Unveiling the tyrosinase inhibitory potential of phenolics from Centaurium spicatum: Bridging in silico and in vitro perspectives.

Phenolics, abundant in plants, constitute a significant portion of phytoconstituents consumed in the human diet. The phytochemical screening of the aerial parts of Centaurium spicatum led to the isolation of five phenolics. The anti-tyrosinase activities of the isolated compounds were assessed through a combination of in vitro experiments and multiple in silico approaches. Docking and molecular dynamics (MD) simulation techniques were utilized to figure out the binding interactions of the isolated phytochemicals with tyrosinase. The findings from molecular docking analysis revealed that the isolated phenolics were able to bind effectively to tyrosinase and potentially inhibit substrate binding, consequently diminishing the catalytic activity of tyrosinase. Among isolated compounds, cichoric acid displayed the lowest binding energy and the highest extent of polar interactions with the target enzyme. Analysis of MD simulation trajectories indicated that equilibrium was reached within 30 ns for all complexes of tyrosinase with the isolated phenolics. Among the five ligands studied, cichoric acid exhibited the lowest interaction energies, rendering its complex with tyrosinase the most stable. Considering these collective findings, cichoric acid emerges as a promising candidate for the design and development of a potential tyrosinase inhibitor. Furthermore, the in vitro anti-tyrosinase activity assay unveiled significant variations among the isolated compounds. Notably, cichoric acid exhibited the most potent inhibitory effect, as evidenced by the lowest IC50 value (7.92 ± 1.32 µg/ml), followed by isorhamnetin and gentiopicrin. In contrast, sinapic acid demonstrated the least inhibitory activity against tyrosinase, with the highest IC50 value. Moreover, cichoric acid exhibited a mixed inhibition mode against the hydrolysis of l-DOPA catalyzed by tyrosinase, with Ki value of 1.64. Remarkably, these experimental findings align well with the outcomes of docking and MD simulations, underscoring the consistency and reliability of our computational predictions with the actual inhibitory potential observed in vitro.

Deciphering the Molecular Mechanisms of Reactive Metabolite Formation in the Mechanism-Based Inactivation of Cytochrome p450 1B1 by 8-Methoxypsoralen and Assessing the Driving Effect of phe268.

This study provides a comprehensive computational exploration of the inhibitory activity and metabolic pathways of 8-methoxypsoralen (8-MP), a furocoumarin derivative used for treating various skin disorders, on cytochrome P450 (P450). Employing quantum chemical DFT calculations, molecular docking, and molecular dynamics (MD) simulations analyses, the biotransformation mechanisms and the active site binding profile of 8-MP in CYP1B1 were investigated. Three plausible inactivation mechanisms were minutely scrutinized. Further analysis explored the formation of reactive metabolites in subsequent P450 metabolic processes, including covalent adduct formation through nucleophilic addition to the epoxide, 8-MP epoxide hydrolysis, and non-CYP-catalyzed epoxide ring opening. Special attention was paid to the catalytic effect of residue Phe268 on the mechanism-based inactivation (MBI) of P450 by 8-MP. Energetic profiles and facilitating conditions revealed a slight preference for the C4'=C5' epoxidation pathway, while recognizing a potential kinetic competition with the 8-OMe demethylation pathway due to comparable energy demands. The formation of covalent adducts via nucleophilic addition, particularly by phenylalanine, and the generation of potentially harmful reactive metabolites through autocatalyzed ring cleavage are likely to contribute significantly to P450 metabolism of 8-MP. Our findings highlight the key role of Phe268 in retaining 8-MP within the active site of CYP1B1, thereby facilitating initial oxygen addition transition states. This research offers crucial molecular-level insights that may guide the early stages of drug discovery and risk assessment related to the use of 8-MP.

Ionization, intrinsic basicity, and intrinsic acidity of unsaturated diols of astrochemical interest: 1,1- and 1,2-ethenediol: A theoretical survey.

The structure, stability, and bonding characteristics of 1,1- and 1,2-ethenediol, their radical cations, and their protonated and deprotonated species were investigated using high-level ab initio G4 calculations. The electron density of all the neutral and charged systems investigated was analyzed using the QTAIM, ELF, and NBO approaches. The vertical ionization potential (IP) of the five stable tautomers of 1,2-ethenediol and the two stable tautomers of 1,1-ethenediol go from 11.81 to 12.27 eV, whereas the adiabatic ones go from 11.00 to 11.72 eV. The adiabatic ionization leads to a significant charge delocalization along the O-C-C-O skeleton. The most stable protonated form of (Z)-1,2-ethenediol can be reached by the protonation of both the anti-anti and the syn-anti conformers, whereas the most stable deprotonated form arises only from the syn-anti one. Both charged species are extra-stabilized by the formation of an O-H···O intramolecular hydrogen bond (IHB) which is not found in the neutral system. (Z)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its cis-glycolaldehyde isomer. The most stable protonated species of (E)-1,2-ethenediol comes from its syn-syn conformer, although the anti-anti conformer is the most basic one. Contrarily, the three conformers yield a common deprotonated species, so their acidity follows exactly their relative stability. Again, the (E)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its trans-glycolaldehyde isomer. Neither the neutral nor the protonated or the deprotonated forms of 1,1-ethenediol show the formation of any O-H···O IHB. The most stable protonated species is formed by the protonation of any of the two tautomers, but the most stable deprotonated form arises exclusively from the syn-anti neutral conformer. The conformers of 1,1-ethenediol are much less stable and significantly less basic than their isomer, acetic acid, and only slightly more acidic.

Mechanistic aspects of reactive metabolite formation in clomethiazole catalyzed biotransformation by cytochrome P450 enzymes.

Clomethiazole (CLM), a sedative and anticonvulsant drug, is commonly employed for the treatment of alcohol withdrawal syndrome because it suppresses cytochrome P450 (P450) activity associated with the generation of free radicals and liver damage. The catalyzed biotransformation of thiazole-containing drugs by P450 is known to afford reactive metabolites. These metabolites can alter the biological functions of macromolecules and result in toxicity and adverse drug interactions. Multitargeted molecular modeling and quantum chemical DFT calculations were performed to explore the binding modes and molecular mechanisms underlying the mechanism-based inactivation (MBI) of P450 by CLM. The mechanistic details associated with reactive metabolite formation from further metabolic processes were extensively assessed. Seven possible routes were proposed for CLM-P450 biotransformation including CLM hydroxylation, sulfoxidation, N-oxidation, CN epoxidation (oxaziridine formation), and CC epoxidation. The results revealed a degree of preference for the C-N epoxidation pathway because of the low energy requirements of its rate-determining step (8.74 and 10.07 kcal mol-1 for LS and HS states, respectively). A kinetic competition for the CLM-methyl hydroxylation pathway was detected because the H-abstraction energy barrier was relatively comparable to the thermodynamically prevailing oxaziridine formation rate-determining step (12.58 and 14.52 kcal mol-1 for quartet and doublet states, respectively). Our studies assessed the mechanisms of covalent nucleophilic epoxide adduct formation through nucleophilic addition, hydrolysis of epoxidation products, and nonenzymatic degradation. CLM was shown to display P450-inhibitory activity by forming covalent adducts rather than further metabolization to reactive metabolites. The outcomes of molecular docking allowed assessing the binding profile of CLM with three human P450 isozymes, namely, CYP2E1, CYP3A4, and CYP2D6.

Molecular modeling and DFT studies on the antioxidant activity of Centaurea scoparia flavonoids and molecular dynamics simulation of their interaction with ß-lactoglobulin.

Plants of the genus Centaurea have been widely used as natural therapeutics in different countries. This study investigated the antioxidant-structure activity relationship of eight flavonoids isolated from Centaurea scoparia using DFT studies and in vitro radical scavenging and xanthine oxidase (XO) inhibition assays, and to correlate the theoretical values with the experimental findings. Docking analysis was carried out to explore the binding modes of the isolated phytochemicals with XO and bovine ß-lactoglobulin (BLG). Interactions of the isolated compounds with BLG were studied using molecular dynamics (MD) simulations which revealed the involvement of hydrogen bonding. The root-mean-square deviation (RMSD) of BLG and BLG-flavonoid complexes reached equilibrium and fluctuated during the 10 ns MD simulations. The radius of gyration (Rg) and solvent accessible surface area (SASA) revealed that various systems were stabilized at approximately 2500 ps. In addition, the RMS fluctuations profile indicated that the ligand's active site exerted rigidity behavior during the simulation. The hydrogen atom transfer (HAT) and the energies of hydrogen abstractions were estimated by calculating the bond dissociation enthalpy (BDE) of O-H in gas phase and water. The isolated compounds showed radical scavenging and XO inhibitory activities along with binding affinity with XO as revealed in silico. The BDE was linked to the radical scavenging processes occurring in polar solvents. These processes are single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). Our calculations indicated the agreement between the calculated results and the experimentally measured antioxidant activity of the flavonoids isolated from C. scoparia.

Open questions on toxic heavy metals Cd, Hg and Pb binding small components of DNA and nucleobases. Are there any predictable trends?

In this perspective article, we provide a bibliographic compilation of experimental and theoretical work on Cd, Hg, and Pb, and analyze in detail the bonding of M2+ and CH3M+ (M = Zn, Cd, Hg, Pb) with urea and thiourea as suitable models for larger biochemical bases. Through the use of DFT calculations, we have found that although in principle binding energies decrease according to ionic size (Zn2+ > Cd2+ > Pb2+), Hg2+ largely breaks the trend. Through the use of EDA (Energy Decomposition Analysis) it is possible to explain this behavior, which is essentially due to the strong contribution of polarization to the binding. This conclusion is ratified by the NEDA (Natural Energy Decomposition Analysis) formalism, showing that the charge transfer term is very large in all cases, but particularly in the case of the mercury-thiourea system. The general trends observed for the interactions with CH3M+ monocations show however CH3Hg+ binding energies systematically smaller than the CH3Zn+ ones, likely because the relativistic contraction of the Hg orbitals is very much attenuated by the attachment to the methyl group. Finally, we have investigated the gas-phase reactivity between EtHg+ and uracil to compare it with that exhibited by CH3Hg+ and n-ButHg+ previously described in the literature. This comparison gathers new information that highlights the importance of the length of the alkyl chain attached to the metal on the mechanisms of these reactions. For methyl mercury, only the alkyl transfer process is allowed; for butyl mercury, protonation is clearly favored, and for ethyl mercury, both paths are competitive experimentally.

Xanthine Oxidase Inhibitory Activity of Euphorbia peplus L. Phenolics.

BACKGROUND: Various phenolics show inhibitory activity towards xanthine oxidase (XO), an enzyme that generates reactive oxygen species which cause oxidative damage. OBJECTIVE: This study investigated the XO inhibitory activity of Euphorbia peplus phenolics. METHODS: The dried powdered aerial parts of E. peplus were extracted, fractioned and phenolics were isolated and identified. The XO inhibitory activity of E. peplus extract (EPE) and the isolated phenolics was investigated in vitro and in vivo. RESULTS: Three phenolics were isolated from the ethyl acetate fraction of E. peplus. All isolated compounds and the EPE showed inhibitory activity towards XO in vitro. In hyperuricemic rats, EPE and the isolated phenolics decreased uric acid and XO activity. Molecular docking showed the binding modes of isolated phenolics with XO, depicting significant interactions with the active site amino acid residues. Molecular dynamics simulation trajectories confirmed the interaction of isolated phenolics with XO by forming hydrogen bonds with the active site residues. Also, the root mean square (RMS) deviations of XO and phenolics-XO complexes achieved equilibrium and fluctuated during the 10 ns MD simulations. The radius of gyration and solvent accessible surface area investigations showed that different systems were stabilized at ≈ 2500 ps. The RMS fluctuations profile depicted that the drug binding site exhibited a rigidity behavior during the simulation. CONCLUSION: In vitro, in vivo and computational investigations showed the XO inhibitory activity of E. peplus phenolics. These phenolics might represent promising candidates for the development of XO inhibitors.

Water biocatalytic effect attenuates cytochrome P450-mediated carcinogenicity of diethylnitrosamine: A computational insight.

The mechanism-based mutagenicity and carcinogenicity of diethylnitrosamine (DEN) are believed to act through interactions with cytochrome P450 (P450) enzymes. DFT calculations to explore the conceivable mechanisms underlying the reaction of P450 with DEN with and without water as a biocatalyst were performed. The results shed light on the biocatalytic role of water in lowering the H-abstraction energy barriers because of the electrostatic effect driven by hydrogen bonding. Our DFT analysis revealed how metabolites are formed in the dealkylation (toxification) and denitrosation (detoxification) pathways. Also, our findings uncovered the active position of DEN vulnerable to P450 interactions. Two factors control the toxification and detoxification rates: the stability of denitrosation products and the HS rebound barrier of the α-pathway. Thus, water biocatalytic attenuation of DEN carcinogenicity was attained by stabilizing denitrosation products and slowing the α-HS rebound process. Docking and MD simulations were performed to assess the binding modes of DEN to P450's active site and to inspect the denitrosation and dealkylation processes, respectively.

Perturbating Intramolecular Hydrogen Bonds through Substituent Effects or Non-Covalent Interactions.

An analysis of the effects induced by F, Cl, and Br-substituents at the α-position of both, the hydroxyl or the amino group for a series of amino-alcohols, HOCH2(CH2)nCH2NH2 (n = 0-5) on the strength and characteristics of their OH···N or NH···O intramolecular hydrogen bonds (IMHBs) was carried out through the use of high-level G4 ab initio calculations. For the parent unsubstituted amino-alcohols, it is found that the strength of the OH···N IMHB goes through a maximum for n = 2, as revealed by the use of appropriate isodesmic reactions, natural bond orbital (NBO) analysis and atoms in molecules (AIM), and non-covalent interaction (NCI) procedures. The corresponding infrared (IR) spectra also reflect the same trends. When the α-position to the hydroxyl group is substituted by halogen atoms, the OH···N IMHB significantly reinforces following the trend H < F < Cl < Br. Conversely, when the substitution takes place at the α-position with respect to the amino group, the result is a weakening of the OH···N IMHB. A totally different scenario is found when the amino-alcohols HOCH2(CH2)nCH2NH2 (n = 0-3) interact with BeF2. Although the presence of the beryllium derivative dramatically increases the strength of the IMHBs, the possibility for the beryllium atom to interact simultaneously with the O and the N atoms of the amino-alcohol leads to the global minimum of the potential energy surface, with the result that the IMHBs are replaced by two beryllium bonds.

The quasi-irreversible inactivation of cytochrome P450 enzymes by paroxetine: a computational approach.

The mechanism-based inactivation (MBI) of P450 by paroxetine was investigated by computational analysis. The drug-enzyme interactions were figured out through studying energy profiles of three competing mechanisms. The potency of paroxetine as P450's inhibitor was estimated based on the availability of two active sites for the MBI in the paroxetine structure. The inactivation by the amino site of paroxetine mainly proceeds via the hydrogen atom transfer pathway because of the lower energy demand of its rate determining step. In addition, the low-spin state is the predominant route in the MBI at the methylenedioxo active site as a result of being rebound barrier-free mechanism. Our comparative investigation showed that inactivation at the secondary amine is thermodynamically more favorable because of the lower energy barrier of the dehydration mechanism of the hydroxylated paroxetine complex than its methylenedioxo counterpart. The results of docking analysis coincided with the outputs of DFT calculations since the docking pose with the lowest binding affinity is that for conformation with polar interaction between the amino group of paroxetine and the oxo moiety of P450's active site. Assessment of the molecular dynamics simulations trajectories revealed the favorable interaction of paroxetine with P450.

On the nature of the interaction of copper hydride and halide with substituted ethylene and acetylene.

The association of Cu-X (X = -H, -Cl, and -F) with H2CCHCHmYn and HCCCHmYn (Y = -Cl, -F, -OH, -CH3) has been studied at a high level of theory. The density functional theory (DFT) at B3LYP/6-311G(d,p)//B3LYP/6-311 + G(3df,2p) level has been chosen to calculate the structure and the relative stability of 24 different complexes. The interaction of Cu-F with the derivatives of ethylene and acetylene was found very strong, with interaction energies close to those of conventional covalent bonds. In all complexes, the most stable structure was found when Cu-X is positioned on the unsaturated CC bond, forming a three-membered ring that leads to longer CC bond distances. Both ethylene and acetylene complexes show similar trends of interaction energies with respect to the same moiety. All electronic indexes analyzed by means of the QTAIM, ELF, and NBO formalisms indicate that the strength of the interaction should increase with the number of withdrawing substituents in both series of compounds. Graphical abstractThe p-Interaction of ethylene and acetylene derivative with fluoride copper. The ELF graphs and its 2D projection show the disynaptic basins of the electrostatic binding.

Rumex dentatus L. phenolics ameliorate hyperglycemia by modulating hepatic key enzymes of carbohydrate metabolism, oxidative stress and PPARγ in diabetic rats.

Rumex dentatus L. is a flowering plant with promising therapeutic effects. This study investigated the antioxidant efficacy of phenolic compounds isolated from R. dentatus L. in vitro and by conducting density function theory (DFT) studies to explore the mechanisms of action. The antioxidant, anti-inflammatory and antidiabetic effects of polyphenols-rich R. dentatus extract (RDE) were investigated in type 2 diabetic rats. Phytochemical investigation of the aerial parts of R. dentatus resulted in the isolation of one new and seven known compounds isolated for the first time from this species. All isolated phenolics showed in vitro radical scavenging activity. The antioxidant activity of the compounds could be oriented by the hydrogen atom transfer and sequential proton loss electron transfer mechanisms in gas and water phases, respectively. In diabetic rats, RDE attenuated hyperglycemia, insulin resistance and liver injury and improved carbohydrate metabolism. RDE suppressed oxidative stress and inflammation and upregulated PPARγ. In silico molecular docking analysis revealed the binding affinity of the isolated compounds toward PPARγ. In conclusion, the computational calculations were correlated with the in vitro antioxidant activity of R. dentatus derived phenolics. R. dentatus attenuated hyperglycemia, liver injury, inflammation and oxidative stress, improved carbohydrate metabolism and upregulated PPARγ in diabetic rats.

Reaction Mechanism of Li and Mg Carbenoid Cyclopropanations: Metal-π and σ Interactions.

The mechanism of the reaction of lithium and magnesium carbenoids with ethylene to give cyclopropane has been explained in detail in all the steps at the G4 level of theory. We explored the lithium and magnesium interaction toward πC=C and σC-C bonds in the reactants and the products. We have also investigated the reaction path by means of the force profile formalism in order to highlight the electronic and the structural rearrangements along the potential energy surface of the cyclopropanation. The results indicate that all of the reactions are stepwise, exoenergetic, with low barriers. All our findings were confirmed by dynamic simulations for chlorometal carbenoids. Furthermore, from the intrinsic reaction coordinate procedure, we were able to find out the intermediates that can take place when the reaction is descending from the transition state to the products or reactants. The reaction force analysis at B3LYP/6-311G(d,p) indicates that the energy barriers are mostly due to structural rearrangements which are produced by the approach of the carbenoid to ethylene. Quantum theory of atoms in molecules and electron localization function analyses indicate that products, reactants, and intermediates form complexes stabilized by attractive forces between Li/Mg and single/double bonds.

Combined Experimental and Theoretical Survey of the Gas-Phase Reactions of Serine-Ca2+ Adducts.

The association of Ca2+ to serine and the subsequent gas-phase unimolecular reactivity of the [Ca(Ser)]2+ (Ser = Serine) adduct was investigated throughout the use of tandem mass spectrometry techniques and B3LYP/6-311+G(3df,2p)//B3LYP/6-311+G(d,p) density functional theory calculations. In a first step, the structure and relative stability of all possible conformers of serine were obtained and analyzed, as well as the most stable [serine-Ca]2+ adducts. For the analysis of the different potential energy surfaces associated with the gas-phase unimolecular reactivity of these adducts, only those that differ by less than 100 kJ·mol-1 from the global minimum were taken into account. In agreement with previous studies, the serine-Ca2+ global minimum corresponds to a charge-solvated structure in which Ca is tricoordinated to neutral serine. The major peaks observed in the nanoelectrospray-MS/MS spectrum of [Ca(Ser)]2+ adduct correspond to both Coulomb explosions, yielding either CaOH+ + [C3,H6,N,O2]+ or [C2,H4,O,N]+ + [Ca(C,H3,O2)]+, and to the loss of neutrals, namely, CH2O and H2O. Our theoretical survey of the energy profile allow us to conclude that, although all the aforementioned fragmentation processes can have their origin at the global minimum, similar fragmentations involving low-lying conformers, both zwitterionic and nonzwitterionic, compete and should be considered to account for the observed reactivity. We have also found that in some specific cases post-transition state dynamics similar to the ones described before in the literature for formamide-Ca2+ reactions, may also play a role.

Reduction of C[double bond, length as m-dash]O functional groups through H addition reactions: a comparative study between H2CO + H, CH3CH2CHO + H and CH3OCHO + H under interstellar conditions.

H-addition reactions on the icy interstellar grains may play an important role in the formation of complex organic molecules. In the present work we propose a comparative study of H2CO + H, CH3CH2CHO + H and CH3OCHO + H solid state reactions at 10 K under interstellar conditions in order to characterize the main reaction pathways involved in the hydrogenation of a CHO functional group. We show that the most probable mechanism for the formation of alcohols under non-energetic conditions through the saturation of the CHO group corresponds to the attachment of the H atom to the CH group with noticeable variations of the energy barriers for each studied reaction. These energy barriers have been calculated to be 8.3, 14.6 and 32.7 kJ mol-1 for H2CO + H, CH3CH2CHO + H and CH3OCHO + H, respectively. The coupling of the experimental and theoretical analysis proves that while the simplest aldehyde, formaldehyde, is easily reduced to methanol, methylformate and propanal behave differently under H-bombardments but they cannot be a source of alcohol formation through H-addition reactions. Consequently, for the formation of alcohols larger than CH3OH, other chemical pathways should be taken into account, probably energetic processing such as the photolysis of interstellar ice analogues containing C-, H- and O-bearing compounds or the coupling of the H-addition reaction and photon-irradiation on species with a CHO functional group.

Computational Study of the Structure and Degradation Products of Alloxydim Herbicide.

Density functional theory calculations allowed us to study alloxydim herbicide and to identify the most stable conformers, the factors that governs their stability, and the interconversion mechanisms among the most relevant conformers. The degradation chain involves, as a first step, the cleavage of the N-O bond and the formation of a stable intermediate difficult to characterize experimentally. The study performed also allowed us to identify the properties of this elusive intermediate and to determine that the dominant fragmentation process in the gas phase is the homolytic fragmentation. Stability of alloxydim conformers and homolytic fragments were also assessed in the water phase. Computed IR spectra were consistent with those observed experimentally.

A Computational Study of the Reactivity of 3,5-(Oxo/Thioxo) Derivatives of 2,7-Dimethyl-1,2,4-Triazepines. Keto-Enol Tautomerization and Potential for Hydrogen Storage.

The G4 level of theory was used to evaluate the acidity of a series of triazepines, that is, 3-thioxo-5-oxo-, 5-thioxo-3-oxo-, 3,5-dioxo-, and 3,5-dithioxo- derivatives of 2,7-dimethyl-[1,2,4]-triazepine. The ability of their available nitrogen lone pair to form a dative bond with BH3 was also studied to highlight the resulting changes in acidity and to understand the behavior of the complexes formed. The effect of the substitution of sulfur by oxygen on the stability of the complex and the activation barrier of dehydrogenation was also evaluated. The formation of these triazepine:BH3 complexes, accompanied by the loss of H2 molecular hydrogen, is a strongly exothermic process. With one triazepine the pathway for H2 elimination from [triazepine]-BH3 is characterized by a small energy barrier ranging from 11 to 23 kJ/mol. The second H2 elimination is relatively more energetic than the first one (∼27 kJ/mol). Because of the steric hindrance associated with the addition of two molecules of triazepine (triazepine)2-BH2, the third dehydrogenation step is relatively less favorable than the two preceding steps, particularly in the case of the 3,5-dithio- derivative. The potential energy surface associated with the dehydrogenation reaction of all triazepine derivatives was explored. The thermodynamic favorability reported in this study could allow triazepine-borane to be used as a material for H2 storage applications.

Interactions of Dimethyltin(IV) with Uracil As Studied in the Gas Phase.

The gas-phase interactions of uracil (Ura) with dimethyltin(IV) were studied by a combined experimental and theoretical approach. Positive-ion electrospray spectra show that the interaction of dimethyltin(IV) with Ura results in the formation of the [(CH3)2Sn(Ura-H)]+ ion. The tandem mass spectrometry spectrum of this complex is characterized by numerous fragmentation processes, notably associated with elimination of H,N,C,O and C3,H3,N,O moieties, as well as the unusual loss of C2H6 leading to the [Sn(Ura-H)]+ complex. In turn, the [Sn(Ura-H)]+ complex fragments according to pathways already observed for the [Pb(Ura-H)]+ analogue. Sequential losses of ·CH3 radicals are also observed from the [(CH3)2Sn(N,C,O)]+ species (m/z 192). Comparison between density functional theory-computed vibrational spectra and the infrared multiple photon dissociation spectrum recorded between 1000 and 1900 cm-1 shows a good agreement as far as the global minimum is concerned. This comparison points to a bidentate interaction with a deprotonated canonical diketo form of uracil, involving both the N3 and O4 electronegative centers. This binding scheme has been already reported for the Pb/uracil system. The bidentate form characterized by the interaction between dimethyltin with N3 and O2 centers is slightly less stable. Interconversion between the two structures is associated with a small activation barrier (56 kJ/mol). The potential energy surfaces were explored to account for the main fragmentations observed upon collision-induced dissociation.

Quantum chemistry in environmental pesticide risk assessment.

The scientific community and regulatory bodies worldwide, currently promote the development of non-experimental tests that produce reliable data for pesticide risk assessment. The use of standard quantum chemistry methods could allow the development of tools to perform a first screening of compounds to be considered for the experimental studies, improving the risk assessment. This fact results in a better distribution of resources and in better planning, allowing a more exhaustive study of the pesticides and their metabolic products. The current paper explores the potential of quantum chemistry in modelling toxicity and environmental behaviour of pesticides and their by-products by using electronic descriptors obtained computationally. Quantum chemistry has potential to estimate the physico-chemical properties of pesticides, including certain chemical reaction mechanisms and their degradation pathways, allowing modelling of the environmental behaviour of both pesticides and their by-products. In this sense, theoretical methods can contribute to performing a more focused risk assessment of pesticides used in the market, and may lead to higher quality and safer agricultural products. © 2017 Society of Chemical Industry.

Gas-phase interactions of organotin compounds with cysteine.

The gas-phase interactions of cysteine with di-organotin and tri-organotin compounds have been studied by mass spectrometry experiments and quantum calculations. Positive-ion electrospray spectra show that the interaction of di- and tri-organotins with cysteine results in the formation of [(R)2 Sn(Cys-H)]+ and [(R)3 Sn(Cys)]+ ions, respectively. MS/MS spectra of [(R)2 Sn(Cys-H)]+ complexes are characterized by numerous fragmentation processes, notably associated with elimination of NH3 and (C,H2 ,O2 ). Several dissociation routes are characteristic of each given organic species. Upon collision, both the [(R)3 Sn(Gly)]+ and [(R)3 Sn(Cys)]+ complexes are associated with elimination of the intact amino acid, leading to the formation of [(R)3 Sn]+ cation. But for the latter complex, two additional fragmentation processes are observed, associated with the elimination of NH3 and C3 H4 O2 S. Calculations indicate that the interaction between organotins and cysteine is predominantly electrostatic but also exhibits a considerable covalent character, which is slightly more pronounced in tri-organotin complexes. A preferred bidentate interaction of the type -η2 -S-NH2 , with sulfur and the amino group, is observed. As for the [(R)3 Sn(Cys)]+ complexes, their stability is due to the combination of the hydrogen bond taking place between the amino group and the sulfur lone pair and the interaction between the carboxylic oxygen atom and the metal. Copyright © 2016 John Wiley & Sons, Ltd.