5-Amino-1,2,4-triazol-3-one Degradation by Indirect Photolysis: A Density Functional Theory Study.

Sunlight irradiation induces formation of reactive oxygen species (superoxide, hydroperoxyl radical, singlet oxygen, etc.), which readily take part in degradation of environmental pollutants. Being a primary ingredient in a suite of insensitive munition formulations, NTO (5-nitro-1,2,4-triazol-3-one) can be released onto training range soils and reduced to ATO (5-amino-1,2,4-triazol-3-one) by soil bacteria or iron-contained minerals. ATO can be dissolved in surface water and groundwater due to its good water solubility and then undergo further decomposition. A detailed investigation of possible mechanisms for ATO decomposition in water induced by superoxide, hydroperoxyl radical, and singlet oxygen as pathways for ATO environmental degradation was performed by computational study at the PCM(Pauling)/M06-2X/6-311++G(d,p) level. Hydrolysis and degradation of ATO induced by superoxide are unlikely to occur due to the high activation energy or endergonicity of the processes. The hydroperoxyl radical causes rapid and reversible hydrogen transfer from ATO, while an attachment of the hydroperoxyl radical to ATO can induce decomposition of ATO, leading to its mineralization. Singlet oxygen shows a higher reactivity toward ATO than the hydroperoxyl radical. Decomposition of ATO was found to be a multistep process that begins with singlet oxygen attachment to the carbon atom of the C═N double bond. The intermediate that is formed undergoes recyclization, cycle opening, and sequential elimination of nitrogen gas, ammonia, and carbon(IV) oxide. Isocyanic acid, which arises intermediately, hydrolyzes into ammonia and carbon(IV) oxide. Calculated activation energies and high exergonicity of the studied processes support the contribution of singlet oxygen and the hydroperoxyl radical to ATO degradation into low-weight inorganic compounds in the environment.

Degradation of NTO induced by superoxide and hydroperoxyl radicals: a comprehensive DFT study.

Reactive oxygen species, produced in the aquatic environment under sunlight irradiation, actively take part in degradation of environmental pollutants. NTO (5-nitro-1,2,4-triazol-3-one), being a primary ingredient in a suite of insensitive munitions formulations, may be released into training range soils after incomplete detonations and dissolved in surface water and groundwater due to good water solubility. A detailed investigation of a possible mechanism for NTO decomposition in water induced by superoxide and hydroperoxyl radicals as one of the pathways for NTO environmental degradation was performed with a computational study at the PCM(Pauling)/M06-2X/6-311++G(d,p) level. Superoxide causes rapid deprotonation of NTO. Decomposition of NTO induced by hydroperoxyl radicals was found to be a multistep process leading to mineralization of the nitrocompound. The reaction process may begin with hydroperoxyl radical attachment to carbon atom of the CN double bond of NTO, then proceeds through rupture of C-N bonds and addition of water molecules leading to the formation of nitrous acid, ammonia, nitrogen gas, hydrazine, and carbon(IV) oxide. The obtained results indicate that the anionic form of NTO shows a higher reactivity towards hydroperoxyl radicals than its neutral form. Excitation of NTO by sunlight enables complete mineralization of NTO induced by superoxide. The calculated activation energies and exergonicity of the studied processes support the contribution of hydroperoxyl radicals and superoxide to the degradation of NTO in the environment into low-weight inorganic compounds.

Role of Molecular Singlet Oxygen in Photochemical Degradation of NTO: DFT Study.

NTO (5-nitro-1,2,4-triazol-3-one), an energetic material used in military applications, may be released to the environment and dissolved in surface water and groundwater due to its good water solubility. Singlet oxygen is an important reactive oxygen species produced in the aquatic environment under sunlight irradiation. A detailed investigation of the possible mechanism for NTO decomposition in water induced by singlet oxygen as one of the pathways for NTO environmental degradation was performed by a computational study at PCM(Pauling)/M06-2X/6-311++G(d,p) level. Decomposition of NTO was found to be a multistep process that may begin with singlet oxygen attachment to the carbon atom of the C═N double bond. The formed intermediate undergoes cycle opening, and nitrogen gas, nitrous acid, and carbon (IV) oxide elimination. Isocyanic acid, arisen transiently, hydrolyzes into ammonia and carbon (IV) oxide. The obtained results show a significant increase in reactivity of the anionic form of NTO as compared to its neutral form. The calculated activation energies and high exothermicity of the studied processes support the contribution of singlet oxygen to NTO degradation into low-weight inorganic compounds in the environment.

Role of Hydroxyl Radical in Degradation of NTO: DFT Study.

Hydroxyl radicals are important reactive oxygen species produced in the aquatic environment under sunlight irradiation. Many organic pollutants may be decomposed as they encounter hydroxyl radicals, due to their high oxidative ability. NTO (5-nitro-1,2,4-triazol-3-one), an energetic material used in military applications, may be released to the environment and dissolved in surface water and groundwater due to its good water solubility. A detailed investigation of the possible mechanism for NTO decomposition in water induced by hydroxyl radical as one of the pathways for NTO environmental degradation was performed by computational study at the PCM/M06-2X/6-311++G(d,p) level. Decomposition of NTO was found to be a multistep process that may begin with an addition of hydroxyl radical to the carbon atom of C═N double bond and consequent release of a nitrite radical. The formed intermediate undergoes a series of chemical transformations that include the attachments of hydroxyl radical to carbon atoms, the transfer of hydrogen to hydroxyl radical, isomerization, and bond cleavage, leading to low-weight inorganic compounds, such as ammonia, nitrogen gas, nitrous acid, nitric acid, and carbon(IV) oxide. The anionic form of NTO is more reactive toward interaction with the hydroxyl radical as compared with its neutral form. Calculated activation energies and high exergonicity of the studied process support the significant contribution of the hydroxyl radical to NTO mineralization in environment.

Role of Singlet Oxygen in the Degradation of Selected Insensitive Munitions Compounds: A Comprehensive, Quantum Chemical Investigation.

DNAN (2,4-dinitroanisole), NTO (3-nitro-1,2,4-triazol-5-one), and NQ (nitroguanidine) are important energetic materials used in military applications. They may find their way to the environment during manufacturing, transportation, storage, training, and disposal. A detailed investigation of possible mechanisms for reactions of the nitrocompounds with singlet oxygen, one of the potential methods for their degradation, was performed by computational study using the PCM(Pauling)/M06-2X/6-311++G(d,p) approach. Obtained results suggest that reactivity of the investigated munitions compounds toward singlet oxygen follows the order: DNAN > NTO(anion) > NQ ≫ NTO. DNAN is involved in [4 + 2]-addition with oxygen, and further formation of diepoxide or epoxyketone through diradical intermediates have been predicted. The NTO may undergo intramolecular rearrangement with formation of peroxide compound or nitrite radical elimination, and NQ may be transformed into urea.

Structure and electrochemical properties for complexes of nitrocompounds with inorganic ions: A theoretical approach.

Reduction and oxidation (redox) reactions are widely used for removal of nitrocompounds from contaminated soil and water. Structures and redox properties for complexes of nitrocompounds, such as 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), 2,4-dinitroanisole (DNAN), and 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO), with common inorganic ions (Na(+) , Cl(-) , NO3-) were investigated at the SMD(Pauling)/PCM(Pauling)/MPWB1K/TZVP level of theory. Atoms in molecules (AIM) theory was applied to analyze the topological properties of the bond critical points involved in the interactions between the nitrocompounds and the ions. Topological analyses show that intermolecular interactions of the types O(N)…Na(+) , C-H…Cl(-) ( ONO2-), and C…Cl(-) ( ONO2-) may be discussed as noncovalent closed-shell interactions, while N-H···Cl(-) ( ONO2-) hydrogen bonds are partially covalent in nature. Complexation causes significant decrease of redox activity of the nitrocompounds. Analysis of the reduction potentials of the complexes obtained through application of the Pourbaix diagram of an iron/water system revealed that sodium complexes of NTO might be reduced by metallic iron. © 2016 Wiley Periodicals, Inc.

Novel enhanced applications of QSPR models: Temperature dependence of aqueous solubility.

A model developed to predict aqueous solubility at different temperatures has been proposed based on quantitative structure-property relationships (QSPR) methodology. The prediction consists of two steps. The first one predicts the value of k parameter in the linear equation lgSw=kT+c, where Sw is the value of solubility and T is the value of temperature. The second step uses Random Forest technique to create high-efficiency QSPR model. The performance of the model is assessed using cross-validation and external test set prediction. Predictive capacity of developed model is compared with COSMO-RS approximation, which has quantum chemical and thermodynamic foundations. The comparison shows slightly better prediction ability for the QSPR model presented in this publication. © 2016 Wiley Periodicals, Inc.

In Silico Alkaline Hydrolysis of Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine: Density Functional Theory Investigation.

HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), an energetic material used in military applications, may be released to the environment during manufacturing, transportation, storage, training, and disposal. A detailed investigation of a possible mechanism of alkaline hydrolysis, as one of the most promising methods for HMX remediation, was performed by computational study at PCM(Pauling)/M06-2X/6-311++G(d,p) level. Obtained results suggest that HMX hydrolysis at pH 10 represents a highly exothermic multistep process involving initial deprotonation and nitrite elimination, hydroxide attachment accompanied by cycle cleavage, and further decomposition of cycle-opened intermediate to the products caused by a series of C-N bond ruptures, hydroxide attachments, and proton transfers. Computationally predicted products of HMX hydrolysis such as nitrite, 4-nitro-2,4-diazabutanal, formaldehyde, nitrous oxide, formate, and ammonia correspond to experimentally observed species. Based on computed reaction pathways for HMX decomposition by alkaline hydrolysis, the kinetics of the entire process was modeled. Very low efficiency of this reaction at pH 10 was observed. Computations predict significant increases (orders of magnitude) of the hydrolysis rate for hydrolysis reactions undertaken at pH 11, 12, and 13.

Are the reduction and oxidation properties of nitrocompounds dissolved in water different from those produced when adsorbed on a silica surface? A DFT M05-2X computational study.

The reduction and oxidation properties of four nitrocompounds (trinitrotoluene [TNT], 2,4-dinitrotoluene, 2,4-dinitroanisole, and 5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one [NTO]) dissolved in water as compared with the same properties for compounds adsorbed on a silica surface were studied. To consider the influence of adsorption, cluster models were developed at the M05/tzvp level. A hydroxylated silica (001) surface was chosen to represent a key component of soil. The PCM(Pauling) and SMD solvation models were used to model water bulk influence. The following properties were analyzed: electron affinity, ionization potential, reduction Gibbs free energy, oxidation Gibbs free energy, and reduction and oxidation potentials. It was found that adsorption and solvation decrease gas phase electron affinity, ionization potential, and Gibbs free energy of reduction and oxidation, and thus, promote redox transformation of nitrocompounds. However, in case of solvation, the changes are more significant than for adsorption. This means that nitrocompounds dissolved in water are easier to transform by reduction or oxidation than adsorbed ones. Among the considered compounds, TNT was found to be the most reactive in an electron attachment process and the least reactive for an electron detachment transformation. During ionization, a deprotonation of adsorbed NTO was found to occur.

Structure and Redox Properties of 5-Amino-3-nitro-1H-1,2,4-triazole (ANTA) Adsorbed on a Silica Surface: A DFT M05 Computational Study.

A cluster approximation was applied at the M05/tzvp level to model an adsorption of 5-amino-3-nitro-1H-1,2,4-triazole (ANTA) on the (001) surface of α-quartz. Structures of the obtained ANTA-silica complexes confirm a nearly parallel orientation of the nitro compound toward the surface. The atoms in molecules (AIM) method was applied to analyze binding between ANTA and the silica surface. Attachment or loss of an electron was found to lead to a significant deviation from coplanarity in the complexes and to a strengthening of a hydrogen bonding. Redox properties of the adsorbed ANTA were compared with those of gas-phase and hydrated species by calculation of the ionization potential, electron affinity, oxidation and reduction Gibbs free energies, and oxidation and reduction potentials. It was shown that the adsorbed ANTA has a lower ability to undergo redox transformations as compared to that of the hydrated one.

In silico kinetics and mechanism of interaction of cis-2-butene-1,4-dial with 2'-deoxycytidine.

Newly proposed approach involving computational analysis of multistep chemical reactions has been successfully applied to study the interaction between 2'-deoxycytidine and cis-2-butene-1,4-dial, a metabolite of furan. The new method comprises a combination of few steps. They include the prediction of the reaction mechanism, calculation of Gibbs free energies for the reaction pathway, and conversion of barrier energies to rate constants. On the basis of the results of previous steps, corresponding kinetic equations are constructed and solved. Such a procedure allows one to indicate the definite concentration of reaction species (reactants, intermediates, and products) at any moment in time. Obtained results show that 2'-deoxycytidine reacts with cis-2-butene-1,4-dial to form primary products, which are represented by four polycyclic diastereomers. These primary products further transform to more stable secondary product by dehydration, which is catalyzed by acid. The obtained data demonstrate that cis-2-butene-1,4-dial plays a key role in furan-induced carcinogenesis.

Comprehensive investigations of kinetics of alkaline hydrolysis of TNT (2,4,6-trinitrotoluene), DNT (2,4-dinitrotoluene), and DNAN (2,4-dinitroanisole).

Combined experimental and computational techniques were used to analyze multistep chemical reactions in the alkaline hydrolysis of three nitroaromatic compounds: 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), and 2,4-dinitroanisole (DNAN). The study reveals common features and differences in the kinetic behavior of these compounds. The analysis of the predicted pathways includes modeling of the reactions, along with simulation of UV-vis spectra, experimental monitoring of reactions using LC/MS techniques, development of the kinetic model by designing and solving the system of differential equations, and obtaining computationally predicted kinetics for decay and accumulation of reactants and products. Obtained results suggest that DNT and DNAN are more resistant to alkaline hydrolysis than TNT. The direct substitution of a nitro group by a hydroxide represents the most favorable pathway for all considered compounds. The formation of Meisenheimer complexes leads to the kinetic first-step intermediates in the hydrolysis of TNT. Janovsky complexes can also be formed during hydrolysis of TNT and DNT but in small quantities. Methyl group abstraction is one of the suggested pathways of DNAN transformation during alkaline hydrolysis.

Environmental impact of PFAS: Filling data gaps using theoretical quantum chemistry and QSPR modeling.

Per- and polyfluorinated alkyl substances (PFAS), known for their widespread environmental presence and slow degradation, pose significant concerns. Of the approximately 10,000 known PFAS, only a few have undergone comprehensive testing, resulting in limited experimental data. In this study, we employed a combination of physics-based methods and data-driven models to address gaps in PFAS bioaccumulation potential. Using the COnductor-like Screening MOdel for Realistic Solvents (COSMO-RS) method, we predicted n-octanol/water partition coefficients (logKOW), crucial for PFAS bioaccumulation. Our developed Quantitative Structure-Property Relationship (QSPR) model exhibited high accuracy (R2 = 0.95, RMSEC = 0.75) and strong predictive ability (Q2LOO = 0.93, RMSECV = 0.83). Leveraging the extensive NORMAN, we predicted logKOW for over 4,000 compounds, identifying 244 outliers out of 4519. Further categorizing the database into eight Organisation for Economic Co-operation and Development (OECD) categories, we confirmed fluorine atoms role in enhanced bioaccumulation. Utilizing predicted logKOW, water solubility logSW, and vapor pressure logVP values, we calculated additional physicochemical properties that are responsible for the transport and dispersion of PFAS in the environment. Parameters such as Henry's Law (kH), air-water partition coefficient (KAW), octanol-air coefficient (KOA), and soil adsorption coefficient (KOC) exhibited favorable correlations with literature data (R2 > 0.66). Our study successfully filled data gaps, contributing to the understanding of ubiquitous PFAS in the environment and estimating missing physicochemical data for these compounds.

From RNA sequence to its three-dimensional structure: geometrical structure, stability and dynamics of selected fragments of SARS-CoV-2 RNA.

In this computational study, we explore the folding of a particular sequence using various computational tools to produce two-dimensional structures, which are then transformed into three-dimensional structures. We then study the geometry, energetics and dynamics of these structures using full electron quantum-chemical and classical molecular dynamics calculations. Our study focuses on the SARS-CoV-2 RNA fragment GGaGGaGGuguugcaGG and its various structures, including a G-quadruplex and five different hairpins. We examine the impact of two types of counterions (K+ and Na+) and flanking nucleotides on their geometrical characteristics, relative stability and dynamic properties. Our results show that the G-quadruplex structure is the most stable among the constructed hairpins. We confirm its topological stability through molecular dynamics simulations. Furthermore, we observe that the nucleotide loop consisting of seven nucleotides is the most flexible part of the RNA fragment. Additionally, we find that RNA networks of intermolecular hydrogen bonds are highly sensitive to the surrounding environment. Our findings reveal the loss of 79 old hydrogen bonds and the formation of 91 new ones in the case when the G-quadruplex containing flanking nucleotides is additionally stabilized by Na+ counterions.

Theoretical study of ionization and one-electron oxidation potentials of N-heterocyclic compounds.

A number of density functionals was utilized to predict gas-phase adiabatic ionization potentials (IPs) for nitrogen-rich heterocyclic compounds. Various solvation models were applied to the calculation of difference in free energies of solvation of oxidized and reduced forms of heterocyclic compounds in acetonitrile (AN) for correct reproduction of their standard oxidation potentials. We developed generally applicable protocols that could successfully predict the gas-phase adiabatic ionization potentials of nitrogen-rich heterocyclic compounds and their standard oxidation potentials in AN. This approach is supported by a MPW1K/6-31+G(d) level of theory which uses SMD(UA0) approximation for estimation of solvation energy of neutral molecules and PCM(UA0) model for ionized ones. The mean absolute derivation (MAD) and root mean square error (RMSE) of the current theoretical models for IP are equal to 0.22 V and 0.26, respectively, and for oxidation potentials MAD = 0.13 V and RMSE = 0.17.

B-DNA characteristics are preserved in double stranded d(A)3·d(T)3 and d(G)3·d(C)3 mini-helixes: conclusions from DFT/M06-2X study.

We report the results of the first comprehensive DFT study on the d(A)3·d(T)3 and d(G)3·d(C)3 nucleic acid duplexes. The ability of mini-helixes to preserve the conformation of B-DNA in the gas phase and under the influence of such factors as: solvent, uncompensated charge, and counter-ions was evaluated using M06-2X functional with 6-31G(d,p) basis set. The accuracy of the models was ascertained based on their ability to reproduce key structural features of natural B-DNA. Analysis of the helicity suggests that the helical conformations adopt geometrical parameters which are close to those of the B-DNA form. The torsion angles fall somewhere between the values observed for BI/BII conformational classes. The comparative analysis of parameters of isolated Watson-Crick base pairs versus B-DNA-like conformations indicates the same tendency of base-pair polarization and hydration. Specifically, effects of polarization of nucleobases in continuum type dielectric medium mimicking water are stronger than those caused by the presence of backbone. Polar environment as well as the presence of counterions stabilizes duplexes, facilitating helix formation. Substantial conformational changes of nucleotides upon duplex formation decrease the binding energy. In spite of structural and energetic changes, the placement of a mini-helix into the gas phase does not lead to significant disruption of the structure. On the contrary, the duplex preserves its helicity and the strands remain bound.

Manifestations of intramolecular H-bonds of CH O and OH C type in quercetin molecule: Analysis of IR spectra by mean of density functional theory.

The IR spectra of 48 conformers of quercetin which represent full conformation space of its tautomers have been modeled at B3LYP/6-311++G(d,p) level of the density functional theory. The presence of intramolecular H-bonds C2'H/C6'H…O3 and O3H…C2'/C6' was characterized by their spectral manifestations. The C2'H/C6'H…O3 contacts were found to have a spectral blue-shift. The O3H…C2'/C6' contacts were mostly red-shifted. The stretching vibrations of H-bonds C2'H/C6'H…O3 demonstrate an increase in the intensity of the modes of stretching vibrations ν(C2'H)/ν(C6'H) and an increase in the frequency of their out-of-plane vibrations γ(C2'H)/γ(C6'H). Most of the spectral parameters correlate a little with the energy of the H-bonds.

The structure of DNA fragments: Quantum-chemical modelling.

In this review, we analyze and systematize our computational studies of the nucleic acid duplex formations and thermodynamic stability under the different factors of investigation. The proposed structural models of mini-helix contains N nucleobase pairs (N = 3-5); QM structural data suggest that the helical conformations of mini-helix adopt geometrical parameters comparable to those of natural A- and B-DNA forms under specific conditions as micro hydration and charge compensation. The gas-phase models adopt non regular conformations between the helical form and a ladder form.. The natural helical shape of DNA mini-helix is stabilized by the presence of counterions or by explicit micro-hydration of the major and minor groves. The presence of aqueous solution is shown as a minor factor for the helical shape formation. The studies are performed at the level of density functional theory.

Expanding the applicability domain of QSPRs for predicting water solubility and vapor pressure of PFAS.

This work aimed to verify whether it is possible to extend the applicability domain (AD) of existing QSPR (Quantitative Structure-Property Relationship) models by employing a strategy involving additional quantum-chemical calculations. We selected two published QSPR models: for water solubility, logSW, and vapor pressure, logVP of PFAS as case studies. We aimed to enlarge set of compounds used to build the model by applying factorial planning to plan the augmentation of the set of these compounds based on their structural features (descriptors). Next, we used the COSMO-RS model to calculate the logSW and logVP for selected chemicals. This allowed filling gaps in the experimental data for further training QSPR models. We improved the published models by significantly extending number of compounds for which theoretical predictions are reliable (i.e., extending the AD). Additionally, we performed external validation that had not been carried out in original models. To test effectiveness of the AD extension, we screened 4519 PFAS from NORMAN Database. The number of compounds outside the domain was reduced comparing the original model for both properties. Our work shows that combining physics-based methods with data-driven models can significantly improve the performance of predictions of phys-chem properties relevant for the chemical risk assessment.

In silico structure-function analysis of E. cloacae nitroreductase.

Reduction, catalyzed by the bacterial nitroreductases, is the quintessential first step in the biodegradation of a variety of nitroaromatic compounds from contaminated waters and soil. The Enterobacter cloacae nitroreductase (EcNR) enzyme is considered as a prospective biotechnological tool for bioremediation of hazardous nitroaromatic compounds. Using diverse computational methods, we obtain insights into the structural basis of activity and mechanism of its function. We have performed molecular dynamics simulation of EcNR in three different states (free EcNR in oxidized form, fully reduced EcNR with benzoate inhibitor and fully reduced EcNR with nitrobenzene) in explicit solvent and with full electrostatics. Principal Component Analysis (PCA) of the variance-covariance matrix showed that the complexed nitroreductase becomes more flexible overall upon complexation, particularly helix H6, in the vicinity of the binding site. A multiple sequence alignment was also constructed in order to examine positional constraints on substitution in EcNR. Five regions which are highly conserved within the flavin mononucleotide (FMN) binding site were identified. Obtained results and their implications for EcNR functioning are discussed, and new plausible mechanism has been proposed.