A comparative study on the hydrolysis of acetic anhydride and N,N‐dimethylformamide: Kinetic isotope effect,transition‐state structure,polarity, and solvent effect

Recent studies have shown that general‐base assisted catalysis is a viable mechanistic pathway for hydrolysis of smaller anhydrides. Therefore, it is the central purpose of the present work to compare and contrast the number of hydrogen atoms in‐flight and stationary in the transition state structure of the base‐catalyzed mechanisms of 2 hydrolytic reactions as well as determine if any solvent effects occur on the mechanisms. The present research focuses on the hydrolytic mechanisms of N,N‐dimethylformamide (DMF) and acetic anhydride in alkali media of varying deuterium oxide mole fractions. Acetic anhydride has been included in this study to enable comparisons with DMF hydrolysis. Comparative studies may give synergistic insight into the detailed structural features of the activated complexes for both systems. Hydrolysis reactions in varying deuterium oxide mole fractions were conducted in concentrations of 2.0M , 2.5M , and 3.0M for DMF and 0.10M for acetic anhydride at 25°C. Studies in varying deuterium mole fractions allow for proton inventory analysis, which sheds light on the number and types of hydrogen atoms involved in the activated complex. For these systems, this type of study can distinguish between direct nucleophilic attack of the hydroxide ion on the carbonyl center and general‐base catalysis by the hydroxide ion to facilitate a water molecule attacking the carbonyl center. The numerical data are used to discuss 3 possible mechanisms in the hydrolysis of DMF.     

Complex formation and proton transfer between formic acid and water adsorbed on Au(111) surfaces under UHV conditions

The coadsorption of formic acid and water on Au(111) surfaces has been investigated by means of vibrational and photoelectron spectroscopy (HREELS, XPS). Formic acid adsorbs at 90 K molecularly with vibrational modes characteristic for flat lying zig-zag chains in the mono- and multilayer regime, like in solid formic acid. Annealing results in a complete desorption at 190 K. Sequential adsorption of formic acid and water at 90 K shows no significant chemical interaction. Upon annealing the coadsorbed layer to 140 K a hydrogen-bonded cyclic complex of formic acid with one water molecule could be identified using isotopically labelled adsorbates (D₂O, H¹³COOD). Upon further annealing this complex decomposes leaving molecularly adsorbed formic acid on the surface at 160 K, accompanied by a proton exchange between formic acid and water. PACS 68.08.-p; 68.43.-h; 68.43.Pq     

Time-dependent density functional theory study on excited state intramolecular proton transfer of 3-hydroxy-2-(pyridin-2-yl)-4H-chromen-4-one

The time-dependent density functional theory (TDDFT) method was carried out to investigate the excited state intramolecular proton transfer (ESIPT) process of 3-hydroxy-2-(pyridin-2-yl)-4H-chromen-4-one (1a). 1a has two tautomeric forms: one is 1a(O), which is induced by intramolecular hydrogen bond O-H?O=C, and the other one is 1a(N), which is caused by intramolecular hydrogen bond O-H?N. From excited state to tautomer excited state coming from ESIPT, the hydroxyl hydrogen breaks away and the dissociated hydrogen adsorbed on pyridinic nitrogen or carbonyl oxygen formed new intramolecular HB and the corresponding bond length and bond angle varied greatly. In comparison, a similar process of proton transfer for 1a(N)H⁺ protonated 1a(N) from ground state to excited state was obtained. This detailed proton transfer mechanism was provided by molecular orbitals analysis and it may be applied to molecular switch and organic Lewis acid/base. We investigated the excited state proton transfer mechanism of the four molecules through the theoretical method for the first time and gave unambiguous geometry of excited state.     

The effect of benzo‐annelation on intermolecular hydrogen bond and proton transfer of 2‐methyl‐3‐hydroxy‐4(1H)‐quinolone in methanol: A TD‐DFT study

Excited‐state intermolecular or intramolecular proton transfer (ESIPT) reaction has important potential applications in biological probes. In this paper, the effect of benzo‐annelation on intermolecular hydrogen bond and proton transfer reaction of the 2‐methyl‐3‐hydroxy‐4(1H)‐quinolone (MQ) dye in methanol solvent is investigated by the density functional theory and time‐dependent density functional theory approaches. Both the primary structure parameters and infrared vibrational spectra analysis of MQ and its benzo‐analogue 2‐methyl‐3‐hydroxy‐4(1H)‐benzo‐quinolone (MBQ) show that the intermolecular hydrogen bond O₁―H₂?O₃ significantly strengthens in the excited state, whereas another intermolecular hydrogen bond O₃―H₄?O₅ weakens slightly. Simulated electron absorption and fluorescence spectra are agreement with the experimental data. The noncovalent interaction analysis displays that the intermolecular hydrogen bonds of MQ are obviously stronger than that of MBQ. Additionally, the energy profile analysis via the proton transfer reaction pathway illustrates that the ESIPT reaction of MBQ is relatively harder than that of MQ. Therefore, the effect of benzo‐annelation of the MQ dye weakens the intermolecular hydrogen bond and relatively inhibits the proton transfer reaction.     

Computational studies of the cyclization of thiosemicarbazides

While typically cyclodehydration of thiosemicarbazides in acidic media leads to 1,3,4‐thiadiazoles, we have recently shown that under reflux conditions in anhydrous acetic acid the cyclization yields an imidazolidine derivative. The mechanism of this reaction has been characterized theoretically. Calculations indicate that this direction, facilitated by the presence of the ? CH₂CO₂? moiety in the N4 substituent is favored over the direction leading toward the thiadiazole product. Formation of the C? N bond that closes the five‐member ring appears to be concerted with the departure of ethanol molecule, although the proton transfer from the nitrogen atom to oxygen atom is much more advanced in the transition state. Copyright © 2007 John Wiley & Sons, Ltd.     

Hydrogen bonding effects on the (15)N and (1)H shielding tensors in nucleic acid base pairs

The results of systematic ab initio calculations of (15)N and (1)H chemical shielding tensors in the GC base pair as a function of hydrogen bond length are presented for the first time. The hydrogen bond length characterized by the distance r(N...N) between purine N1 and pyrimidine N3 was varied between 2.57 and 3.50 A and the chemical shift tensors were calculated by the sum-over-states density functional perturbation theory. It is shown that the hydrogen bond length has a strong effect on the chemical shielding tensor of both imino proton and nitrogen, on their orientation, and, as a consequence, on the relaxation properties of both nuclei. For a nitrogen nucleus not involved in hydrogen bonding, the shielding tensor is nearly axially symmetric and almost collinear with the bond vector. As the length of the hydrogen bond decreases, the least shielding component sigma(11) deflects from the N-H vector and the shielding tensor becomes increasingly asymmetric. The significance of the presented results for the analysis of relaxation data and the efficiency of TROSY effects together with a summary of the relevant shielding parameters are presented and discussed.     

Synthesis and Spectroscopic Structural Elucidation of New Quinoxaline Derivatives

A quinoxaline‐2,3‐dione derivative was synthesized, and its chemical structure was determined through spectral analysis. Alkylation of this compound under phase transfer catalysis (PTC) conditions yielded monoalkylated and diakylated adducts. The monolalkylation process was shown to be regioselective occurring on the quinoxalic nitrogen atom rather than on its pyrazolic analogue. The full characterization of the synthesized compounds was studied by concerted use of NMR and MS techniques. Assignments of proton and carbon atoms were achieved through analysis of the 1D ¹H and ¹³C NMR spectra combined with homo‐ and hetero-nuclear 2D NMR experiments. Determination of the alkylation site was achieved through long‐range proton–carbon coupling correlations spectroscopy.     

Correlated Tunneling in Hydrogen Bonds

We study the quantum nature of the protons participating in hydrogen bonds in several ice structures by analyzing the one particle density matrix. We find that in all cases, including ice Ih, the most common form of ice, and the high pressure phases, ice VIII, VII, and X, the system is ground-state dominated. However, while the dynamics is uncorrelated in the structures with standard asymmetric hydrogen bonds, such as ice Ih and VIII, local correlations among the protons characterize ice VII and, to a lesser extent, ice X in the so-called low barrier hydrogen bond regime. The correlations appear along the path to hydrogen bond symmetrization, when quantum fluctuations delocalize the proton on the two bond sides. The correlations derive from a strong requirement for local charge neutrality that favors concerted motion along the bonds. The resulting behavior deviates substantially from mean field theory, which would predict in ice VII coherent tunneling of the proton between the two bond sides, thereby causing an ionization catastrophe. Due to the correlations, the quantum state of the proton is entangled.     

Difference between 1H NMR signals of primary amide protons as a simple spectral index of the amide intramolecular hydrogen bond strength

The effect of the intramolecular H‐bonding of the primary amide group on the spectral properties and reactivity of this group towards electrophiles has been studied in systematic rows of 1,2,5,6,7,8‐hexahydro‐7,7‐dimethyl‐2,5‐dioxo‐1‐R‐quinoline‐3‐carboxamides and 2‐aryliminocoumarin‐3‐carboxamides using ¹H and ¹⁵N NMR spectroscopy and the kinetics of model reactions. The upfield signal of the amide proton that is not intramolecularly H‐bonded (H^a) depends on external factors such as solvent nature and concentration. At the same time, the downfield chemical shift of the H^b proton (bonded by the intramolecular hydrogen bond) depends mostly on the strength of the intramolecular H‐bond, which is affected by such internal factor as electron nature of substituent R. The substituent's influence on the H^b proton's chemical shift is more effective in deuterochloroform medium than in DMSO‐d₆ where the intramolecular hydrogen bond is less stable. The value Δδ(H) = δ(H^b) ? δ(H^a) is suggested as a simple comparative spectral index of the intramolecular hydrogen bond strength in these and similar compounds. By contrast, the effect of R on the ¹⁵N NMR chemical shift of the amide nitrogen has turned out to be too small to estimate changes of the electron density at the nitrogen. The effect of the intramolecular H‐bond on the reactivity of the amide group is twofold. When the cleavage of the H‐bond occurs on the rate limiting step it dramatically reduces the reaction rate. In the other case, the strengthening of the H‐bond favors the reaction rate because of the increase of the electron density at the amide nitrogen. Copyright © 2011 John Wiley & Sons, Ltd.     

Understanding the role of Zn2+ in the hydrolysis of glycylserine: a mechanistic study by using density functional theory

The hydrolysis mechanism of glycylserine in the presence of Zn²⁺ was theoretically studied by means of density functional theory calculations. Two possible reaction mechanisms are proposed for the hydrolysis reaction: (1) the first one involves a stepwise reaction with an initial attack of the serine –OH to the amide carbonyl group through a general base catalysis of a water molecule, which undergoes to a proton transfer to the carboxylate group to give a cyclic intermediate. Its further rearrangement finally forms an ester that hydrolyses to yield products. (2) The second mechanism involves a general base catalysis by the carboxylate group for the water attack to the amide carbonyl group to generate a tetrahedral intermediate. Upon comparison of both mechanisms, it is observed that the former is favoured; furthermore, its first step is the rate-limiting step in a bicyclic asynchronous transition state with evolution of 86% in C₍₁₎–O₍₂₎ bond. The crucial role of Zn²⁺ in this hydrolysis process can be rationalised in terms of the inductive effect and the formation of a rigid structure that increases the electrophilicity of the amide carbonyl group. The calculations presented in this report are in good agreement with reported values for the activation barrier.     

Concerted motion of protons in hydrogen bonds of DNA-type molecules

We study the dynamical behavior of proton transfer in hydrogen bonds in the base pairs of double helices of the DNA type. Under the assumption that the elastic and tunnelling degrees of freedom may be coupled, we derive a nonlinear and nonlocal Schrödinger equation (NLNLS) that describes the concerted motion of the proton tunnelling. Rough estimates of the solutions to the NLNLS show an intimate interplay between the concerted tunnelling of protons and the symmetry of the double helix.     

Explanation for Hydrogen Bonds of Chitin‐Alcohols from Lewis Acid‐Base Theories

The inverse gas chromatography (IGC) method was used to characterize the hydrogen bond energies of chitin‐methanol and chitin‐ethanol. Surface Lewis acid‐base properties of the chitin were determined at the same time. Six solvents, trichloromethane, acetone, ether, tetrahydrofuran, methanol, and ethanol were used as polar probes for the IGC measuration. The hydrogen bond energies of chitin‐methanol and chitin‐ethanol were 23.3 and 21.3 kJ/mol, respectively. Because the linear relation of the plot of ?ΔH_a ^s/AN* versus DN/AN* (DN and AN* are the Gutmann's donor and modified acceptor numbers of solvents) for the six probes was perfect, it can be concluded that the hydrogen bonds of chitin‐alcohols belong to Lewis acid‐base interactions. The hydrogen bonds were moderate hydrogen bonds.     

Electron energy loss spectroscopy of the decomposition of formic acid on Ru(001)

Electron energy loss spectroscopy has demonstrated the existence of both a monodentate and a symmetric bidentate bridging formate as stable intermediates in the decomposition of formic acid on the Ru(001) surface. The monodentate formate converts upon heating to the bidentate formate which decomposes via two pathways: CH bond cleavage to yield CO₂ and adsorbed hydrogen; and CO bond cleavage to yield adsorbed hydrogen, oxygen and CO. Thermal desorption spectra demonstrate the evolution of H₂,H₂O, CO and CO₂ as gaseous products of the decomposition reaction. The observation of this product distribution from Ru(100), Ni(100) and Ni(110) had prompted the proposal of a formic anhydride intermediate, the existence of which is rendered questionable by the spectroscopic results reported here.     

A DFT study on the structure and radical scavenging activity of newly synthesized hydroxychalcones

Quantum‐chemical computations based on the density functional theory have been employed to study the relation between the structure and the radical scavenging activity of six newly synthesized hydroxychalcones. The three main working mechanisms, hydrogen atom transfer (HAT), stepwise electron‐transfer‐proton‐transfer, and sequential‐proton‐loss‐electron‐transfer (SPLET), were investigated, and the O–H bond dissociation enthalpy, ionization potential, proton dissociation enthalpy, and electron transfer energy parameters were computed in the gas phase and in solvents using PCM model. The geometry structure, radical, electron character, and the frontier molecular orbital were analyzed to explore the key factors that influence the radical scavenging activity of the hydroxychalcones. Results indicated that 3,4‐dihydroxychalcone (6) possessing the catechol functionality is expected to be more efficient hydrogen atom and proton donor than others. The theoretical results confirm the important role of the B‐ring and shed light on the role of the o‐dihydroxy (catechol) moiety in the antioxidant properties of hydroxychalcones. In addition, the calculated results are in good agreement with experimental values. It was found that HAT is the most favored mechanism for explaining the radical‐scavenger activity of hydroxychalcone in the gas phase, whereas SPLET mechanism is thermodynamically preferred pathway in aqueous solutions. Copyright © 2012 John Wiley & Sons, Ltd.     

The antioxidant activity of 4‐hydroxycoumarin derivatives and some sulfured analogs

In this work, the relationship between the structure and the radical scavenging activity of seven hydroxycoumarins and their sulfured analogs was investigated for the first time by density functional theory calculation in the gas phase, benzene, and water. Our investigation includes hydrogen atom transfer, single‐electron transfer–proton transfer, and sequential proton loss electron transfer mechanisms. The results revealed that the bond dissociation enthalpy values of sulfured coumarins were lower than those of hydroxylated analogs. The obtained results were in a good agreement with the experimental results. The hydrogen atom transfer mechanism is dominant in both benzene and vacuum. The sequential proton loss electron transfer mechanism represents the most thermodynamically preferred reaction pathway in water. However, single‐electron transfer–proton transfer mechanism is not the most preferred one in all media. Finally, this work contributes to the understanding of the pharmacological activity of the compounds studied. Copyright © 2015 John Wiley & Sons, Ltd.     

Theoretical study of the smiles rearrangement in the activation mechanism of proton pump inhibitors

This work describes the conformational behavior and the activation mechanism of timoprazole and substituted prazoles from the most stable conformation to the sulphenic acid. The stability of the conformers can be explained by the presence of hydrogen bonds, stereoelectronic effect because of the lone pair of sulfur atom and the N^…C and N^…S interactions. The first step of the Smile rearrangement is a nucleophilic addition to benzimidazole by pyridine moiety, which depends on the difference of the electron population of the atoms involved in the attack. The second step produces sulphenic acid by a concerted reaction where breaking of the S–C bond goes along with a proton migration, and is determined by the electron population of the sulfur atom. Copyright © 2011 John Wiley & Sons, Ltd.     

铵水间质子交换的再研究:不受扩散约束的化学交换

对铵盐水溶液中铵离子与水分子间的质子交换进行了再研究. 以核磁共振(NMR) 波谱学方法测定了不同pH值, 不同温度和含不同共存盐浓度的氯化铵水溶液中质子交换速率, 组分自扩散系数及NMR自旋晶格弛豫时间. 结果显示铵水间的质子交换并不受交换主体分子或离子自扩散的约束. 交换机理包括化学键和氢键的交换. 在溶液中, 水分子以氢键为桥 梁连接铵和其因水解而产生的碱性部分--氨. 在氢交换的过程中, 氨从水分子接受一个氢 成为铵, 同时另外一端的铵提供一个氢给水分子而变成氨, 或者一个氢从水分子转移到氨而同 时另外一个氢从铵转移到水. 在铵水质子交换的过程中没有净的电荷转移. 在低pH条件下, 由水解产生的氨的浓度降低, 亦即铵-水-氨复合物减少, 结果氢交换的可能性降低. 这解释了生物氢交换体系中的一种常见的在低pH值条件下氢交换变慢的现象.     

Theoretical investigation on the excited‐state intramolecular proton transfer mechanism of 2‐(2′‐benzofuryl)‐3‐hydroxychromone

Spectroscopic studies on excited‐state proton transfer of a new chromophore 2‐(2′‐benzofuryl)‐3‐hydroxychromone (BFHC) have been reported recently. In the present work, based on the time‐dependent density functional theory (TD‐DFT), the excited‐state intramolecular proton transfer (ESIPT) of BFHC is investigated theoretically. The calculated primary bond lengths and angles involved in hydrogen bond demonstrate that the intramolecular hydrogen bond is strengthened. In addition, the phenomenon of hydrogen bond reinforce has also been testified based on infrared (IR) vibrational spectra as well as the calculated hydrogen bonding energies. Further, hydrogen bonding strengthening manifests the tendency of excited state proton transfer. Our calculated results reproduced absorbance and fluorescence emission spectra of experiment, which verifies that the TD‐DFT theory we used is reasonable and effective. The calculated Frontier Molecular Orbitals (MOs) further demonstrate that the excited state proton transfer is likely to occur. According to the calculated results of potential energy curves along O―H coordinate, the potential energy barrier of about 14.5 kcal/mol is discovered in the S₀ state. However, a lower potential energy barrier of 5.4 kcal/mol is found in the S₁ state, which demonstrates that the proton transfer process is more likely to happen in the S₁ state than the S₀ state. In other words, the proton transfer reaction can be facilitated based on the photo‐excitation effectively. Moreover, the phenomenon of fluorescence quenching could be explained based on the ESIPT mechanism. Copyright © 2015 John Wiley & Sons, Ltd.     

A detailed DFT/TDDFT study on excited‐state intramolecular hydrogen bonding dynamics and proton‐transfer mechanism of 2‐phenanthro[9,10‐d]oxazol‐2‐yl‐phenol

In this present work, using density functional theory and time‐dependent density functional theory methods, we theoretically study the excited‐state hydrogen bonding dynamics and the excited state intramolecular proton transfer mechanism of a new 2‐phenanthro[9,10‐d]oxazol‐2‐yl‐phenol (2PYP) system. Via exploring the reduced density gradient versus sign(λ₂(r))ρ(r), we affirm that the intramolecular hydrogen bond O1‐H2?N3 is formed in the ground state. Based on photoexcitation, comparing bond lengths, bond angles, and infrared vibrational spectra involved in hydrogen bond, we confirm that the hydrogen bond O1‐H2?N3 of 2PYP should be strengthened in the S₁ state. Analyses about frontier molecular orbitals prove that charge redistribution of 2PYP facilitates excited state intramolecular proton transfer process. Via constructing potential energy curves and searching transition state structure, we clarify the excited state intramolecular proton transfer mechanism of 2PYP in detail, which may make contributions for the applications of such kinds of system in future.