Exploring the effectiveness of flavone derivatives for treating liver diseases: Utilizing DFT, molecular docking, and molecular dynamics techniques.

In exploring nature's potential in addressing liver-related conditions, this study investigates the therapeutic capabilities of flavonoids. Utilizing in silico methodologies, we focus on flavone and its analogs (1-14) to assess their therapeutic potential in treating liver diseases. Molecular change calculations using density functional theory (DFT) were conducted on these compounds, accompanied by an evaluation of each analog's physiochemical and biochemical properties. The study further assesses these flavonoids' binding effectiveness and locations through molecular docking studies against six target proteins associated with human cancer. Tropoflavin and taxifolin served as reference drugs. The structurally modified flavone analogs (1-14) displayed a broad range of binding affinities, ranging from -7.0 to -9.4 kcal mol⁻¹, surpassing the reference drugs. Notably, flavonoid (7) exhibited significantly higher binding affinities with proteins Nrf2 (PDB:1 × 2 J) and DCK (PDB:1 × 2 J) (-9.4 and -8.1 kcal mol⁻¹) compared to tropoflavin (-9.3 and -8.0 kcal mol⁻¹) and taxifolin (-9.4 and -7.1 kcal mol⁻¹), respectively. Molecular dynamics (MD) simulations revealed that the docked complexes had a root mean square deviation (RMSD) value ranging from 0.05 to 0.2 nm and a root mean square fluctuation (RMSF) value between 0.35 and 1.3 nm during perturbation. The study concludes that 5,7-dihydroxyflavone (7) shows substantial promise as a potential therapeutic agent for liver-related conditions. However, further validation through in vitro and in vivo studies is necessary. Key insights from this study include:•Screening of flavanols and their derivatives to determine pharmacological and bioactive properties using ADMET, molinspiration, and pass prediction analysis.•Docking of shortlisted flavone derivatives with proteins having essential functions.•Analysis of the best protein-flavonoid docked complexes using molecular dynamics simulation to determine the flavonoid's efficiency and stability within a system.

Synthesis, Characterization, and Environmental Applications of Novel Per-Fluorinated Organic Polymers with Azo- and Azomethine-Based Linkers via Nucleophilic Aromatic Substitution.

This study reports on the synthesis and characterization of novel perfluorinated organic polymers with azo- and azomethine-based linkers using nucleophilic aromatic substitution. The polymers were synthesized via the incorporation of decafluorobiphenyl and hexafluorobenzene linkers with diphenols in the basic medium. The variation in the linkers allowed the synthesis of polymers with different fluorine and nitrogen contents. The rich fluorine polymers were slightly soluble in THF and have shown molecular weights ranging from 4886 to 11,948 g/mol. All polymers exhibit thermal stability in the range of 350-500 °C, which can be attributed to their structural geometry, elemental contents, branching, and cross-linking. For instance, the cross-linked polymers with high nitrogen content, DAB-Z-1h and DAB-Z-1O, are more stable than azomethine-based polymers. The cross-linking was characterized by porosity measurements. The azo-based polymer exhibited the highest surface area of 770 m2/g with a pore volume of 0.35 cm3/g, while the open-chain azomethine-based polymer revealed the lowest surface area of 285 m2/g with a pore volume of 0.0872 cm3/g. Porous structures with varied hydrophobicities were investigated as adsorbents for separating water-benzene and water-phenol mixtures and selectively binding methane/carbon dioxide gases from the air. The most hydrophobic polymers containing the decafluorbiphenyl linker were suitable for benzene separation, while the best methane uptake values were 6.14 and 3.46 mg/g for DAB-Z-1O and DAB-A-1O, respectively. On the other hand, DAB-Z-1h, with the highest surface area and being rich in nitrogen sites, has recorded the highest CO2 uptake at 298 K (17.25 mg/g).

Synthesis, Characterization, and DFT Calculations of a New Sulfamethoxazole Schiff Base and Its Metal Complexes.

A new Schiff base, 4-((1E,2E)-3-(furan-2-yl)allylidene)amino)-N-(5-methylisoxazol-3-yl) benzene-sulfonamide (L), was synthesized by thermal condensation of 3-(2-furyl)acrolein and sulfamethoxazole (SMX), and the furan Schiff base (L) was converted to a phenol Schiff base (L') according to the Diels-Alder [4 + 2] cycloaddition reaction and studied experimentally. The structural and spectroscopic properties of the Schiff base were also corroborated by utilizing density functional theory (DFT) calculations. Furthermore, a series of lanthanide and transition metal complexes of the Schiff base were synthesized from the nitrate salts of Gd, Sm, Nd, and Zn (L1, L2, L3, and L4), respectively. Various spectroscopic studies confirmed the chemical structures of the Schiff-base ligand and its complexes. Based on the spectral studies, a nine-coordinated geometry was assigned to the lanthanide complexes and a six-coordinated geometry to the zinc complex. The elemental analysis data confirmed the suggested structure of the metal complexes, and the TGA studies confirmed the presence of one coordinated water molecule in the lanthanide complexes and one crystalline water molecule in the zinc complex; in addition, the conductivity showed the neutral nature of the complexes. Therefore, it is suggested that the ligand acts as a bidentate through coordinates to each metal atom by the isoxazole nitrogen and oxygen atoms of the sulfur dioxide moiety of the SMX based on FTIR studies. The ligand and its complexes were tested for their anti-inflammatory, anti-hemolytic, and antioxidant activities by various colorimetric methods. These complexes were found to exhibit potential effects of the selected biological activities.

Thermal decomposition of perfluorinated carboxylic acids: Kinetic model and theoretical requirements for PFAS incineration.

Thermal decomposition of high-fluorine content PFAS streams for the disposal of old generations of concentrates of firefighting foams, exhausted ion-exchanged resins and granular activated carbon, constitutes the preferred method for destruction of these materials. This contribution studies the thermal transformation of perfluoropentanoic acid (C4F9C(O)OH, PFPA), as a model PFAS species, in gas-phase reactions over broad ranges of temperature and residence time, which characterise incinerators and cement kilns. Our focus is only on gas-phase reactions, to formulate a gas-phase submodel that, in future, could be used in comprehensive simulation of thermal destruction of PFAS; such comprehensive models will need to comprise fluorine mineralisation on flyash and in clinker material. Our submodel consists of 56 reactions and 45 species, and includes new pathways that cover the initial decomposition channels of PFPA, including those that lead to the formation of the n-C4F9 radical, the abstraction of hydroxyl H by O/H radicals, the fragmentation of the n-C4F9 radical, reactions between HF and perfluoropentanoic acid, as well as between HF and heptafluorobutanoyl fluoride (C3F7COF), and the cyclisation reactions. The model illustrates the formation of a wide spectrum of small CnFm and CnHFm compounds in the temperature window of 800-1500 K, 2 and 25 s residence time in a plug flow reactor, providing theoretical estimates for the operating conditions of PFAS thermal destruction systems. The initiation reactions involve the loss of HF and formation of the transition α-lactone species that converts to C3F7COF, with C4F9C(O)OH completely decomposed at 1020 K for 2 s residence time. At 1500 K, we predict the emission of ꞉CF2 (biradical difluorocarbene), HF, CO2, CO, CF4, C2F6, and C2F4, but at < 1400 K, we note the formation of 1H-nonafluorobutane (C4HF9), phosgene (COF2), and heptafluorobutanoyl fluoride (C3F7COF), with 1-C4F8, 2-C4F8 and C3HF7 persisting to 1500 K. We demonstrate that, the gas-phase pyrolysis processes by themselves convert PFAS to HF and short-chain fluorocarbons, with similar product distribution for short (2 s) and long (25 s) residence times, as long as the treatment temperature exceeds 1500 K. These residence times reflect those encountered in incinerators and cement kilns, respectively. Thermokinetic and mechanistic insights revealed herein shall assist to innovate PFAS thermal disposal technologies, and, from a fundamental perspective, to accelerate research progress in modelling of gas/solid reactions that mineralise PFAS-derived fluorine.

Thermal Degradation and Bimolecular Decomposition of 2-Ethoxyethanol in Binary Ethanol and Isobutanol Solvent Mixtures: A Computational Mechanistic Study.

A thorough computational study of a thermal degradation mechanism of 2-ethoxyethanol (2-EE) in the gas phase has been implemented using G3MP2 and G3B3 methods. The stationary point geometries were optimized at the B3LYP functional utilizing the 6-31G(d) basis set. Intrinsic reaction coordinate analysis was performed to determine the transition states on the potential energy surfaces. Nineteen primary different reaction mechanisms, along with the kinetic and thermodynamic parameters, are demonstrated. Most of the thermal degradation mechanisms result in a concerted transition state step as an endothermic process. Among 11 degradation pathways of 2-ethoxyethanol, the formation of ethylene glycol and ethylene is kinetically significant with an activation energy of 269 kJ mol-1 at the G3B3 method. However, the kinetic and thermodynamic calculations indicate that ethanol and ethanal's formation is the most plausible reaction with an activation barrier of 287 kJ mol-1 at the G3B3 method. For the bimolecular dissociation reaction of 2-ethoxyethanol with ethanol, the pathway that produces ether, H2, and ethanol is more likely to occur with a lower activation energy of 221 kJ mol-1 at the G3B3 method. Thus, 2-EE has experienced a set of complex unimolecular and bimolecular reactions.

Thiacrown Ethers Engaged C60 through Charge Transfer: Experimental and Theoretical Study.

UV-Vis spectroscopy is used to study the charge transfer complexes of thiacrown ethers 1-6 with fullerene. The size of TCE1-6 and the nature of the heteroatoms (N, O and S) have been systematically changed to examine the effect of these factors on the HOMO/LUMO energy levels, the optical energy gap and the interactions between TCE's and C60. The negative and positive values of ΔS designate the structural forming method and the randomness of the free solvent molecules, respectively. Thermodynamics and stability data show that the complexes have a 1:1 ratio that has been emphasized by density functional theory calculations. Additionally, they show a synergetic interplay of donor-acceptor, π-π, and n-π interactions, which are the basis for the affinity of our novel receptors toward C60. The proposed system of enzyme model suggests a development concept in the future design of enzyme model organic photovoltaic systems.

Computational mechanistic study of the unimolecular dissociation of ethyl hydroperoxide and its bimolecular reactions with atmospheric species.

A detailed computational study of the atmospheric reaction of the simplest Criegee intermediate CH2OO with methane has been performed using the density functional theory (DFT) method and high-level calculations. Solvation models were utilized to address the effect of water molecules on prominent reaction steps and their associated energies. The structures of all proposed mechanisms were optimized using B3LYP functional with several basis sets: 6-31G(d), 6-31G (2df,p), 6-311++G(3df,3pd) and at M06-2X/6-31G(d) and APFD/6-31G(d) levels of theory. Furthermore, all structures were optimized at the B3LYP/6-311++G(3df,3pd) level of theory. The intrinsic reaction coordinate (IRC) analysis was performed for characterizing the transition states on the potential energy surfaces. Fifteen different mechanistic pathways were studied for the reaction of Criegee intermediate with methane. Both thermodynamic functions (ΔH and ΔG), and activation parameters (activation energies Ea, enthalpies of activation ΔHǂ, and Gibbs energies of activation ΔGǂ) were calculated for all pathways investigated. The individual mechanisms for pathways A1, A2, B1, and B2, comprise two key steps: (i) the formation of ethyl hydroperoxide (EHP) accompanying with the hydrogen transfer from the alkanes to the terminal oxygen atom of CIs, and (ii) a following unimolecular dissociation of EHP. Pathways from C1 → H1 involve the bimolecular reaction of EHP with different atmospheric species. The photochemical reaction of methane with EHP (pathway E1) was found to be the most plausible reaction mechanism, exhibiting an overall activation energy of 7 kJ mol-1, which was estimated in vacuum at the B3LYP/6-311++G(3df,3pd) level of theory. All of the reactions were found to be strongly exothermic, expect the case of the sulfur dioxide-involved pathway that is predicted to be endothermic. The solvent effect plays an important role in the reaction of EHP with ammonia (pathway F1). Compared with the gas phase reaction, the overall activation energy for the solution phase reaction is decreased by 162 and 140 kJ mol-1 according to calculations done with the SMD and PCM solvation models, respectively.

Computational study of the unimolecular and bimolecular decomposition mechanisms of propylamine.

A detailed computational study of the dehydrogenation reaction of trans-propylamine (trans-PA) in the gas phase has been performed using density functional method (DFT) and CBS-QB3 calculations. Different mechanistic pathways were studied for the reaction of n-propylamine. Both thermodynamic functions and activation parameters were calculated for all investigated pathways. Most of the dehydrogenation reaction mechanisms occur in a concerted step transition state as an exothermic process. The mechanisms for pathways A and B comprise two key-steps: H2 eliminated from PA leading to the formation of allylamine that undergoes an unimolecular dissociation in the second step of the mechanism. Among these pathways, the formation of ethyl cyanide and H2 is the most significant one (pathway B), both kinetically and thermodynamically, with an energy barrier of 416 kJ mol-1. The individual mechanisms for the pathways from C to N involve the dehydrogenation reaction of PA via hydrogen ion, ammonia ion and methyl cation. The formation of α-propylamine cation and NH3 (pathway E) is the most favorable reaction with an activation barrier of 1 kJ mol-1. This pathway has the lowest activation energy calculated of all proposed pathways.

Probing the Reactivity of Singlet Oxygen with Cyclic Monoterpenes.

Monoterpenes represent a class of hydrocarbons consisting of two isoprene units. Like many other terpenes, monoterpenes emerge mainly from vegetation, indicating their significance in both atmospheric chemistry and pharmaceutical and food industries. The atmospheric recycling of monoterpenes constitutes a major source of secondary organic aerosols. Therefore, this contribution focuses on the mechanism and kinetics of atmospheric oxidation of five dominant monoterpenes (i.e., limonene, α-pinene, ß-pinene, sabinene, and camphene) by singlet oxygen. The reactions are initiated via the ene-type addition of singlet oxygen (O2 1Δg) to the electron-rich double bond, progressing favorably through the concerted reaction mechanisms. The physical analyses of the frontier molecular orbitals agree well with the thermodynamic properties of the selected reagents, and the computed reaction rate parameters. The reactivity of monoterpenes with O2 1Δg follows the order of α-pinene > sabinene > limonene > ß-pinene > camphene, i.e., α-pinene and camphene retain the highest and lowest reactivity toward singlet oxygen, with rate expressions of k(T) (M-1 s-1) = 1.13 × 108 exp(-48(kJ)/RT(K)) and 6.93 × 108 exp(-139(kJ)/RT(K)), respectively. The effect of solvent on the primary reaction pathways triggers a slight reduction in energy, ranging between 12 and 34 kJ/mol.

Unimolecular Decomposition Reactions of Propylamine and Protonated Propylamine.

A detailed computational study of the decomposition reaction mechanisms of cis-propylamine (cis-PA), trans-propylamine (trans-PA), and the cis-isomer of its protonated form (cis-HPA) has been carried out. Fourteen major pathways with their kinetic and thermodynamic parameters are reported. All reported reactions have been located with a concerted transition state, leading to significant products that agree with previous theoretical and experimental studies. Among six decomposition pathways of trans-PA, the formation of propene and NH3 is the significant one, kinetically and thermodynamically, with an activation energy barrier of 281 kJ mol-1. The production of two carbenes is found via two different transition states, where the reactions are thermodynamically controlled and reversible. Furthermore, five decomposition pathways of cis-PA have been considered where the formation of ethene, methylimine, and H2 is the most plausible one with an activation energy barrier of 334 kJ mol-1. The results show that the formation of propene and NH4 + from the decomposition of cis-HPA is the most favorable reaction with an activation barrier of 184 kJ mol-1, that is, the lowest activation energy calculated for all decomposition pathways.

Catalytic Hydrogenation of p-Chloronitrobenzene to p-Chloroaniline Mediated by γ-Mo2N.

Promoting the production of industrially important aromatic chloroamines over transition-metal nitrides catalysts has emerged as a prominent theme in catalysis. This contribution provides an insight into the reduction mechanism of p-chloronitrobenzene (p-CNB) to p-chloroaniline (p-CAN) over the γ-Mo2N(111) surface by means of density functional theory calculations. The adsorption energies of various molecularly adsorbed modes of p-CNB were computed. Our findings display that, p-CNB prefers to be adsorbed over two distinct adsorption sites, namely, Mo-hollow face-centered cubic (fcc) and N-hollow hexagonal close-packed (hcp) sites with adsorption energies of -32.1 and -38.5 kcal/mol, respectively. We establish that the activation of nitro group proceeds through direct pathway along with formation of several reaction intermediates. Most of these intermediaries reside in a significant well-depth in reference to the entrance channel. Central to the constructed mechanism is H-transfer steps from fcc and hcp hollow sites to the NO/-NH groups through modest reaction barriers. Our computed rate constant for the conversion of p-CNB correlates very well with the experimental finding (0.018 versus 0.033 s-1 at ∼500 K). Plotted species profiles via a simplified kinetics model confirms the experimentally reported high selectivity toward the formation of p-CAN at relatively low temperatures. It is hoped that thermokinetics parameters and mechanistic pathways provided herein will afford a molecular level understanding for γ-Mo2N-mediated conversion of halogenated nitrobenzenes into their corresponding nitroanilines; a process that entails significant industrial applications.

Hydration and Secondary Ozonide of the Criegee Intermediate of Sabinene.

A computational study of the formation of secondary ozonide (SOZ) from the Criegee intermediates (CIs) of sabinene, including hydration reactions with H2O and 2H2O, was performed. All of the geometries were optimized at the B3LYP and M06-2X with several basis sets. Further single-point energy calculation at the CCSD(T) was performed. Two major pathways of SOZ formation suggest that it is mainly formed from the sabinene CI and formaldehyde rather than sabina ketone and formaldehyde-oxide. However, in both pathways, the activation energies are within a range of ±5 kJ mol-1. Furthermore, the hydration reactions of the anti-CI with H2O and 2H2O showed that the role of the second water molecule is a mediator (catalyst) in this reaction. The dimer hydration reaction has lower activation energies than the monomer by 60 and 69 kJ mol-1, at the M06-2X/6-31G(d) and CCSD(T)+CF levels of the theory, respectively. A novel water-mediated vinyl hydroperoxide (VHP) channel from both the monomer and dimer has been investigated. The results indicate that the direct nonmediated VHP formation and dissociation is interestingly more possible than the water-mediated VHP. The density functional theory calculations show that the monomer is faster than the dimer by roughly 22 kJ mol-1. Further, the infrared spectrum of sabina ketone was calculated at B3LYP/6-311+G(2d,p); the calculated carbonyl stretching of 1727 cm-1 is in agreement with the experimental range of 1700-1800 cm-1.

Mechanistic study of the deamidation reaction of glutamine: a computational approach.

Glutamine--a popular nutritional supplement, non-toxic amino acid, and an essential interorgan and intercellular ammonia transporter--can destroy the neurons' mitochondria. When glutamine enters (like a Trojan horse) into the mitochondria, in the presence of glutaminase, it reacts with water and yields glutamate and excess ammonia which opens gates in the membrane of the mitochondria and thereby destroys it. The mechanistic details underlying the molecular basis of the catabolic production of excess ammonia remain unclear. In the present paper, both 5-oxoproline-mediated and direct pathways for glutamine deamidation are studied using wave function and density functional theories. The mechanisms are studied both in the gas phase and in aqueous solution using the polarizable continuum model (PCM) and solvent model on density (SMD) solvation models. Among three glutamine deamidation pathways, a two-step pathway, GDB, shows the lowest gas phase barrier height of 189 kJ/mol with the G3MP2B3 level of theory. Incorporation of solvent through PCM and SMD models reduces the barrier height to 183 and 174 kJ/mol, respectively. For the hydrolysis of 5-oxoproline, a two-step mechanism, pathway PH-B, provides a lower gas phase energy barrier (187 kJ/mol) compared to one-step (201 kJ/mol) and three-step (227 kJ/mol) pathways at G3MP2B3. Although direct hydrolysis with OH(-), pathway DHE, has the lowest gas phase barrier of 135 kJ/mol, the solvent has little effect on the barrier. For the direct hydrolysis with OH(-)/H2O, pathway DHF, the overall barrier is 143 kJ/mol, in the gas phase at G3MP2B3. In aqueous solution, the overall barrier decreases to 76 and 75 kJ/mol with PCM and SMD, respectively, at B3LYP/6-31+G(d,p), making this the most plausible mechanism. Compared to PCM, SMD predicts lower barriers for nearly all pathways investigated.

Theoretical investigation into competing unimolecular reactions encountered in the pyrolysis of acetamide.

Motivated by the necessity to understand the pyrolysis of alkylated amines, unimolecular decomposition of acetamide is investigated herein as a model compound. Standard heats of formation, entropies, and heat capacities, are calculated for all products and transition structures using several accurate theoretical levels. The potential energy surface is mapped out for all possible channels encountered in the pyrolysis of acetamide. The formation of acetamedic acid and 1-aminoethenol and their subsequent decomposition pathways are found to afford the two most energetically favored pathways. However, RRKM analysis shows that the fate of acetamedic acid and 1-aminoethenol at all temperatures and pressures is to reisomerize to the parent acetamide. 1-Aminoethenol, in particular, is predicted to be a long-lived species enabling its participation in bimolecular reactions that lead to the formation of the major experimental products. Results presented herein reflect the importance of bimolecular reactions involving acetamide and 1-aminoethenol in building a robust model for the pyrolysis of N-alkylated amides.

Theoretical study on the unimolecular decomposition of thiophenol.

The potential energy surface for the unimolecular decomposition of thiophenol (C(6)H(5)SH) is mapped out at two theoretical levels; BB1K/GTlarge and QCISD(T)/6-311+G(2d,p)//MP2/6-31G(d,p). Calculated reaction rate constants at the high pressure limit indicate that the major initial channel is the formation of C(6)H(6)S at all temperatures. Above 1000 K, the contribution from direct fission of the S-H bond becomes important. Other decomposition channels, including expulsion of H(2) and H(2)S are of negligible importance. The formation of C(6)H(6)S is predicted to be strong-pressure dependent above 900 K. Further decomposition of C(6)H(6)S produces CS and C(5)H(6). Overall, despite the significant difference in bond dissociation, i.e., 8-9 kcal/mol between the S-H bond in thiophenol and the O-H bond in phenol, H migration at the ortho position in the two molecules represents the most accessible initial channel.

Mechanistic study of the deamination reaction of guanine: a computational study.

The mechanism for the deamination of guanine with H(2)O, OH(-), H(2)O/OH(-) and for GuaH(+) with H(2)O has been investigated using ab initio calculations. Optimized geometries of the reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), B3LYP/6-31G(d), and B3LYP/6-31+G(d) levels of theory. Energies were also determined at G3MP2, G3MP2B3, G4MP2, and CBS-QB3 levels of theory. Intrinsic reaction coordinate (IRC) calculations were performed to characterize the transition states on the potential energy surface. Thermodynamic properties (ΔE, ΔH, and ΔG), activation energies, enthalpies, and Gibbs free energies of activation were also calculated for each reaction investigated. All pathways yield an initial tetrahedral intermediate and an intermediate in the last step that dissociates to products via a 1,3-proton shift. At the G3MP2 level of theory, deamination with OH(-) was found to have an activation energy barrier of 155 kJ mol(-1) compared to 187 kJ mol(-1) for the reaction with H(2)O and 243 kJ mol(-1) for GuaH(+) with H(2)O. The lowest overall activation energy, 144 kJ mol(-1) at the G3MP2 level, was obtained for the deamination of guanine with H(2)O/OH(-). Due to a lack of experimental results for guanine deamination, a comparison is made with those of cytosine, whose deamination reaction parallels that of guanine.

Mechanisms for the deamination reaction of cytosine with H2O/OH(-) and 2H2O/OH(-): a computational study.

Mechanisms for the deamination reaction of cytosine with H 2O/OH (-) and 2H 2O/OH (-) to produce uracil were investigated using ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and products were determined at MP2 and B3LYP using the 6-31G(d) basis set and at B3LYP/6-31+G(d) levels of theory. Single point energies were also determined at MP2/G3MP2Large and G3MP2 levels of theory. Thermodynamic properties (Delta E, Delta H, and Delta G), activation energies, enthalpies, and free energies of activation were calculated for each reaction pathway investigated. Intrinsic reaction coordinate (IRC) analysis was performed to characterize the transition states on the potential energy surface. Seven pathways for the deamination reaction were found. All pathways produce an initial tetrahedral intermediate followed by several conformational changes. The final intermediate for all pathways dissociates to product via a 1-3 proton shift. The activation energy for the rate-determining step, the formation of the tetrahedral intermediate for pathway D, the only pathway that can lead to uracil, is 115.3 kJ mol (-1) at the G3MP2 level of theory, in excellent agreement with the experimental value (117 +/- 4 kJ mol (-1)).

Computational study of the deamination reaction of cytosine with H2O and OH-.

The mechanism for the deamination reaction of cytosine with H(2)O and OH(-) to produce uracil was investigated using ab initio calculations. Optimized geometries of reactants, transition states, intermediates, and products were determined at RHF/6-31G(d), MP2/6-31G(d), and B3LYP/6-31G(d) levels and for anions at the B3LYP/6-31+G(d) level. Single-point energies were also determined at B3LYP/6-31+G(d), MP2/GTMP2Large, and G3MP2 levels of theory. Thermodynamic properties (DeltaE, DeltaH, and DeltaG), activation energies, enthalpies, and free energies of activation were calculated for each reaction pathway that was investigated. Intrinsic reaction coordinate analysis was performed to characterize the transition states on the potential energy surface. Two pathways for deamination with H(2)O were found, a five-step mechanism (pathway A) and a two-step mechanism (pathway B). The activation energy for the rate-determining steps, the formation of the tetrahedral intermediate for pathway A and the formation of the uracil tautomer for pathway B, are 221.3 and 260.3 kJ/mol, respectively, at the G3MP2 level of theory. The deamination reaction by either pathway is therefore unlikely because of the high barriers that are involved. Two pathways for deamination with OH(-) were also found, and both of them are five-step mechanisms. Pathways C and D produce an initial tetrahedral intermediate by adding H(2)O to deprotonated cytosine which then undergoes three conformational changes. The final intermediate dissociates to product via a 1-3 proton shift. Deamination with OH(-), through pathway C, resulted in the lowest activation energy, 148.0 kJ/mol, at the G3MP2 level of theory.