surface area in supporting a single e- transfer reaction mechanism. Density functional theory reveals that leaving the central S atom of Ag62S12-S leads to higher charge transfer from Ag62S12 to the reactant, accelerates the decarboxylation process, and correlates the catalytic properties with the structure of the nanocatalyst.

Dual occupations of sulfur induced band flattening and chemical bond softening in p-type SyCo4Sb12-2yS2y skutterudites

The electronegative filling in skutterudites not only broadened the scope of filling atoms, but also facilitated the preparation of p-type skutterudites. However, the introduction of a single sulfur atom in the Co4Sb12 cannot be achieved without charge compensation through the traditional equilibrium method. In the present study, the dual occupations of S-atoms by self-charge compensation were shown as the most stable forms under high pressure, and a series of p-type SyCo4Sb12−2yS2y skutterudites was successfully prepared by high-pressure-high-temperature (HPHT) method. The electronic structures and transport properties of as-obtained materials were investigated, and the related mechanisms were explored. The results suggested that the presence of S-impurities led to flattening of the electronic band that led to a higher Seebeck coefficient. The S-doped Co4Sb12 displayed lower elastic modulus, elastic constant, and Debye temperature, thus indicating the chemical bond softening in skutterudites. The thermal conductivities of SyCo4Sb12−2yS2y compounds reduced monotonously with the increase in S-content. This study provides a new and promising avenue for optimizing the thermoelectric properties of p-type Co4Sb12.

Chemical transformation and dissociation of amino acids on metal sulfide surface: Insights from DFT into the effect of surface vacancies on alanine-sphalerite system

The affinity of amino acid species toward mineral surfaces is a favorable phenomenon in green material science applications. To this end, we performed a DFT calculation to study adsorption of alanine on the sphalerite (ZnS) surface, focusing on the role of surface vacancy defects by removing single sulfur, single zinc and double neighboring congruent atoms from the outermost layer. Removal of single sulfur or zinc atom led to surface reconstruction by forming favorable local Zn-Zn and S-S bonds around the defect sites, respectively. The presence of double neighboring congruent vacancies and their relative positions altered the adsorption configuration to more complicated modes. The lowest-energy configuration was predicted when both sulfur and zinc atoms were removed from the upper hill of the surface. In this case, alanine was dissociatively adsorbed on the surface, and a tridentate bond was formed between alanine and two zinc atoms on the surface. The alanine affinity was also significantly more stable than the defect-free surface with an energy difference of about 55 kcal/mol. In another special case with two Zn and S vacancies, respectively, on the downward and upper hills, alanine underwent a chemical transformation from neutral to zwitterionic form according to an intramolecular dissociation reaction.

Site-Selective Dissociation upon Sulfur L-Edge X-ray Absorption in a Gas-Phase Protonated Peptide.

Site-selective dissociation induced by core photoexcitation of biomolecules is of key importance for the understanding of radiation damage processes and dynamics and for its promising use as "chemical scissors" in various applications. However, identifying products of site-selective dissociation in large molecules is challenging at the carbon, nitrogen, and oxygen edges because of the high recurrence of these atoms and related chemical groups. In this paper, we present the observation of site-selective dissociation at the sulfur L-edge in the gas-phase peptide methionine enkephalin, which contains only a single sulfur atom. Near-edge X-ray absorption mass spectrometry has revealed that the resonant S 2p → σ*C-S excitation of the sulfur contained in the methionine side chain leads to site-selective dissociation, which is not the case after core ionization above the sulfur L-edge. The prospects of such results for the study of charge dynamics in biomolecular systems are discussed.

The Effect of Sulfur Atom Substitution on Organophosphorus Inhibitors of Butyrylcholinesterase

Butyrylcholinesterase (BuChE) is an enzyme that is highly upregulated in the pathogenesis of Alzheimer's Disease (AD) and contributes to the symptomatic cognitive decline through the hydrolysis of the neurotransmitter, acetylcholine. We have recently developed BuChE-specific, reversible organophosphorus inhibitors in which two phosphates are linked by an alkyl chain. Subsequent changes in drug design led to a better and smaller inhibition constant (Ki) by replacing the two oxygen atoms in the linker with sulfur atoms. Therefore, it is hypothesized that the position as well as an increase in the number of sulfur substitutions around the phosphorus atom will lead to a more potent inhibitor design. To evaluate the effects of these sulfur atoms on inhibition, dibutyl hexyl phosphate will be used as a scaffold for making a library of potential compounds, each with different number and location of substitutions. The reversibility of inhibition and the specificity is determined through an in vitro competition assay by incubating BuChE with inhibitor for various time intervals and then doping in butyrylthiocholine, a molecule that can be hydrolyzed by BuChE; the hydrolyzed product will react with Ellman's reagent to give an absorbance reading at 412 nanometers. Preliminary data for a single sulfur atom substitution on the hexyl chain shows about a 50-fold decrease in Ki compared to the control that has all oxygen atoms (1.3 versus 50 μM, respectively). When assayed against acetylcholinesterase, no inhibition was observed. Analogs bearing a thiophosphoryl group (P=S) show decreased inhibition compared to the phosphoryl (P=O) compounds (1.3 versus 3.4 μM). Despite the difference in location, a single substitution has led to an irreversible, yet selective inhibition of BuChE. The insight from this study will give guidance towards the rational design of better inhibitors of BuChE that can potentially decelerate the symptomatic progression of AD. Support or Funding Information This project is supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R25GM071638. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health. Library of phosphate and phosphorothioate compounds that will be evaluated for selective inhibition of butyrylcholinesterase This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Palladium(II) Polynuclear Complex with β-Mercaptoethanol

A hexanuclear palladium complex with β-mercaptoethanol was synthesized and characterized by various physical methods. A single sulfur atom participates in the coordination and binds two palladium atoms. The hydroxyl group of the ligand is not involved in the complex formation. A crown-shaped hexanuclear cycle without a metal-metal bond is formed.

Surface Single-Atom Tailoring of a Gold Nanoparticle.

Surface single-atom tailoring of a gold nanoparticle, that is, adding, removing, or replacing one surface atom on a structure-resolved nanoparticle in a controlled manner, is very exciting yet challenging and has not been hitherto achieved. Herein we report the first realization of the introduction of a single sulfur atom onto the surface of the structure-unraveled Au60S6(SCH2Ph)36 nanoparticle. Single-crystal X-ray crystallography reveals that the as-obtained nanoparticle consists of one Au17 kernel protected by one Au20S3(SCH2Ph)18 and one unprecedented Au23S4(SCH2Ph)18 motif with the introduced sulfur atom included as a tetrahedral-coordinated μ4-S. The introduced sulfur leads to the changes of both internal structure and crystallographic arrangement. Unlike the case of 6HLH arrangement in Au60S6(SCH2Ph)36 crystals, the "ABAB" arrangement in Au60S7(SCH2Ph)36 crystals enhances the solid photoluminescence of amorphous Au60S7(SCH2Ph)36 and brings a slight redshift of the maximum emission. The extensive near-infrared emission provides Au60S7(SCH2Ph)36 potential applications in some fields such as anticounterfeiting, imaging, etc.

Hemilability of the 1,2-Bis(dimethylphosphino)ethane (dmpe) Ligand in Cp*Mo(NO)(κ2-dmpe).

Reaction of Cp*Mo(NO)Cl2 with 1 equiv of 1,2-bis(dimethylphosphino)ethane (dmpe) in THF at ambient temperature forms [Cp*Mo(NO)(Cl)(κ2-dmpe)]Cl (1), which is isolable as an analytically pure yellow powder in 65% yield. Further addition of 2 equiv of Cp2Co to 1 in CH2Cl2 affords dark red Cp*Mo(NO)(κ2-dmpe) (2), which was isolated in 36% yield by recrystallization from Et2O at -30 °C. Reaction of a benzene solution of 2 with an equimolar amount of elemental sulfur results in the immediate production of dark blue (μ-S)[Cp*Mo(NO)(κ1-dmpeS)]2 (3), which is a rare example of a bimetallic transition-metal complex bridged by only a single sulfur atom and involving Mo═S═Mo bonding. In contrast, reaction of 2 with an excess of sulfur in benzene results in the formation of Cp*Mo(NO)(η2-S2)(κ1-dmpeS) (4). Complex 4 can also be formed by the addition of elemental sulfur to 3, thereby indicating that 3 is a precursor to 4. Cp*Mo(NO)(κ2-dmpe) (2) also undergoes interesting transformations when treated with organic bromides. For instance, reaction of 2 with 5 equiv benzyl bromide in THF produces the bimetallic complex (μ-dmpe)[Cp*Mo(NO)Br2]2 (5) and bibenzyl after 4 d at 70 °C probably via radical intermediates. In contrast to its reaction with benzyl bromide, complex 2 forms [Mo(NO)Br2(κ2-dmpe)]2 (6), olefin, alkane, and Cp*H when treated with 5 equiv of 1-bromopropane or 1-bromooctane in THF at 70 °C for 72 h. Interestingly, complex 2 does not display any reactivity with bromobenzene or 1-bromoadamantane even after being heated for several days at 70 °C. All new complexes were characterized by conventional spectroscopic and analytical methods, and the solid-state molecular structures of most of them were established by single-crystal X-ray crystallographic analyses.

Pendant structure governed the selectivity of Pd2+ using disubstituted polyacetylenes with sulfur functions and the application of thiophanate-methyl detection

A series of disubstituted polyacetylenes-based fluorescent chemosensors for Pd2+ has been designed and synthesized. The optimization of sensing performance for Pd2+ ions is realized through modulating the coordination mode, type and number of coordination atoms in pendant groups. The receptor groups containing both N and S atoms (Poly [1-phenyl-2-[3-(2-pyridylmercapto)propyl]acetylene] (P2) and Poly [1-phenyl-2-[3-(5-methyl-1,3,4-thiadiazole-2-mercapto)propyl]acetylene] (P4)) can respond simultaneously for Pd2+ and Pt4+/2+ ions, and the only introduction of sulfur as the ligand atoms (Poly [1-phenyl-2-[3-(p-methylphenylthio)propyl]acetylene] (P1) and Poly [1-phenyl-2-[3-(2-Thienylthio)propyl]acetylene] (P3)) can exhibit high selectivity for Pd2+. P3 containing double sulfur atoms in pendants exhibits more high selectivity and sensitivity toward Pd2+ than that of P1 containing single sulfur atom. Aforementioned results were illustrated by fluorescence titration, Ksv fitting and cyclic voltammetry (CV) analysis. The emission of P3–Pd2+ complex can be turned on by the addition of thiophanate-methyl (TM) without the interference from other anions and pesticides. Thus, P3–Pd2+ complex can work as the novel Pd2+−mediated conjugated polymer-based fluorescent (CPF) chemosensors platform for thiophanate-methyl detection. The “on-off-on” sensing mechanism was supported by MALDI-TOF mass analysis, density functional theory (DFT) calculations and the association constants Ka fitting.

Au21S(SAdm)15: Crystal Structure, Mass Spectrometry, Optical Spectroscopy, and First-Principles Theoretical Analysis

Here we report X-ray crystal structure, spectroscopic and theoretical characterization of Au21S(SAdm)15 (SAdm = adamantanethiol). Single-crystal X-ray diffraction shows that the Au21S(SAdm)15 nanomolecule exhibits a Au12 cuboctahedral core missing one vertex surrounded by a single μ3 sulfur atom (sulfide), five bridging thiols, two additional Au atoms, one monomeric Au(SR)2, and two trimeric Au3(SR)4 staples, with the two trimeric staples being linked through a Au2(SR) unit with a thiolate ligand in μ4 coordination. Compositional, electronic, optical, and structural features of this compound are clarified via nanoelectrospray ionization mass spectrometry (nESI-MS), matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS), low-temperature UV–vis spectroscopy, and first-principles analysis.

Structures, energetics and magnetic properties of Au<sub>n</sub>SFe<sub>m</sub> and Au<sub>n</sub>Fe<sub>m</sub> clusters for m = 1-5 and n = 1-5, 12 and 32

Simulations of nanoscale systems are important from the understanding point of view of the physics and chemistry involved in describing observed phenomenon. This paper presents the results of systematic theoretical investigation of the structural and magnetic properties of gold-iron complexes at small size scale. Ab initio calculations are performed for AunFem with and without the presence of a sulfur atom, i.e., the clusters AunSFem, where n, m = 1 - 5. The study also includes Au6SFe and Au12Fe in order to investigate how the fully wrapped Fe atom responds to the Au atoms .The study mainly focuses on the geometrical and magnetic changes with a step by step removal of the sulfur atom as a function of the cluster size. It is found that average Au-Fe bond length is increased with increasing number of atoms in the cluster. An increase of Au-Fe bond length would have increased the magnetic moment of the Fe atom, but due to the hybridization of Au and Fe orbitals, the moment converges to about 3.00 μB. This value is higher than the magnetic moment of Fe atom in bulk gold. An enhanced magnetic moment is found on Fe atom even if it is fully wrapped by the Au12 octahedral cluster. From this study it is found that, the cluster stability is increased on the addition of a single sulfur atom to the AunFem clusters. A special stability is observed in Au4SFe, Au6SFe, Au12SFe and Au4SFe2 clusters as the sulfur atom in these clusters is found to be doubly bonded. Generally, the systematic studies on the small sized clusters show an enhanced magnetic moment on the iron atoms bonded to the gold atoms as compared to the corresponding bare iron clusters. This indicates that, the magnetic moment of iron atoms can be enhanced by a complete coating with gold atoms for practical applications. This complete coating can prevent iron from oxidation and may also prevent coalescence of iron clusters and formation of thromboses. The coupling of iron atoms in this work remains ferromagnetic irrespective of the number of gold atoms in the cluster.Keywords: Cluster, Magnetic moment, Coating, Nanoparticles.

Assembly, structure, and reactivity of Cu₄S and Cu₃S models for the nitrous oxide reductase active site, Cu(Z)*.

Bridging diphosphine ligands were used to facilitate the assembly of copper clusters with single sulfur atom bridges that model the structure of the Cu(Z)* active site of nitrous oxide reductase. Using bis(diphenylphosphino)amine (dppa), a [Cu(I)4(μ4-S)] cluster with N-H hydrogen bond donors in the secondary coordination sphere was assembled. Solvent and anion guests were found docking to the N-H sites in the solid state and in the solution phase, highlighting a kinetically viable pathway for substrate introduction to the inorganic core. Using bis(dicyclohexylphosphino)methane (dcpm), a [Cu(I)3(μ3-S)] cluster was assembled preferentially. Both complexes exhibited reversible oxidation events in their cyclic voltammograms, making them functionally relevant to the Cu(Z)* active site that is capable of catalyzing a multielectron redox transformation, unlike the previously known [Cu(I)4(μ4-S)] complex from Yam and co-workers supported by bis(diphenylphosphino)methane (dppm). The dppa-supported [Cu(I)4(μ4-S)] cluster reacted with N3(-), a linear triatomic substrate isoelectronic to N2O, in preference to NO2(-), a bent triatomic. This [Cu(I)4(μ4-S)] cluster also bound I(-), a known inhibitor of Cu(Z)*. Consistent with previous observations for nitrous oxide reductase, the tetracopper model complex bound the I(-) inhibitor much more strongly and rapidly than the substrate isoelectronic to N2O, producing unreactive μ3-iodide clusters including a [Cu3(μ3-S)(μ3-I)] complex related to the [Cu4(μ4-S)(μ2-I)] form of the inhibited enzyme.

First principles calculation of adsorption for H2S on Fe(100) surface

In contrast to the results of sulfur atom adsorption, the adsorption of hydrogen sulfide on the Fe(100) surface has been studied using first principles method, which is based on the density functional theory (DFT). The structures, electronic properties were calculated by the generalized gradient approximation (GGA) for the coverage of 0.25 monolayer (ML). The results show that the H2S adsorbed on B2 site is stable and the adsorption energy is -1.23 eV and the structure of H2S is little changed. While the density of states (DOS) for the adsorption of hydrogen sulfide in the most unstable state after the adsorption at B1 and most stable adsorption at the site of B2 are analyzed. We have compared, under same conditions, the electronic properties of the sulfur atoms of the adsorbed hydrogen sulfide and a single sulfur atom adsorbed on Fe(100) surface. The adsorption effect is very weak for sulfur atoms in adsorbed hydrogen sulfide. At the same time, the density of states for the adsorption of Fe(100) surface was studied comparatively, and we found that the sulfur atom adsorption on Fe(100) showed a series of peaks that have discrete distributions generated by ferrous sulfide. It shows that the adsorption is given by sulfur atoms instead of molecules of hydrogen sulfide.

Electrochemical and spectroscopic effects of mixed substituents in bis(phenolate)-copper(II) galactose oxidase model complexes.

Nonsymmetric substitution of salen (1(R(1),R(2))) and reduced salen (2(R(1),R(2))) Cu(II)-phenoxyl complexes with a combination of -(t)Bu, -S(i)Pr, and -OMe substituents leads to dramatic differences in their redox and spectroscopic properties, providing insight into the influence of the cysteine-modified tyrosine cofactor in the enzyme galactose oxidase (GO). Using a modified Marcus-Hush analysis, the oxidized copper complexes are characterized as Class II mixed-valent due to the electronic differentiation between the two substituted phenolates. Sulfur K-edge X-ray absorption spectroscopy (XAS) assesses the degree of radical delocalization onto the single sulfur atom of nonsymmetric [1((t)Bu,SMe)](+) at 7%, consistent with other spectroscopic and electrochemical results that suggest preferential oxidation of the -SMe bearing phenolate. Estimates of the thermodynamic free-energy difference between the two localized states (ΔG(o)) and reorganizational energies (λ(R(1)R(2))) of [1(R(1),R(2))](+) and [2(R(1),R(2))](+) lead to accurate predictions of the spectroscopically observed IVCT transition energies. Application of the modified Marcus-Hush analysis to GO using parameters determined for [2(R(1),R(2))](+) predicts a ν(max) of ∼13600 cm(-1), well within the energy range of the broad Vis-NIR band displayed by the enzyme.

Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase

Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism.

Molecular characterization of effluent organic matter identified by ultrahigh resolution mass spectrometry

Effluent dissolved organic matter (EfOM) collected from the secondary-treated wastewater of the Orange County Sanitation District (OCSD) located in Fountain Valley, California, USA was compared to natural organic matter collected from the Suwannee River (SRNOM), Florida using ultrahigh resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Furthermore, the two different treatment processes at OCSD, activated sludge and trickling filter, were separately investigated. The blend of these two effluents was further evaluated after it had passed through the microfiltration process of the Advanced Water Purification Facility (AWPF) at Orange County Water District (OCWD). EfOM contained 872 different m/ z peaks that were unambiguously assigned to exact molecular formulae containing a single sulfur atom and carbon, hydrogen and oxygen atoms (CHOS formulae). In contrast, the SRNOM sample only contained 152 CHOS formulae. The trend in CHO molecular compositions was opposite with 2500 CHO formulae assigned for SRNOM but only about 1000 for EfOM. The CHOS-derived mass peaks with highest abundances in EfOM could be attributed to surfactants such as linear alkyl benzene sulfonates (LAS), their co-products dialkyl tetralin sulfonates (DATS) and their biodegraded metabolites such as sulfophenyl carboxylic acids (SPC). The differences between the treatments were found minor with greater differences between sampling dates than treatment methods used.

The Role of Cys-298 in Aldose Reductase Function

Diabetic tissues are enriched in an "activated" form of human aldose reductase (hAR), a NADPH-dependent oxidoreductase involved in sugar metabolism. Activated hAR has reduced sensitivity to potential anti-diabetes drugs. The C298S mutant of hAR reproduces many characteristics of activated hAR, although it differs from wild-type hAR only by the replacement of a single sulfur atom with oxygen. Isothermal titration calorimetry measurements revealed that the binding constant of NADPH to the C298S mutant is decreased by a factor of two, whereas that of NADP(+) remains the same. Similarly, the heat capacity change for the binding of NADPH to the C298S mutant is twice increased; however, there is almost no difference in the heat capacity change for binding of the NADP(+) to the C298S. X-ray crystal structures of wild-type and C298S hAR reveal that the side chain of residue 298 forms a gate to the nicotinamide pocket and is more flexible for cysteine compared with serine. Unlike Cys-298, Ser-298 forms a hydrogen bond with Tyr-209 across the nicotinamide ring, which inhibits movements of the nicotinamide. We hypothesize that the increased polarity of the oxidized nicotinamide weakens the hydrogen bond potentially formed by Ser-298, thus, accounting for the relatively smaller effect of the mutation on NADP(+) binding. The effects of the mutant on catalytic rate constants and binding constants for various substrates are the same as for activated hAR. It is, thus, further substantiated that activated hAR arises from oxidative modification of Cys-298, a residue near the nicotinamide binding pocket.

Oxidation of lanthionines renders the lantibiotic nisin inactive.

The peptide antibiotic nisin A belongs to the group of antibiotics called lantibiotics. They are classified as lantibiotics because they contain the structural group lanthionine. Lanthionines are composed of a single sulfur atom that is linked to the beta-carbons of two alanine moieties. These sulfur atoms are vulnerable to environmental oxidation. A mild oxidation reaction was performed on nisin A to determine the relative effects it would have on bioactivity. High-mass-accuracy Fourier transform ion cyclotron resonance mass spectrometry data revealed the addition of seven, eight, and nine oxygens. These additions correspond to the five lanthionines, two methionines, and two histidines that would be susceptible to oxidation. Subsequent bioassays revealed that the oxidized form of nisin A had a complete loss of bactericidal activity. In a competition study, the oxidized nisin did not appear to have an antagonistic affect on the bioactivity of nisin A, since the addition of an equal molar concentration of the oxidized variant did not have an influence on the bactericidal activity of the native antibiotic. Electron microscopy data revealed that the oxidized forms were still capable of assembling into large circular complexes, demonstrating that oxidation does not disrupt the lateral assembly mechanism of the antibiotic. Affinity thin-layer chromatography and fluorescence microscopy experiments suggested that the loss of activity is due to the inability of the oxidized form of nisin to bind to the cell wall precursor lipid II. Given the loss of bioactivity following oxidation, oxidation should be an important factor to consider in future production, purification, pharmacokinetic, and pharmacodynamic studies.

Effect of sulphur doping on manganese clusters: an ab initio study

We report a structural, electronic and magnetic analysis of minimal MnnS clusters, n = 1–13, from ab initio calculations. Total geometry optimizations were performed by considering compact manganese clusters, doped with a single sulphur atom. The doping was added to the cluster by considering substitution, interstitial and adsorbed positions. To further investigate the influence of the sulphur doping on the magnetic properties of manganese clusters, we performed non collinear magnetic calculations within the local spin density approximation (LSDA) for the exchange-correlation. We find that the electronic properties can be better controlled when the cluster is doped with a sulphur atom, and less size dependent. There are no differences in the magnetic properties of doped and non-doped clusters, except for n=7 and 8, in which the total magnetic moment per atom are smaller in doped clusters.