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Flaviviruses are among the most critical pathogens in tropical regions and cause a growing number of severe diseases in developing countries. The development of antiviral therapeutics is crucial for managing flavivirus outbreaks. Among the ten proteins encoded in the flavivirus RNA, non-structural protein 5, NS5, is a promising drug target. NS5 plays a fundamental role in flavivirus replication, viral RNA methylation, RNA polymerization, and host immune system evasion. Most of the NS5 inhibitor candidates target NS5 active sites. However, the similarity of NS5 activity sites with human enzymes can cause side effects. Identifying new allosteric sites in NS5 can contribute enormously to antiviral development. The NS5 structural characterization enabled exploring new regions, such as the residues involved in MTase-RdRp interaction, NS5 oligomerization, and NS5 interaction with other viral and host-cell proteins. Targeting NS5 critical interactions might lead to new compounds and overcomes the toxicity of current NS5-inhibitor candidates.

The methyltransferase (MTase) domain of non-structural protein 5 (NS5) plays a fundamental role in flaviviruses replication, and its inhibition is a strategy for antiviral development. MTase methylates viral RNA cap at guanine N-7 and the ribose 2'OH of the first adenosine. Many structures of Zika virus (ZIKV) and other flaviviruses MTases bound to cofactors, substrates and inhibitor candidates have been solved. Still, the dynamical modulation of MTase binding and catalytic activity yet needs to be clarified. Here, we investigated the structural dynamics of ZIKV NS5 MTase domain free and bound to Guanosine-5'-triphosphate (GTP) and

This paper employs gravimetric, potentiodynamic polarization and SEM methods to study the corrosion inhibition of mild steel in 1 M solution of hydrochloric acid using hexamethylenetetramine as an inhibitor. The results show that inhibition efficiency increases with concentration up to 86% at 0.8 g L−1 inhibitor dosage. The data obtain are consistent with the isotherm proposed by Langmuir. The values of both activation and Gibbs free energy show that adsorption is physisorption and spontaneous. DFT quantum calculations also support a physisorption process which validates that nitrogen atoms are the most reactive and nucleophilic atoms, which is consistent with the experimental results.

Based on density functional theory (DFT) electronic structure calculations with dispersion correction, we propose new reaction pathways in which no extra reaction step is necessary to account for the formation of 3,5,6-trichloro-2-pyridynol (TCP) within the process of tropospheric OH-initiated unimolecular decomposition of chlorpyrifos (CLP) and chlorpyrifos-methyl (CLPM). Chlorpyrifos and its analogous compound are among the most used organophosphorus pesticides worldwide, and their unimolecular decomposition in the troposphere is a dominant process of removal in the gas phase. The reaction pathways that we put forward have turned out to be the most exergonic ones among the three possible routes for the attack of the hydroxyl radical to the thiophosphoryl (P═S) bond of both CLP and CLPM. The results showed that the reaction is thermodynamically controlled with the formation of P-bonded adducts via a six-membered ring. The unimolecular decomposition of such reactive intermediates takes place with small energy barriers (less than 3 kcal mol

In this article, Density Functional Theory based calculations, including dispersion corrections, PBE0(D3BJ)/Def2-TZVP(-f), were performed to elucidate the photophysics of the [Ru(bpy)

A complete mechanism for the •OH-initiated atmospheric decomposition of the pesticides chlorpyrifos and chlorpyrifos-methyl is proposed, incorporating additional studies on the competing reaction with singlet oxygen. The computational study is based on density functional theory (DFT) at the double-hybrid functional level to treat static correlation in the calculations of energy barriers. Reaction of the P-bonded intermediate with 1O2 has a small energy barrier of ~ 2 kcal mol−1, generating the Oxone compound and the HOSO• radical, with a reaction free energy of − 49.8 kcal/mol for the chlorpyrifos reaction pathway. Direct reaction of the pesticides with singlet oxygen is unlikely to happen due to the exceedingly high energy barrier of ~ 52 kcal/mol. However, in aqueous solution, the activation energy reduces dramatically and changes the reaction thermodynamics, making it kinetically accessible and thermodynamically viable.

The chemical reactivity of NO and its role in several biological processes seem well established. Despite this, the chemical reduction of •NO toward HNO has been historically discarded, mainly because of the negative reduction potential of NO. However, this value and its implications are nowadays under revision. The last reported redox potential, E'(NO,H+/HNO), at micromolar and picomolar concentrations of •NO and HNO, respectively, is between -0.3 and 0 V at pH 7.4. This potential implies that the one-electron-reduction process for NO is feasible under biological conditions and could be promoted by well-known biological reductants with reduction potentials of around -0.3 to -0.5 V. Moreover, the biologically compatible chemical reduction of •NO (nonenzymatic), like direct routes to HNO by alkylamines, aromatic and pseudoaromatic alcohols, thiols, and hydrogen sulfide, has been extensively explored by our group during the past decade. The aim of this work is to use a kinetic modeling approach to analyze electrochemical HNO measurements and to report for the first-time direct reaction rate constants between •NO and moderate reducing agents, producing HNO. These values are between 5 and 30 times higher than the previously reported keff values. On the other hand, we also showed that reaction through successive attack by two NO molecules to biologically compatible compounds could produce HNO. After over 3 decades of intense research, the •NO chemistry is still there, ready to be discovered.

Photosensitizer (PS) molecules play a critical role in photodynamic therapy of cancer and the understanding of the molecular mechanism involved in the photophysics of these compounds, and their reactions in the excited state are, therefore, of great interest for the development of this technique. In this article, the photophysics of the cationic PS 4,5-dibromorodamine methyl ester (TH9402), its electron- and energy-transfer reactions in the excited triplet state, with molecular oxygen, nitric oxide, guanosine-5'-monophosphate (GMP), and guanine, and the interaction with DNA were evaluated. Time-dependent density functional theory calculations at the TPSSh/Def2-TZVP//B3LYP/Def2-TZVP level of theory in water solution reveals that the PS has a bright S1 state 2.33 eV above the ground state that produces a fluorescent rate constant of 5.40 × 107 s-1, calculated using Fermi's golden rule within a path integral formalism. Once excited to the bright state, the main intersystem crossing (ISC) channel involves the coupling with the T2 state just below S1 (S1 → T2 → T1) with an overall ISC rate constant of 10.1 × 107 s-1, in good agreement with the experimental data. Excited-state reaction thermodynamics, computed at the M06-2X/Def2-TZVP//B3LYP/Def2-TZVP level of theory in water, showed that from all the excited-state electron-transfer reactions studied, only the transfer from GMP to the PS is thermodynamically favorable, independent of the protonation state of guanosine, which indicates a possible DNA photo-oxidation mechanism for the PS. Triplet-triplet energy-transfer reactions from TH9402 to molecular oxygen, producing reactive singlet oxygen, and to the deprotonated guanosine, producing 3GMP2-, are also thermodynamically favorable, with ΔG = -2.0 and -24.0 kcal//mol, respectively. However, the energy transfer to the monoprotonated guanosine is not favorable, (ΔG = 36.1), suggesting that in the DNA double-strand environment, this energy-transfer process may not be observed. The results show that the PS can act through electron transfer and triplet-triplet energy-transfer reactions involved in mechanism types I and II in photodynamic therapy. Interactions of TH9402 with the d(AGACGTCT)2 octanucleotide revealed that the PS can intercalate between the d(GpC)-d(CpG) base pairs in three different orientations and, upon intercalation, the π → π* transition of the PS shows a bathochromic shift up to 90 nm and up to 60% decrease in intensity. Interactions through groove binding showed a smaller bathochromic shift of 52.2 nm and a 56% decrease in intensity of the main transition band.

Nitric oxide (NO) has well known vasodilation effects in living organisms and its participation in the metastasis of cancer cells through the angiogenesis process has been demonstrated experimentally. Therefore, the uptake of NO has become one focus of investigation to produce anti-metastatic drugs. In this article we have investigated the uptake of NO by the ruthenium based metallodrug trans-tetrachloride(dimethylsulfoxide)imidazole ruthenate(III) [Im]trans-[RuCl4(Im)(DMSO)], known as New Anti-tumor Metastasis Inhibitor-A (NAMI-A). Electronic structure calculations using Density Functional Theory, DFT, and State-Averaged Complete Active Space Self Consistent Field, SA-CASSCF, with second order perturbation theory corrections, NEVPT2 were carried out to investigate the mechanism involved in the uptake of NO by the Ru-based anticancer metallodrug NAMI-A. The calculations revealed that the reaction takes place at the triplet potential energy surface, with the singlet surface being ∼15 kcal mol−1 shifted to higher energies, and there is a surface crossing to form the most stable singlet product after the reaction takes place at the triplet surface. The spin pairing and electron transfer from the nitric oxide to the metallic fragment takes place at the region of the minimum energy crossing point between the two surfaces. The Ru–NO bond in the {Ru–NO}6 product has ∼10% of the RuIII–NO0 character. The SA-CASSCF/NEVPT2 calculations revealed that the uptake of NO by NAMI-A has a small energy barrier of ∼8 kcal mol−1 and, therefore a rate constant of 11.3 × 106 s−1 at 300 K. In addition, the reaction is thermodynamically favorable, with a Gibbs free energy of ∼30 kcal mol−1. These results show that the uptake of nitric oxide by the NAMI-A complex is kinetically and thermodynamically feasible in biological medium and, therefore, gives support to the anti-angiogenesis theory associated to the mode of action of NAMI-A and other related compounds.

In this work, a 8-hydroxyquinoline derivative, named 8-hydroxyquinoline-2-carboxaldehyde 2-furoyl hydrazone (HQFUH), was obtained. The respective compound was successfully synthesized as well as its respective Zn(II) coordination compound. Both compounds were structurally characterized, by experimental and theoretical IR and Raman spectra, XRD. Single crystal XRD showed that Zn(II) adopts a tetrahedral geometry, in which the neutral chelating ligand coordinates bidentaded by two N-atoms and the neutrality charge is achieved by two coordinated chloride ions. Topological analysis using Quantum Theory of Atoms in Molecules (QTAIM) was performed to investigate ligand interaction through O-atoms. This investigation is important regarding the determination of complex formation constant. The crystal structures of the ligand and complex are arranged according to an orthorhombic system with P212121 and Aea2 space groups, respectively. Ligand displays a E configuration around to C10 = N2 bond, while after the coordination of metal, a Z configuration is observed. Besides molecular structure description of complex, the intermolecular environment was analyzed by Hirshfeld Surface.

Complexes [Ag(H2BzPh)NO3] (1), [Ag(H2BzpCH3Ph)NO3] (2), [Ag(H2BzpClPh)NO3] (3), and [Ag(H2BzpNO2Ph)NO3] (4) were synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its para-methyl-benzoylhydrazone (H2BzpCH3Ph), para-chloro-benzoylhydrazone (H2BzpClPh), and para-nitro-benzoylhydrazone (H2BzpNO2Ph) derivatives. Experimental data indicate that the nitrate ligand binds more strongly to the silver center through one of the oxygen atoms, whereas the second oxygen atom from nitrate and the hydrazone oxygen makes much weaker interactions with the metal. Dissociation of nitrate most probably occurs in solution and in biological media. Interestingly, theoretical calculations suggested that when dissociation of the nitrate takes place, all bond orders involving the metal and the atoms from the hydrazone ligand increase significantly, showing that the bonding of nitrate results in the weakening of all other interactions in the metal coordination sphere. Upon complexation of the hydrazones to silver(I), cytotoxicity against B16F10 metastatic murine melanoma cells increased in all cases. Complexes (1–3) proved to be more cytotoxic than cisplatin. All compounds were more cytotoxic to B16F10 cells than to nontumorigenic murine Melan-A melanocyte cells. Interestingly, the selectivity index (SI = IC50 non-malignant cells/IC50 tumor cells) of complex (1), SI = 23, was much higher than that of the parent hydrazone ligand, SI = 9.5. Studies on the interactions of complexes (1–3) with DNA suggested that although (1–3) interact with calf thymus DNA by an intercalative mode, direct covalent binding of silver(I) to DNA probably does not occur. Complexes (1–3) interact in vitro with human serum albumin indicating that these compounds could be transported by albumin.

In the present work, density functional theory (DFT) calculations at the B3LYP/6-31+G(d) and including dispersion effects were used to investigate the hydrolysis of paraoxon, using a cluster model of the active site of Cd2+/Cd2+-phosphotriesterase (PTE) from Pseudomonas diminuta. The mechanism proposed here consist of (i) Exchange of the coordinated water molecule and coordination of the substrate to the more solvent exposed Cdβ center in monodentate fashion, (ii) protonation of the μ-hydroxo bridge by the uncoordinated water molecule and in situ formation of the nucleophile, (iii) formation of a pentacoordinate intermediate with significant bond breaking to the leaving group and bond formation to the nucleophile, and (iv) protonation of the Asp301 residue and restoration of the active site through the coordination of another water molecule of the medium. The water molecules initially coordinated to the active site play a crucial role in stabilizing the transition states and the pentacoordinate intermedia...

Complexes [Ag(H2AcPh)NO3] (1) [Ag(H2AcpCH3Ph)NO3] (2) [Ag(H2AcpClPh)NO3] (3) and [Ag(H2AcpNO2Ph)NO3] (4) were obtained with 2-acetylpyridinebenzoylhydrazone (H2AcPh) and its para-methyl-(H2AcpCH3Ph), para-chloro-(H2AcpClPh) and para-nitro-benzoylhydrazone (H2AcpNO2Ph) derivatives. In general, upon coordination to silver(I) the antimicrobial activity of the hydrazones increased against yeast and filamentous fungi. Several compounds proved to be as or more active than nystatin against the filamentous fungi. SAR studies showed that, in most of the cases, the antifungal activities against the Candida strains correlate well with the energy of the HOMO orbital, suggesting that an external electrophilic attack to these compounds or an electron donation from these compounds to the targets might be involved in their biochemical pathways. On the other hand, for the Aspergillus and Penicillium strains the antifungal activities of the compounds under study correlate well with log P. Hence, their ability to transpose biological membranes might be responsible for their capacity to reach the target. Taking into consideration the reported resistance to the current antifungal drugs and their adverse side effects, the compounds under study deserve to be further investigated as antimicrobial drug candidates.

In this paper, density functional theory calculations of nuclear magnetic resonance (NMR) chemical shifts for l-quebrachitol isomer, previously studied in our group, are reported with the aim of investigating in more detail the water solvent effect on the prediction of 1H NMR spectra. In order to include explicit water molecules, 20 water-l-quebrachitol configurations obtained from Monte Carlo simulation were selected to perform geometry optimizations using the effective fragment potential method encompassing 60 water molecules around the solute. The solvated solute optimized geometries were then used in B3LYP/6-311+G(2d,p) NMR calculations with PCM-water. The inclusion of explicit solvent in the B3LYP NMR calculations resulted in large changes in the 1H NMR profiles. We found a remarkable improvement in the agreement with experimental NMR profiles when the explicit hydrated l-quebrachitol structure is used in B3LYP 1H NMR calculations, yielding a mean absolute error (MAE) of only 0.07 ppm, much lower tha...

The redox chemistry of H

The redox chemistry of H2S with NO and other oxidants containing the NO group is discussed on a mechanistic basis because of the expanding interest in their biological relevance, with an eye open to the chemical differences of H2S and thiols RSH. We focus on the properties of two "crosstalk" intermediates, SNO- (thionitrite) and SSNO- (perthionitrite, nitrosodisulfide) based in the largely controversial status on their identity and chemistry in aqueous/nonaqueous media, en route to the final products N2O, NO2 -, NH2OH/NH3, and S8. Thionitrous acid, generated either in the direct reaction of NO + H2S or through the transnitrosation of RSNO's (nitrosothiols) with H2S at pH 7.4, is best described as a mixture of rapidly interconverting isomers, {(H)SNO}. It is reactive in different competitive modes, with a half-life of a few seconds at pH 7.4 for homolytic cleavage of the N-S bond, and could be deprotonated at pH values of up to ca. 10, giving SNO-, a less reactive species than {(H)SNO}. The latter mixture can also react with HS-, giving HNO and HS2 - (hydrogen disulfide), a S0(sulfane)-transfer reagent toward {(H)SNO}, leading to SSNO-, a moderately stable species that slowly decomposes in aqueous sulfide-containing solutions in the minute-hour time scale, depending on [O2]. The previous characterization of HSNO/SNO- and SSNO- is critically discussed based on the available chemical and spectroscopic evidence (mass spectrometry, UV-vis, 15N NMR, Fourier transform infrared), together with computational studies including quantum mechanics/molecular mechanics molecular dynamics simulations that provide a structural and UV-vis description of the solvatochromic properties of cis-SSNO- acting as an electron donor in water, alcohols, and aprotic acceptor solvents. In this way, SSNO- is confirmed as the elusive "yellow intermediate" (I412) emerging in the aqueous crosstalk reactions, in contrast with its assignment to polysulfides, HSn -. The analysis extends to the coordination abilities of {(H)SNO}, SNO-, and SSNO- into heme and nonheme iron centers, providing a basis for best unraveling their putative specific signaling roles. Fil: Marcolongo, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Venâncio, Mateus F.. Universidade Federal de Minas Gerais; Brasil Fil: Rocha, Willian R.. Universidade Federal de Minas Gerais; Brasil Fil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Olabe Iparraguirre, Jose Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina

In this article density functional theory (DFT)-based calculations were employed to investigate the electrochemistry of the antitumor ruthenium complexes trans-tetrachloro(dimethylsulfoxide)imidazole ruthenate(III) (NAMI-A) and trans-[tetrachlorobis(1.-indazole)ruthenate(III)] (KP1019), their hydrolysis products as well as their interactions with biological S-donors and N-donors targets as cysteine, glutathione and guanine nucleobase. The compounds exhibit different electrochemical behavior upon hydrolysis. While the reduction potential of NAMI-A increases up to 0.8 V upon hydrolysis, the reduction potential of KP1019 remains almost constant after the first hydrolysis. NAMI-A and KP1019 complexes have thermodynamic preference to be reduced prior to undergoing hydrolysis and, strong preference to undergo successive hydrolysis instead of interacting with the S-donor and N-donor ligands. Interaction with S-donor ligands in the unprotonated form is highly unfavorable, with the free energy in solution (ΔGsol) ≥ 18 kcal mol-1. For both complexes, the interaction with the guanine and glutathione are of the same magnitude (ΔGsol ca. –0.6 kcal mol-1) meaning that these ligands can compete for binding to the metallodrug.

In this article, density functional theory in conjunction with Monte Carlo statistical mechanical simulation was used to investigate the electronic structure, reduction potential, solvation, and solvent effects on the electronic spectra of nitrosyl ammine complexes using [Ru(NH3)5(NO)]2+/3+ as model compounds. In addition, ligand exchange reactions with solvent water molecules were also investigated. It is shown that the complexes are involved in strong hydrogen bonds in aqueous solution, with mean average energies of −13.5 ± 0.4 and −22.4 ± 0.4 kcal mol–1 for Ru(II) and Ru(III), respectively. Interestingly, for all the complexes studied, the NO ligand is not involved in hydrogen bonding interactions in aqueous solution. These strong hydrogen bonds are responsible for the high stability of these complexes in aqueous solution, showing formation constants Kf greater than 1021. The complex [Ru(NH3)5(NO)]3+ can easily be reduced by biological reducing agents in both the singlet and triplet states; however, th...

Complexes [Bi(2AcPh)Cl2]·0.5H2O (1), [Bi(2AcpClPh)Cl2] (2), [Bi(2AcpNO2Ph)Cl2] (3), [Bi(2AcpOHPh)Cl2]·2H2O (4), [Bi(H2BzPh)Cl3]·2H2O (5), [Bi(H2BzpClPh)Cl3] (6), [Bi(2BzpNO2Ph)Cl2]·2H2O (7) and [Bi(H2BzpOHPh)Cl3]·2H2O (8) were obtained with 2-acetylpyridine phenylhydrazone (H2AcPh), its -para-chloro-phenyl- (H2AcpClPh), -para-nitro-phenyl (H2AcpNO2Ph) and -para-hydroxy-phenyl (H2AcpOHPh) derivatives, as well as with the 2-benzoylpyridine phenylhydrazone analogues (H2BzPh, H2BzpClPh, H2BzpNO2Ph, H2BzpOHPh). Upon coordination to bismuth(III) antibacterial activity against Gram-positive and Gram-negative bacterial strains significantly improved except for complex (4). The cytotoxic effects of the compounds under study were evaluated on HL-60, Jurkat and THP-1 leukemia, and on MCF-7 and HCT-116 solid tumor cells, as well as on non-malignant Vero cells. In general, 2-acetylpyridine-derived hydrazones proved to be more potent and more selective as cytotoxic agents than the corresponding 2-benzoylpyridine-derived counterparts. Exposure of HCT-116 cells to H2AcpClPh, H2AcpNO2Ph and complex (3) led to 99% decrease of the clonogenic survival. The IC50 values of these compounds were three-fold smaller when cells were cultured in soft-agar (3D) than when cells were cultured in monolayer (2D), suggesting that they constitute interesting scaffolds, which should be considered in further studies aiming to develop new drug candidates for the treatment of colon cancer.

In this article, we investigated the hydroxylation of methane catalyzed by the binuclear copper site of pMMO enzyme, through a radical rebound mechanism. All intermediates and transition states along the reaction coordinate were located and the energies involved in the mechanism calculated using the B3LYP functional including dispersion effects. Our B3LYP-D2 results show that the singlet state of (µ-1,2-peroxo)Cu(II)2 complex plays an important role as the lowest energy species prior to C-H bond activation. A crossing between the singlet and triplet PES is suggested to occur before the cleavage of C-H bond of methane, where the triplet (bis-µ-oxo)Cu(III)2 is very reactive towards activation of the strong C-H bond of methane. The C-H bond activation is the rate-determining step of the reaction, with an activation energy of 18.6 kcal mol-1 relative to the singlet (µ-1,2-peroxo)Cu(II)2 species. Comparison with previous theoretical results for a non-synchronous concerted mechanism suggests the radical rebound mechanism as a possible alternative pathway. crosscheck: This document is CrossCheck deposited related_data: Supplementary Information identifier: Willian R. Rocha (ResearcherID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0) history: Received 12 July 2015; Accepted 28 October 2015; Accepted Manuscript published 30 October 2015; Advance Article published 24 December 2015; Version of Record published 2 February 2016 ispartof: Dalton Transactions vol:45 issue:6 pages:2492-2504 ispartof: location:England status: published

In the present work, density functional theory (DFT) calculations at the B3LYP/6-31+G(d) and including dispersion effects were used to investigate the hydrolysis of paraoxon, using a cluster model of the active site of Cd

In this work, the complexation of the hazardous β-lactamic antibiotic amoxicillin (AMX) with Fe3+ ions during coagulation was investigated. New bands in the ultraviolet-visible (UV-vis) spe...

In this work the neutral or spontaneous hydrolysis of paraoxon, one of the most popular organophosphate pesticides, in aqueous solution was investigated at the DFT and MP2 levels of theory, using a combination of local solvation of the phosphoryl group with explicit water molecules, and treating the long range solvent effects using continuum solvation model. In contrast to the alkaline hydrolysis, the neutral hydrolysis takes place in two steps, through an AN + DN mechanism, with formation of a pentacoordinate phosphorane intermediate. The reaction has activation free energies of 31.8 and 1.9 kcal mol−1 for the first and second steps, respectively, and has an overall reaction free energy of −9.3 kcal mol−1, computed at the MP2/6–311++G(2d,2p)//B3LYP/6–31+G(d) level of theory. The reaction proceeds through a sequence of proton transfer processes from the attacking water molecule and ends with the protonation of the nitrophenolate leaving group. Explicit description of the local solvating water molecules is essential to describe the proton transfer processes along the reaction coordinate and to stabilize the pentacoordinate intermediate formed. The neutral hydrolysis is very slow and has an overall rate constant of 3.05 × 10−11 s−1, computed at the MP2/6–311++G(2d,2p)//B3LYP/6–31+G(d) level of theory. This result, in conjunction with the sensitivity of the rate constant to the experimental conditions, indicates that the hydrolysis of paraoxon in aqueous solution can be even slower than predicted experimentally.

Ab initio molecular dynamics simulations were used to investigate the early chemical events involved in the dynamics of nitric oxide (NO ), nitrosonium cation (NO + ) and nitroxide anion (NO − ) in aqueous solution. The NO + ion is very reactive in aqueous solution having a lifetime of ∼4 × 10 −13 s, which is shorter than the value of 3 × 10 −10 s predicted experimentally. The NO + reacts generating the nitrous acid as an intermediate and the NO 2 − ion as the final product. The dynamics of NO revealed the reversibly formation of a transient anion radical species HONO − .

In this work DFT and CCSD(T) calculations were carried out to study the structure, energetic of the interactions, IR, UV/Vis spectra and the nature of the interactions related to Metal–fluoroalkane complexes of the type M(CO) 5 (CH 3 F) [M = Cr, Mo and W]. All possible coordination modes of the CH 3 F molecule to the metallic fragments were attempted, however, only the η 1 mode through the hydrogen or fluorine atoms is obtained. The computed DFT vibrational frequencies showed that upon coordination the ν(C–H) asym and ν(C–F) asym modes have pronounced red shifts compared with the free fluoroalkane, and thus may be an important way to characterize and follow the alkane/fluoroalkane coordination to the metallic fragment. TD-DFT calculations of the electronic transitions show that, compared with the free metallic fragments, CH 3 F coordination affects drastically the MLCT band, showing a maximum blue shift of 201 nm for the [W(CO) 5 (CH 3 F)]–η 1 F complex. Comparison with CCSD(T) energies shows that the B3LYP-D2 and BP86-D2 methods provide an accurate description of the energetic involved in metal–fluoroalkane complexes investigated.

Steady-state and time-resolved spectroscopy and quantum chemical computational studies were employed to investigate ground and excited state proton transfer of a novel series of ortho-(1H-imidazol-2-yl)naphthol constitutional isomers: 1-(1H-imidazol-2-yl)naphthalen-2-ol (1NI2OH), 2-(1H-imidazol-2-yl)naphthalen-1-ol (2NI1OH) and 3-(1H-imidazol-2-yl)naphthalen-2-ol (3NI2OH). Proper Near Attack Conformations (NACs) involving a strong intramolecular hydrogen bond between the naphthol moiety and the ortho-imidazole group account for the highest ground state acidity of 2NI1OH compared with 1NI2OH and 3NI2OH. Moreover, ESIPT for 2NI1OH and 3NI2OH is further associated with planar chelate H-ring formation whereas 1NI2OH shows the highest ESIPT barrier and a noncoplanar imidazole group. In addition to energetic and structural requirements, the final state also depends on electronic configuration of the ESIPT product with the neutral 3NI2OH showing an ICT effect that correlates with the excited state pKa of the cationic species.

Azanone (nitroxyl, HNO) is a highly reactive compound whose biological role is still a matter of debate. One possible route for its formation is NO reduction by biological reductants. These reactions have been historically discarded due to the negative redox potential for the NO,H+/HNO couple. However, the NO to HNO conversion mediated by vitamins C, E, and aromatic alcohols has been recently shown to be feasible from a chemical standpoint. Based on these precedents, we decided to study the reaction of NO with thiols as potential sources of HNO. Using two complementary approaches, trapping by a Mn porphyrin and an HNO electrochemical sensor, we found that under anaerobic conditions aliphatic and aromatic thiols (as well as selenols) are able to convert NO to HNO, albeit at different rates. Further mechanistic analysis using ab initio methods shows that the reaction between NO and the thiol produces a free radical adduct RSNOH•, which reacts with a second NO molecule to produce HNO and a nitrosothiol. The nitrosothiol intermediate reacts further with RSH to produce a second molecule of HNO and RSSR, as previously reported. Fil: Suarez, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Muñoz, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Álvarez, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Venâncio, Mateus F.. Universidade Federal de Minas Gerais; Brasil Fil: Rocha, Willian R.. Universidade Federal de Minas Gerais; Brasil Fil: Bikiel, Damian Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina

In this work, quantum mechanical calculations and Monte Carlo statistical mechanical simulations were carried out to investigate the solvation properties of HNO in aqueous solution and to evaluate the proton-coupled one electron reduction potential of 2NO to 1HNO, which is essential missing information to understand the fate of 2NO in the biological medium. Our results showed that the 1HNO molecule acts mainly as a hydrogen bond donor in aqueous solution with an average energy of -5.5 ± 1.3 kcal/mol. The solvation free energy of 1HNO in aqueous solution, computed using three approaches based on the linear response theory, revealed that the current prediction of the hydration free energy of HNO is, at least, 2 times underestimated. We proposed two pathways for the production of HNO through reduction of NO. The first pathway is the direct reduction of NO through proton-coupled electron transfer to produce HNO, and the second path is the reduction of the radical anion HONO•-, which is involved in equilibrium with NO in aqueous solution. We have shown that both pathways are viable processes under physiological conditions, having reduction potentials of E°′ = -0.161 V and E°′ ≈ 1 V for the first and second pathways, respectively. The results shows that both processes can be promoted by well-known biological reductants such as NADH, ascorbate, vitamin E (tocopherol), cysteine, and glutathione, for which the reduction potential at physiological pH is around -0.3 to -0.5 V. The computed reduction potential of NO through the radical anion HONO•- can also explain the recent experimental findings on the formation of HNO through the reduction of NO, promoted by H2S, vitamin C, and aromatic alcohols. Therefore, these results contribute to shed some light into the question of whether and how HNO is produced in vivo and also for the understanding of the biochemical and physiological effects of NO. Fil: Venâncio, Mateus F.. Universidade Federal de Minas Gerais; Brasil Fil: Doctorovich, Fabio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Rocha, Willian R.. Universidade Federal de Minas Gerais; Brasil

In this work, quantum mechanical calculations and Monte Carlo statistical mechanical simulations were carried out to investigate the solvation properties of HNO in aqueous solution and to evaluate the proton-coupled one electron reduction potential of

In this paper, density functional theory calculations of nuclear magnetic resonance (NMR) chemical shifts for l-quebrachitol isomer, previously studied in our group, are reported with the aim of investigating in more detail the water solvent effect on the prediction of

In this work the solvent effects on the structure and metal-to-ligand charge transfer (MLCT) transition of the complex [Ru(NH3)5(Pyrazine)]2+ was investigated in aqueous solution, using the hybrid Density Functional Theory/Effective Fragment Potential Hamiltonian (DFT/EFP/MD) approach. The MLCT transition causes a large charge separation in the complex and produces a dipole moment variation of 8.3 ± 1.1 Debye upon excitation in solution and causes a large red-shift of 0.55 ± 0.15 eV. The solvatochromic shift can be attributed to the large charge separation accompanying the MLCT transition in solution.

The two novel dithiocarbamate salts, [Na{S2CNR(R1)}] (i), [Na{S2CNR(R2)}] (ii), R = methyl, R1 = CH2CH(OMe)2, R2 = 2-methyl-1,3-dioxolane, previously synthesized by us, have been used in chemical reactions with triorganotin halides. Hence, five new complexes: [SnPh3{S2CNR(R1)}] (1), [SnCy3{S2CNR(R1)}] (2), [SnMe3{S2CNR(R2)}] (3), [SnPh3{S2CNR(R2)}] (4) and [SnCy3{S2CNR(R2)}] (5), [R = methyl, R1 = CH2CH(OMe)2, and R2 = 2-methyl-1,3-dioxolane], have been isolated. All compounds were authenticated in terms of infrared, 1H and 13C NMR, and the complexes were also characterized using 119Sn NMR, 119Sn Mossbauer and X-ray crystallography, in the case of complexes (1), (4) and (5). The biological activity of all derivatives has been screened in terms of IC90 (μmol L−1) and IC50 (μmol L−1) against Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus and Penicillium citrinum, and the results correlated well with a performed study of structure–activity relationship (SAR). Complexes (1) and (4) displayed nanomolar inhibition concentration in terms of IC50.

We report a study of the P–O bond cleavage of the anion of 2,4-dinitrophenyl ethyl phosphate (2,4-DNPEP), promoted by methylamine. The aminolysis reaction was investigated in the gas phase and an aqueous environment using the hybrid quantum mechanical/effective fragment potential (QM/EFP) approach. According to the B3LYP/6-31++G(d,p) results, in the gas phase the cleavage of the P–O bond of 2,4-DNPEP proceeds in one step through a concerted mechanism, with an activation free energy of 39 kcal/mol. Including solvent effects at the B3LYP/6-31++G(d,p)/EFP level changes the reaction to a two-step associative mechanism. The first step corresponds to the formation of the P–NHMe bond and the second step to concerted proton transfer and P–O(2,4-dinitrophenolate) cleavage. In the absence of any assistance of water molecules to promote the proton transfer, the second step is rate determining with an activation free energy for the breakdown of the intermediate of 21.8 kcal/mol at the MP2/cc-pVTZ level and a free energy of activation of 32.3 kcal/mol for the overall reaction. However, the proton transfer with the assistance of a water molecule may occur without significant energy barrier. The results show how solvent can play an important role in favoring an associative mechanism for the aminolysis of phosphate diesters, through the formation and stabilization of a pentacoordinate phosphorane intermediate.

Spray dried cross-linked chitosan/cobalt ferrite composite was synthesized and applied as an adsorbent for the removal of acid orange II and methylene blue. The composite was structurally, thermally, morphologically and magnetically characterized. The result obtained shows that the magnetic composite was in form of microspheres, while cobalt ferrite was encapsulated in the cross-linked chitosan with saturation magnetization of 10.79 emu g -1 . Adsorption studies revealed that acid orange II adsorbed more favorably on the composite than methylene blue. The adsorption process is spontaneous and exothermic. Liu isotherm model was found to be applicable for the adsorption process. Computational studies showed that the formation of hydrogen bond between acid orange II and the magnetic composite (at both acidic and alkaline pH) contributed to its better adsorption than methylene blue. Adsorption capacity of acid orange II at pH 3 and methylene blue at pH 12 are 542 and 173 mg g -1 respectively at 303 K base on Liu isotherm model.

Aiming at understanding the effect of the replacement of iron by ruthenium in the Protoporphyrin IX (PPIX) system of the heme group, in this work density functional theory calculations were performed to investigate the structures, nature of the M–NO bond and electronic spectra of the complexes [ M (Im)(PPIX)( L )] q , where M = Fe 2+ and Ru 2+ , Im = Imidazole ring, PPIX = Protoporphyrin IX of the heme group and L = NO + , NO and NO − . Energetic and structural results obtained at the B3LYP/SBKJC/6-31G(d) level of theory indicates that the NO coordinates preferentially through the nitrogen atom and its oxidized form NO + produces more stable complexes. Charge and energy decomposition analysis revealed that, independent of the coordination mode, the interaction of NO species with the ruthenium fragment is stronger than with iron. TD-DFT calculations predict that the transition that can lead to photodissociation of the Ru–NO bond occurs at 419 nm and if the NO coordinates to ruthenium in its oxidized form this transition is blue-shifted to 384 nm. The results obtained in this work also gives support to conclude that ruthenium complexes with the protoporphyrin IX (PPIX) system can strongly bind NO, which can be used to capture NO species, and releasing it upon irradiation with visible light.

Complexes [In(2Ac4oClPh)Cl2(MeOH)] (1), [In(2Ac4pFPh)Cl2(MeOH)] (2), [In(2Ac4pClPh)Cl2(MeOH)] (3) and [In(2Ac4pIPh)Cl2(MeOH)] (4) were obtained with N(4)-ortho-chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4oClPh), N(4)-para-fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4pFPh), N(4)-para-chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4pClPh) and N(4)-para-iodophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4pIPh). Theoretical studies suggested that the coordinated methanol molecule can be easily replaced by DMSO used in the preparation of stock solutions, with the formation of [In(L)Cl2(DMSO)] (HL = thiosemicarbazonate ligand), and that the replacement of DMSO by water is unfavorable. However, for all complexes the displacement of one or two chloride ligands by water in aqueous solution is extremely favorable. The cytotoxic activity of the compounds was evaluated against HL-60, Jurkat and THP-1 leukemia and against MDA-MB-231 and HCT-116 solid tumor cell lines, as well as against Vero non-malignant cells. The cytotoxicity and selectivity indexes (SI) increased in several cases for the indium(III) complexes in comparison with the free thiosemicarbazones. The antimicrobial activity of the compounds was investigated against Candida albicans, Candida dubliniensis, Candida lusitaniae and Candida parapsilosis. In many cases complexation resulted in a substantial increase of the antifungal activity. Complexes (1–4) were revealed to be very active against C. lusitaniae and C. dubliniensis. Structure–activity relationship (SAR) studies were carried out to identify the physico-chemical properties that might be involved in the antifungal action, as well as in the cytotoxic effect of the compounds against HL-60 cells. In both cases, correlations between the bioactivity and physico-chemical properties did not appreciably change when the chloride ligands in [In(L)Cl2(DMSO)] were replaced by water molecules, suggesting [In(L)Cl(H2O)(DMSO)]+ or [In(L)(H2O)2(DMSO)]2+ to be the species that interact with the biological media.