Tautomeric Transformations Research Articles

Synthesis and DFT-optimized structures of hydrazonal-based compound: Biological activity and molecular docking

Distinctive quinolinyl hydrazonal-based compound was synthesized by an azo-coupling reaction of an enaminonitrile (piperidinylacrylonitrile) with the diazonium salt of 8-aminoquinoline. The synthesized compound was characterized by different spectroscopic methods and displayed distinctive solvatochromism. The possible tautomeric transformation of the arylhydrazonal was studied using DFT quantum chemical calculations revealing that the E→Z tautomerization was a spontaneous exothermic process and its equilibrium constant (Keq) was high with positive power. Thus, the Z-tautomer is more favorable than E-tautomer. This study looks at arylhydrazonal's multiple biological actions, showing its substantial promise in antibacterial, antifungal, anticancer, and enzyme inhibition applications. The arylhydrazonal exhibited concentration-dependent strong antibacterial action against Gram-positive and negative bacteria. Moreover, it showed a comparable concentration-dependent antifungal efficiency against C. albicans and A. fumigatus, and close to fluconazole's potency against A. fumigatus. The arylhydrazonal exhibits significant anticancer action, targeting skin and breast cancer cells, suggesting lesser harm to normal cells. In comparison with acetazolamide (AZA), It inhibited carbonic anhydrase isozymes IX and XII with substantial potency against CA-XII. Molecular docking investigations demonstrated the compound's interactions with proteins such 1D2S, 1AS0, 4WW8, and 5Fl4, revealing different binding energies, RMSD values, and stable configurations via hydrogen bonding and π-H stacking interactions. These results highlight the compound's potential as a therapeutic agent in a variety of clinical applications, calling for more study into its development and clinical usage.

Effect of cationic Gemini surfactants ethonium and decamethoxin on the spectral properties, solubility and tautomerism of the curcumin

AbstractThe properties of natural polyphenol curcumin in water solutions of cationic Gemini surfactants decamethoxin and ethonium, which have similar positively charged nitrogen hydrophilic head groups but different spacer sizes and lengths of hydrophobic tails have been investigated in a wide range of concentrations by using UV–Vis spectroscopy and quantum‐chemical calculations. It was found that curcumin dissolves in the organized micellar media of these surfactants in the enol tautomeric form and its solubility increases 400 times compared to water. The binding constants of curcumin with decamethoxin and ethonium were determined by the solubility method. Significant differences in the influence of premicellar concentrations of cationic Gemini surfactants on the solubility and tautomeric transformations of curcumin were revealed. In contrast to decamethoxin, ethonium at a concentration below the CMC promotes a significant increase in the solubility of curcumin and a shift in the tautomeric equilibrium towards the formation of its keto form.

Hydrogen-atom tunneling in small thioamides: N-methylthiourea, thiobenzamide and 2-cyanothioacetamide

The most stable thione tautomeric forms of N-methylthiourea, thiobenzamide and 2-cyanothioacetamide were isolated in low-temperature argon matrices. The higher-energy thiol tautomers of these compounds were generated upon irradiation of matrix-isolated monomers with UV (λ > 270 nm) light. For N-methylthiourea and thiobenzamide, kept in the dark at 3.5 K for a long period of time, a spontaneous thiol → thione hydrogen atom tunneling transformation occurred. Only the thiol isomers with the favorably oriented hydrogen atom of the imino group underwent these hydrogen-atom tunneling processes. The other thiol isomers, with the hydrogen atom of the imino group oriented towards the sulfur atom, did not undergo the thiol → thione conversion. For the photogenerated thiol forms of 2-cyanothioacetamide, no spontaneous thiol → thione tautomeric transformation was detected. Instead, only the spontaneous conformational change of one S-H rotamer of the thiol 2-cyanothioacetamide tautomer into the other S-H rotamer was observed.

Effect of Tautomerization on Water Desalination by Covalent Organic Frameworks

Covalent organic frameworks (COFs) have gained increasing interest as promising building blocks for desalination membranes due to their inherent porosity. Efforts have been made to prepare COF membranes and explore their transport mechanisms, however the effect of tautomerization has not been reported. Using non-equilibrium molecular dynamics, we discover here that a mere 0.5-Å atomic displacement between two tautomers of an imine-based COF (TpHZ) can surprisingly lead to dramatic changes in the desalination behavior of their multilayers. The tautomeric transformation (from TpHZ-NH to TpHZ-OH) improves the water permeability by about 1.6–3 times. The interior resistance rather than the entrance resistance is found to dominate the water transport. The weaker adhesion and the smoother channel path of TpHZ-OH result in a much lower interior resistance. Furthermore, NaCl rejection increases from ∼ 89 % to 100 % due to the stronger sieving effect resulting from the reduced compensatory effect of TpHZ-OH for ion hydrations.

Valence tautomeric interconversion of bis-dioxolene cobalt complex with imino-pyridine functionalized by TEMPO moiety in solid solutions with isostructural nickel analogue: phase transitions and monocrystal destruction.

Valence tautomeric complexes (VT) are promising systems for creating molecular devices. From this viewpoint, valence tautomeric complexes with a hysteresis loop on the magnetic curve are of special interest as potential memory elements. The hysteresis loop is a consequence of retarded structural rearrangements which investigation is an actual problem. Recently, we have described a new VT transition taking place in a bis-dioxolene cobalt complex with imino-pyridine having a TEMPO substituent (A. A. Zolotukhin, et al., Inorg. Chem., 2017, 56, 14751-14754). Valence tautomeric transformation occurs with a hysteresis loop and is accompanied by a phase transition. The phase transition taking place during cooling is accompanied by crystal destruction. This fact makes it impossible to monitor the structural changes responsible for the hysteresis loop. The current research attempts to resolve this problem. A nickel compound of the same composition (TEMPO-imino-pyridine)Ni(3,6-DBSQ)2 was synthesized and characterized. It was established to be isostructural with the cobalt complex. It was used as an inert matrix for the dilution of the VT cobalt complex. The number of solid solutions with Co/Ni ratios of 1 : 1, 1 : 2, 1 : 4, and 1 : 8 was obtained. Variable temperature magnetic susceptibility measurements show that VT transformation with a hysteresis loop takes place in all solid solutions. The hysteresis loop is shifted to low temperatures primarily due to the shifting of its low-temperature boundary with dilution. The hysteresis width does not change significantly with dilution. DSC detected that transformations are accompanied by phase transitions at different temperatures at cooling and heating. The phase transition at the first cooling occurs at slightly lower temperatures compared with subsequent cycles. These temperatures correspond to the transition temperatures detected from the magnetic curves. The phase transition during the first cooling is accompanied by crystal destruction. Physical destruction takes place in the crystals of all solid solutions. X-ray diffraction powder patterns confirm that phase transition is accompanied by considerable reorganization of the crystal structure typical for the first order transitions. The unit cell volume of solid solutions is larger than that of pure complexes. Especially calculated crystal invariom indicated that the "lattice energy" in a solid solution is the lowest compared with that in "pure" nickel and cobalt complexes.

Acyl derivatives of 2,3,6,7-tetrahydro-1,4-diazepines: synthesis, structure, and tautomeric transformations

The reaction of 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene with carboxylic acid chlorides afforded a series of N -and C -acylsubstituted 2,3,6,7-tetrahydro-1,4-diazepines, which in solutions of deuterated solvents (CD3OD, DMCO) undergo keto-enol and imino-enamine tautomerism. Structure of the obtained N - and C -acyldiazepines and their tautomeric transformations were characterized by 1Н and 13С NMR spectroscopy using two-dimensional experiments 1Н-13С HMQC, HMBC, 1Н-1Н COSY.

Acyl Derivatives of 2,3,6,7-Tetrahydro-1,4-diazepines: Synthesis, Structure, and Tautomeric Transformations

Acyl Derivatives of 2,3,6,7-Tetrahydro-1,4-diazepines: Synthesis, Structure, and Tautomeric Transformations

MolTaut: A Tool for the Rapid Generation of Favorable Tautomer in Aqueous Solution.

Fast and proper treatment of the tautomeric states for drug-like molecules is critical in computer-aided drug discovery since the major tautomer of a molecule determines its pharmacophore features and physical properties. We present MolTaut, a tool for the rapid generation of favorable states of drug-like molecules in water. MolTaut works by enumerating possible tautomeric states with tautomeric transformation rules, ranking tautomers with their relative internal energies and solvation energies calculated by AI-based models, and generating preferred ionization states according to predicted microscopic pKa. Our test shows that the ranking ability of the AI-based tautomer scoring approach is comparable to the DFT method (wB97X/6-31G*//M062X/6-31G*/SMD) from which the AI models try to learn. We find that the substitution effect on tautomeric equilibrium is well predicted by MolTaut, which is helpful in computer-aided ligand design. The source code of MolTaut is freely available to researchers and can be accessed at https://github.com/xundrug/moltaut. To facilitate the usage of MolTaut by medicinal chemists, we made a free web server, which is available at http://moltaut.xundrug.cn. MolTaut is a handy tool for investigating the tautomerization issue in drug discovery.

Solubilization and Tautomeric Transformations of Natural Curcumin Dye into Aqueous Solution of Cationic Dimeric Surfactant Decamethoxine

Solubilization and Tautomeric Transformations of Natural Curcumin Dye into Aqueous Solution of Cationic Dimeric Surfactant Decamethoxine

Determination of ionization constants for sequinidazole in aqueous solutions and mixtures of water with isopropanol, acetonitrile and ethanol

Seknidazole is a drug from the 5-nitroimidazole group with a number of side-effects. This drug is virtually unexplored from the point of view of chemico-toxicological analysis (CTA). Therefore, the development of a set of methods for the detection and quantification of secnidazole in biological fluids for use in CTA is an urgent task. Aim. To study the acid-base equilibrium of secnidazole in aqueous solutions and mixtures of water with amphiphilic solvents and determine the corresponding ionization constants. Materials and methods. Spectrophotometric measurements were performed using a SPEKOL®1500 single-beam spectrophotometer. An EV-74 ionomer was used to control the pH of the solutions. Seknidazole solutions in the concentrationof 1000 μg/ml were used in the experiment. Results and discussion. Absorption spectra of secnidazole in water and mixtures of water and amphiphilic solvents in the pH range studied showed four isobestic points characterizing two protolytic equilibria (equilibrium 1 – 240 and 295 nm, equilibrium 2 – 261 and 297 nm). The position of the isobestic points of equilibrium 2 fluctuated in the range ± 3 nm; it was due to the presence of tautomeric transformations for the molecular form of secnidazole. Conclusions. The acid-base equilibria of secnidazole in aqueous solutions and mixtures of water with amphiphilic solvents have been studied. It has been shown that in a strongly alkaline medium there is an anionic form of secnidazole R–, with further decrease in the pH value the molecular form HR appears, in a strongly acidic medium the final product – a protonated form H2R+ – is formed. The ionization constant 1 has been determined for aqueous solutions of secnidazole, mixtures of water with isopropanol, acetonitrile and ethanol. It is impossible to determine the equilibrium constant 2 by the method specified.

Valence tautomerism in cobalt complexes based on isopropyl- and cyclohexyl-substituted o-quinones

A series of novel dioxolene cobalt complexes with general formula (N-N)Co(3,6-diox)2 (where N-N = 2,2′-dipyridine (bpy) and 1,10-phenanthroline (phen), diox – mono- and dianionic forms of 3,6-di-isopropyl-o-benzoquinone (3,6-iPr-Q) and 3,6-di-cyclohexyl-o-benzoquinone (3,6-cHex-Q)) has been synthesized and characterized. The molecular structures of dipyridine adducts have been established by single crystal X-Ray structural analysis. Magnetic susceptibility measurements detect solid-state valence-tautomeric transformation occurring for complexes (phen)Co(3,6-iPr-SQ)2 and (bpy)Co(3,6-cHex-SQ)2. The phase transitions that accompany valence tautomeric transformation have been investigated by differential scanning calorimetry (DSC).

Atomistic mechanisms of the tautomerization of the G·C base pairs through the proton transfer: quantum-chemical survey.

This study is devoted to the investigation of the G·C*tO2(WC)↔G*NH3·C*t(WC), G·C*O2(WC)↔G*NH3·C*(WC) and G*·C*O2(WC)↔G*NH3·C(wWC)↓ tautomerization reactions occurring through the proton transfer, obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in gas phase under normal conditions ('WC' means base pair in Watson-Crick configuration, T=298.15 K). These reactions lead to the formation of the G*NH3·C*t(WC), G*NH3·C*(WC) and G*NH3·C(wWC)↓ base pairs by the participation of the G*NH3 base with NH3 group. Gibbs free energies of activation for these reactions are 6.43, 11.00 and 1.63 kcal·mol-1, respectively. All of these tautomerization reactions are dipole active. Finally, we believe that these non-dissociative processes, which are tightly connected with the tautomeric transformations of the G·C base pairs, play an outstanding role in supporting of the spatial structure of the DNA and RNA molecules with various functional purposes.

In-depth insight into the inhibition mechanism of pyrimidine derivatives on the corrosion of carbon steel in CO2-containing environment based on experiments and theoretical calculations

In this work, with 2-mercaptopyrimidine (MP) as the precursor, a pyrimidine derivative, 2-benzylthiopyrimidine (BTP), is developed as inhibitor to inhibit the corrosion of carbon steel in CO2-containing environment. Electrochemical measurements indicate that MP and BTP present high inhibition performance, especially for BTP with an inhibition efficiency of 99.82 %. Theoretical calculations show that the protonation of MP and BTP hardly occurs. The benzyl substituent in BTP enhances its adsorption ability by preventing tautomeric transformation and forming hydrophobic structure. Both MP and BTP molecules can adsorb on Fe surface in a nearly vertical orientation through the bonding of N and S atoms.

Valence tautomeric transformation in the [CrCo] compound: exploration of cooperative interactions.

A crystal containing the heterometallic Cr-ligand-Co cluster with an unpaired electron on the ligand as a structural unit is examined. The developed model which describes the magnetic and polarizability characteristics of this crystal takes into account that the electron residing on the ligand can be transferred to the Co-ion, thus converting the diamagnetic ls-CoIII ion into the paramagnetic hs-CoII one. Since this transformation is accompanied by electron density redistribution and elongation of the Co-N bond lengths, the vibronic interaction of the Co-ion with totally symmetric displacements of the nearest surroundings and cooperative dipole-dipole and electron-deformational interactions are accounted for as well. The exchange interactions between the CrIII ion and the electron localized on the ligand as well as in the CrIII-hs-CoII pair are also included in consideration; the parameters of these interactions are estimated within the framework of the DFT method. Bistability in the magnetic and polarization characteristics is predicted for certain strengths of intra- and intercluster interactions in the crystal under study. Within the framework of the developed approach an explanation of the observed magnetic properties of the [Cr(SS-cth)(Co(RR-cth)(μ-dhbq))](PF6)2Cl crystal is given.

A Quantum-Mechanical Looking Behind the Scene of the Classic G·C Nucleobase Pairs Tautomerization.

For the first time, at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory, a comprehensive quantum-mechanical investigation of the physico-chemical mechanism of the tautomeric wobblization of the four biologically-important G·C nucleobase pairs by the participation of the monomers in rare, in particular mutagenic, tautomeric forms (marked with an asterisk) was provided. These novel tautomeric transformations (wobblization or shifting of the bases within the pair) are intrinsically inherent properties of the G·C nucleobase pairs. In this study, we have obtained intriguing results, lying far beyond the existing representations. Thus, it was shown that Löwdin's G*·C*(WC) base pair does not tautomerize according to the wobblization mechanism. Tautomeric wobblization of the G*·C*(rWC) (relative Gibbs free energy ΔG = 0.00/relative electronic energy ΔE = 0.00 kcal·mol−1) (“r”—means the configuration of the base pair in reverse position; “WC”—the classic Watson-Crick configuration) and G*t·C*(H) (ΔG = −0.19/ΔE = 0.29 kcal·mol−1) (“H”—Hoogsteen configuration;”t” denotes the O6H hydroxyl group in the trans position) base pairs are preceded by the stages of the base pairs tautomerization by the single proton transfer (SPT). It was established that the G*t·C*(rH) (ΔG = 2.21/ΔE = 2.81 kcal·mol−1) base pair can be wobbled through two different pathways via the traditional one-stage mechanism through the TSs, which are tight G+·C− ion pairs, stabilized by the participation of only two intermolecular H-bonds. It was found out that the G·C base pair is most likely incorporated into the DNA/RNA double helix with parallel strands in the G*·C*(rWC), G·C*(rwwc), and G*·C(rwwc) (“w”—wobble configuration of the pair) tautomeric forms, which are in rapid tautomeric equilibrium with each other. It was proven that the G*·C*(rWC) nucleobase pair is also in rapid tautomeric equilibrium with the eight tautomeric forms of the so-called Levitt base pair. It was revealed that a few cases of tautomerization via the DPT of the nucleobase pairs by the participation of the C8H group of the guanine had occurred. The biological role of the obtained results was also made apparent.

Межмолекулярные взаимодействия в полиамидах с участие воды

Впервые методом ИК-спектроскопии зафиксировано наличие в полиамиде-6 и в супрамоле-кулярном абсорбенте «Твердая вода» циклических структур, образованных карбоксильными группа-ми в соседних параллельных цепочках, а также лактамных фрагментов, возникающих в результате таутомерных превращений (с участием амидных групп).Установлена способность полиамидов поглощать фенол и его производные из водных рас-творов. Сорбция проявляет себя весьма эффективно, так как фенол образует с С=О-группами амид-ных группировок более прочные водородные связи, чем связи -NHCO…Н2О и OHOH2.Предложена концепция модификации в триаде взаимодействующих составляющих «вода-мицеллярный микрореактор с поверхностно активным веществом (ПАВ)-неподвижная фаза». Для суперабсорбента «Твердая вода» присуще то, что после его внесения в сухую почву и однократного полива, роль неподвижной фазы выполняет мицелла, модифицированная ПАВ. При этом поверхност-но активное вещество проявляет себя и как кристаллит, и как жидкая фаза с ламинарной структурой.Показано, что в трехкомпонентной модели главную роль играют коэффициент распределения вещества (КMW) между мицеллой и водой и коэффициент распределения вещества (КSM) между непо-движной фазой (НФ). Весьма скромная роль в рассматриваемой трёхкомпонентной модели отводится коэффициенту распределения вещества (КSW) между неподвижной фазой и водой, так как КSW на два порядка и более меньше по сравнению с КMW.Представлены данные о влиянии рН на образование мицелл амфотерными ПАВ. В кислых средах данные соединения существуют в катионной форме (рН<рI); в нейтральных средах (при рН=рI, где I – изоэлектрическая точка) в форме биполярных ионов; в средах с высокими значениями рН – в виде анионов (рН>рI). В реакциях протолиза с индикаторами они проявляют себя как инициа-торы перехода бензольных структур в хиноидные, что приводит к появлению в индикаторах цепей сопряжения (конъюгации) с чередующимися одинарными и кратными связями.Приведены данные, показывающие влияние коэффициентов распределения в подвижной (ПФ) и неподвижной (НФ) фазах в тонкослойной хроматографии на величины константы протолиза Ка разделяемых компонентов и на значение рН в мицеллярных реакторах.Авторы статьи убеждены, что полиамиды займут наряду с другими полимерами достойное место как неподвижные фазы в плоскостной хроматографии и высокоэффективной жидкостной хро-матографии.

Inhibitive and adsorption behavior of thiadiazole derivatives on carbon steel corrosion in CO2-saturated oilfield produced water: Effect of substituent group on efficiency

Three thiadiazole derivatives with different substituent groups, 2-(benzylthio)-5-methyl-1,3,4-thiadiazole(BMT), 2-(benzylthio)-5-(butylthio)-1,3,4-thiadiazole(BBT), and 5-(benzylthio)-1,3,4-thiadiazole-2-thiol(BTT), were synthesized and studied as the corrosion inhibitors for N80 carbon steel in CO2-saturated oilfield produced water. It is found that the synthesized thiadiazole derivatives could effectively inhibit the corrosion of N80 carbon steel by chemisorption. The corrosion inhibition performance of the organic compounds is in the order: BTT > BBT > BMT. The theoretical calculations indicate that the tautomeric transformation from thiol-BTT to thione-BTT may be responsible for the high inhibition performance of BTT.

Bismuth(III)-Catalyzed Sequential Enamine-Imine Tautomerism/2-Aza-Cope Rearrangement of Stable β-Enaminophosphonates: One-Pot Synthesis of β-Aminophosphonates.

A novel catalytic tautomeric transformation of a β-enaminophosphoryl and 2-aza-Cope rearrangement sequence has been successfully applied to the one-pot synthesis of β-aminophosphonates with high efficiency and good tolerance. In this tandem reaction, Bi(OTf)3 exhibits unique activities and promotes both of enamine-imine tautomerism and 2-aza-Cope rearrangement.

Circular linkage of intramolecular multi-hydrogen bonding frameworks through nucleophilic substitutions of β-dicarbonyls onto cyanuric chloride and subsequent tautomerisation.

Nucleophilic substitution reactions of cyanuric chloride with a series of β-dicarbonyls give triply β-dicarbonyl-embedded 1,3,5-triazines. Their subsequent but spontaneous tautomeric transformation leads to circularly linked, intramolecular, multi-hydrogen bonding networks. Their structural elucidation by X-ray crystallography showed elongated double bonds and shortened single bonds. This is likely due to a resonance hybrid formed via tautomerisation and simultaneous proton transfer.

Теоретическое изучение изомеризации 1-амино-4-фениламино-9,10-антрахинона

This paper presents the results of computer simulation of tautomeric transformations of the molecule 1-amino-4-phenylamino-9,10-anthraquinone. It is known from the literature that the presence of substituents in the 1,4-position of anthraquinone-9,10 leads to various tautomeric transformations, with a shift in the absorption maximum and the appearance of absorption bands in the red wave region in electronic spectra. Both the 1-amino-4-hydroxyanthraquinone described in the literature and the 1-amino-4-phenylamino-9,10-anthraquinone are characterized by two types of prototropic tautomerism – keto-enol and amino-imine. Quantum-chemical modeling contributes to the calculation of the relative energies of tautomers and isomers, the barriers of their interconversions, as well as finding their structural parameters. The aim of this study was to study the mechanism of the formation of tautomers during hydrogen transfer in the molecule of 1-amino-4-phenylamino-9,10-anthraquinone, as well as the formation of isomers during migration of the OH group. The calculations were performed using the Gaussian09 program. To study of various tautomers of 1-amino-4-phenylamino-9,10-anthraquinone, the B3LYP method with the def2TZV basis was used. A search was conducted for transition states during hydrogen transfer and OH group migration. The descent along the reaction path was calculated to confirm that the transition state is in the path of the desired reaction. The minima corresponding to the starting material and product were localized. The activation enthalpies of the studied reactions were calculated. Migration of the OH group in the 1-amino-4-phenylamino-9,10-anthraquinone molecule leads to the formation of 4-phenylamino-9-amino-1,10-anthraquinone. As the calculation shows, the keto-form of 1-amino-4-phenylamino-9,10-anthraquinone is energetically more profitable than all the isomers studied in this work, including the enol form. The smallest difference in total potential energies is 23.7 kJ/mol between the initial ketone form of 1-amino-4-phenylamino-9,10-anthraquinone and the last transformation structure – the 4-phenylamino-9-amino-1,10-anthraquinone molecule.