Theoretical estimates of the IR spectrum of formamide intercalated into kaolinite

Calculations at PM3 and PBE/6‐31G levels of part of the IR spectrum of the formamide‐kaolinite intercalatation compound based on a 110‐atom cluster of kaolinite with one formamide molecule are reported. Frequencies and intensities for the formamide vibrations and stretchings of four cluster hydroxyls were calculated through partial hessian matrices and polar tensors obtained by numerical differentiation of energy gradients and dipole moment. The formamide molecule attaches to the kaolinite inner surfaces in multiple conformations with its CN bond vector parallel to the surfaces. Hydrogen bonds are formed between the formamide hydrogen atoms (both from NH₂ or CH groups) and the siloxane surface and between the formamide oxygen and nitrogen atoms and the aluminol hydroxyls. The general features of the experimental assignment of the spectrum are confirmed, but the observed splitting of formamide bands is attributed to vibrations from differently attached molecules. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Microsolvation of formamide: a rotational study

Microsolvated formamide clusters have been generated in a supersonic jet expansion and characterized using Fourier transform microwave spectroscopy. Three conformers of the monohydrated cluster and one of the dihydrated complex have been observed. Seven monosubstituted isotopic species have been measured for the most stable conformer of formamide...H(2)O, which adopts a closed planar ring structure stabilized by two intermolecular hydrogen bonds (N-H...O(H)-H...O=C). The two higher energy forms of formamide...H(2)O have been observed for the first time. The second most stable conformer is stabilized by a O-H...O=C and a weak C-H...O hydrogen bond, while, in the less stable form, water accepts a hydrogen bond from the anti hydrogen of the amino group. For formamide...(H(2)O)(2), the parent and nine monosubstituted isotopic species have been observed. In this cluster the two water molecules close a cycle with the amide group through three intermolecular hydrogen bonds (N-H...O(H)-H...O(H)-H...O=C), the nonbonded hydrogen atoms of water adopting an up-down configuration. Substitution (r(s)) and effective (r(0)) structures have been determined for formamide, the most stable form of formamide...H(2)O and formamide...(H(2)O)(2). The results on monohydrated formamide clusters can help to explain the observed preferences of bound water in proteins. Clear evidence of sigma-bond cooperativity effects emerges when comparing the structures of the mono- and dihydrated formamide clusters. No detectable structural changes due to pi-bond cooperativity are observed on formamide upon hydration.     

溶剂分子对甲酰胺及其衍生物分子内氢转移催化作用的研究

在B3LYP/6-311+ +G* * 水平下,通过计算所形成二元团簇的能量来研究水、氨、甲醇、氟化氢等溶剂分子对甲酰胺及其衍生物分子内氢原子转移的催化作用.简单描绘了在有水、氨、甲醇和氟化氢等溶剂分子存在时,甲酰胺及其衍生物分子内氢原子转移的过程.结果表明,当有水、氨、甲醇、氟化氢等溶剂分子存在时,从甲酰胺甲酰胺酸转变的能垒会降低.而且不同的溶剂分子对甲酰胺(FA)、 N-甲基甲酰胺(MF)和N,N-二甲基甲酰胺(DMF)的催化能力各不相同.在这四种溶剂分子中,氟化氢的催化作用最强.     

A theoretical study on the mechanism of the reductive half-reaction of xanthine oxidase

On the basis of the crystal structure of an aldehyde oxidoreductase, Huber et al. proposed a catalytic mechanism for the reductive half-reaction of xanthine oxidase which involves nucleophilic addition of Mo-bound hydroxide (Moco 1) to the substrate and hydride transfer from the substrate to sulfido group (Mo=S). Density functional theory calculations have been carried out for the oxidation of formaldehyde, acetaldehyde, formamide, and formamidine with Moco 2 to understand more detailed catalytic pathways. Our calculation results indicate that the anionic catalyst model acts as a nucleophile and is reactive for the oxidation of aldehyde substrates, which are reactive for nucleophilic addition. In these cases, a concerted mechanism is found to be more favorable than a stepwise mechanism. The concerted mechanism is further shown to be promoted by the presence of a nearby water molecule, in the active site, which serves as a Lewis acid for the nucleophilic addition of hydroxide. For less reactive formamide and formamidine (a model for xanthine) substrates, the calculated activation energies with the above mechanisms are high. These reactions also do not benefit from the presence of the water molecule. The results indicate that different catalyst forms might be responsible for the oxidation of different substrates, which could be regulated by the enzyme active site environment.     

Probing the acidity of p-substituted phenols in the excited state: electronic spectroscopy of the p-cyanophenol-water cluster.

The hydrogen bond structure of the p-cyanophenol-water cluster has been determined in the ground and first excited electronic state by rotationally resolved UV spectroscopy. The water molecule is trans-linearly bound to the hydroxy group of the p-cyanophenol moiety, with hydrogen bond distances considerably shorter in both electronic states than in the similar phenol-water cluster. The structure of the cluster has been elucidated by ab initio calculations at various levels of theory and compared to the experimental findings. The barriers to internal rotation of the water moiety were determined experimentally to be 275 and 183 cm(-1) for the ground and excited state, respectively. Hydrogen bond distances and the energy barrier to water torsion correlate with the pK(a) values of different substituted phenols for both electronic states.     

Anionotropic rearrangement in a series of derivatives of teucrin A

Under the action of catalytic amounts of mineral acid, the pentaol obtained by the reduction of the norditerpenoid teucrin A with lithium tetrahydroaluminate undergoes an anionotropic rearrangement with the subsequent elimination of a molecule of water.     

Synthesis of models of metabolites: Oxidation of variously substituted chromenes including acronycine,by a porphyrin catalytic system

The influence of chemical neighbouring on oxidation of substituted 2,2‐dimethylchromenes derivatives 5‐8 by a biomimetic catalytic system was first studied. It was then applied to acronycine an anti‐cancer drug in order to obtain in one single step oxidized products resulting from the reactivity of the 1,2‐double bond in the pyranic D‐ring. These 2,2‐dimethylchromenes constitute the structural moiety responsible for the activity of acronycine. This oxidation showed the sensitivity of the ethylenic bond, leading to the formation of the corresponding epoxides, diols and/or ketoalcohol. In the case of 5‐dimethylamino‐2,2‐dimethylchromene 8 , the double bond was not sensitive to oxidation, but the N‐methyl groups reacted to lead to the formamide derivative 16 and an imino‐alcohol 17 . This methodology applied to acronycine molecule 1 , allowed to obtain in one step, two oxidized compounds, a trans‐diol 3 and a ketoalcohol 4 under preparative conditions.     

MO-Studies of enzyme reaction mechanisms. I. Model molecular orbital study of the cleavage of peptides by carboxypeptidase A

Ab initio and semiempiridal (AM1) molecular orbital theory has been used to model the cleavage of formamide at the active site of carboxypeptidase A. The model active site consists of a zinc dication coordinated to two imidazoles, an acetate, a water with a hydrogen-bonded formate, and a formamide molecule as model substrate. AM1 has been compared with ab initio theory for the coordination of water and formamide to Zn⁺⁺ and found to give excellent energetic results. The course of the amide cleavage was therefore calculated with AM1. The first step of the reaction is the dissociation of the zinc-coordinated water to give an active ZnOH⁺ species. The remote formate acts as proton acceptor. This process has an activation energy of only 4.6 kcal mol^?1. The next and rate-determining step is the concerted addition of the ZnOH⁺ moiety to the formamide C?O bond. The Zn? O distance in the transition state is more than 3 Å. In four further steps, the amide nitrogen is protonated and the C? N bond cleaved. The net activation energy for the entire process is 15.5 kcal mol^?1 relative to the active site model and 19.6 kcal mol^?1 relative to the most stable point on the calculated reaction profile.     

Computational study of formamide–water complexes using the SAPT and AIM methods

In this work, the complexes formed between formamide and water were studied by means of the SAPT and AIM methods. Complexation leads to significant alterations in the geometries and electronic structure of formamide. Intermolecular interactions in the complexes are intense, especially in the cases where the solvent interacts with the carbonyl and amide groups simultaneously. In the transition states, the interaction between the water molecule and the lone pair on the amide nitrogen is also important. In all the complexes studied herein, the electrostatic interactions between formamide and water are the main attractive force, and their contribution may be five times as large as the corresponding contribution from dispersion, and twice as large as the contribution from induction. However, an increase in the resonance of planar formamide with the successive addition of water molecules may suggest that the hydrogen bonds taking place between formamide and water have some covalent character.     

Can the four-coordinated, penta-valent oxygen in hydroxide water clusters be detected through experimental vibrational spectroscopy?

In this study, we construct the hydroxide water cluster, OH-(H2O)6, that (a) could support a stable hydroxide ion with a four-coordinated (pentavalent) hydroxide oxygen and (b) displays hydroxide ion migration. We study the energetic stability and dynamical evolution of the system at different internal temperatures and analyze the corresponding "dynamically averaged" vibrational density of states to discuss the conditions under which the pentavalent oxygen may be observed using vibrational action spectroscopy. We also provide an alternate hydroxide migration mechanism.     

Reactions associated with ionization in water: a direct ab initio dynamics study of ionization in (H2O)17

Quasiclassical ab initio simulations of the ionization dynamics in a (H(2)O)(17) cluster, the first water cluster that includes a fourfold coordinated (internally solvated) water molecule, have been carried out to obtain a detailed picture of the elementary processes and energy redistribution induced by ionization in a model of aqueous water. General features observable from the simulations are the following: (i) well within 100 fs following the ionization, one or more proton transfers are seen to take place from the "ionized molecule" to neighboring molecules and beyond, forming a hydronium ion and a hydroxyl radical; (ii) two water molecules close to the ionized water molecule play an important role in the reaction, in what we term a "reactive trimer." The reaction time is gated by the encounter of the ionized water molecule with these two neighboring molecules, and this occurs anytime between 10 and 50 fs after the ionization. The distances of approach between the ionized molecule and the neighboring molecules indeed display best the time characteristics of the transfer of a proton, and thus of the formation of a hydronium ion and a OH radical. These findings are consistent with those for smaller cyclic clusters, albeit the dynamics of the proton transfer displays more varieties in the larger cluster than in the small cyclic clusters. We used a partitioning scheme for the kinetic energy in the (H(2)O)(17) system that distinguishes between the reactive trimer and the surrounding "medium." The analysis of the simulations indicates that the kinetic energy of the surrounding medium increases markedly right after the event of ionization, a manifestation of the local heating of the medium. The increase in kinetic energy is consistent with a reorganization of the surrounding medium, electrostatically forced in a very short time by the water cation and in a longer time by the formation of the hydronium ion.     

Formamide tautomerization: catalytic role of formic acid

Formic acid catalyzed tautomeric conversion of formamide to formamidic acid has been investigated by use of ab initio and density functional theoretical calculations. In a 1:1 dimeric complex between formamide and formic acid, the tautomeric conversion occurs via double-hydrogen transfer within an eight-member hydrogen-bonded cyclic network. The results predict that the energy barrier of the catalytic process is reduced by more than a factor of 4 compared to that in the isolated formamide molecule in the gas phase, and the tautomerization in the 1:1 complex is several kcal/mol less endothermic than that of the isolated molecule. The potential energy surface corresponding to this double hydrogen transfer process indicates that a concerted transfer of both the hydrogen atoms along the hydrogen bond directions is energetically favorable, and no minimum for an ionic intermediate, which may arise for stepwise transfer, was predicted. The unique configuration of the transition state has been identified by starting the reaction from both the tautomeric forms, and the transition state was subjected to IRC calculation.     

Investigating the hydrogen-bond acceptor site of the nicotinic pharmacophore model: a computational and experimental study using epibatidine-related molecular probes

The binding mode of nicotinic agonists has been thoroughly investigated in the last decades. It is now accepted that the charged amino group is bound by a cation-π interaction to a conserved tryptophan residue, and that the aromatic moiety is projected into a hydrophobic pocket deeply located inside the binding cleft. A hydrogen bond donor/acceptor, maybe a water molecule solvating this receptor subsite, contributes to further stabilize the nicotinic ligands. The position of this water molecule has been established by several X-ray structures of the acetylcholine-binding protein. In this study, we computationally analyzed the role of this water molecule as a putative hydrogen bond donor/acceptor moiety in the agonist binding site of the three most relevant heteromeric (α4β2, α3β4) and homomeric (α7) neuronal nicotinic acetylcholine receptor (nAChR) subtypes. Our theoretical investigation made use of epibatidine 1 and deschloroepibatidine 2 as molecular probes, and was then extended to their analogues 3 and 4, which were subsequently synthesized and tested at the three target receptor subtypes. Although the pharmacological data for the new ligands 3 and 4 indicated a reduction of the affinity at the studied nAChRs with respect to reference agonists, a variation of the selectivity profile was clearly evidenced.     

The spectroscopic signature of the "all-surface" to "internally solvated" structural transition in water clusters in the n = 17-21 size regime

The existence of a transitional size regime where preferential stabilization alternates between "all-surface" (all atoms on the surface of a cluster) and "internally solvated" (one water molecule at the center of the cluster, fully solvated) configurations with the addition or the removal of a single water molecule, predicted earlier with the flexible, polarizable (many-body) Thole-type model interaction potential (TTM2-F), has been confirmed from electronic structure calculations for (H2O)n, n = 17-21. The onset of the appearance of the first "interior" configuration in water clusters occurs for n = 17. The observed structural alternation between interior (n = 17, 19, 21) and all-surface (n = 18, 20) global minima in the n = 17-21 cluster regime is accompanied by a corresponding spectroscopic signature, namely, the undulation in the position of the most redshifted OH stretching vibrations according to the trend: interior configurations exhibit more redshifted OH stretching vibrations than all-surface ones. These most redshifted OH stretching vibrations form distinct groups in the intramolecular region of the spectra and correspond to localized vibrations of donor OH stretches that are connected to neighbors via "strong" (water dimer-like) hydrogen bonds and belong to a water molecule with a "free" OH stretch.     

Binding and catalytic behavior of modified γ-cyclodextrins

Modified -cyclodextrins appended by an aromatic moiety show unique binding behavior, including a guest molecule together with the appended moiety in their -cyclodextrin cavities. Excimer formation, photoresponsive binding, association with -cyclodextrin and enhanced catalytic activity have been explained on this basis.     

Interaction energy of a water molecule with a single-layer graphitic surface modeled by hydrogen- and fluorine-terminated clusters

In ab initio calculations a finite graphitic cluster model is often used to approximate the interaction energy of a water molecule with an infinite single-layer graphitic surface (graphene). In previous studies, the graphitic cluster model is a collection of fused benzene rings terminated by hydrogen atoms. In this study, the effect of using fluorine instead of hydrogen atoms for terminating the cluster model is examined to clarify the role of the boundary. The interaction energy of a water molecule with the graphitic cluster was computed using ab initio methods at the MP2 level of theory and with the 6-31G(d = 0.25) basis set. The interaction energy of a water molecule with graphene is estimated by extrapolation of two series of increasing size graphitic cluster models (C(6n2)H(6n) and C(6n2)F(6n), n = 1-3). Two fixed orientations of water molecule are considered: (a) both hydrogen atoms of water pointing toward the cluster (mode A) and (b) both hydrogen atoms of water pointing away from the cluster (mode B). The interaction energies for water mode A are found to be -2.39 and -2.49 kcal/mol for C(6n2)H(6n) and C(6n2)F(6n) cluster models, respectively. For water mode B, the interaction energies are -2.32 and -2.44 kcal/mol for C(6n2)H(6n) and C(6n2)F(6n) cluster models, respectively.     

Electron attachment to molecules in a cluster environment

Low-energy dissociative electron attachment (DEA) to the CF(2)Cl(2) and CF(3)Cl molecules in a water cluster environment is investigated theoretically. Calculations are performed for the water trimer and water hexamer. It is shown that the DEA cross section is strongly enhanced when the attaching molecule is embedded in a water cluster, and that this cross section grows as the number of water molecules in the cluster increases. This growth is explained by a trapping effect that is due to multiple scattering by water molecules while the electron is trapped in the cluster environment. The trapping increases the resonance lifetime and the negative ion survival probability. This confirms qualitatively existing experiments on electron attachment to the CF(2)Cl(2) molecule placed on the surface of H(2)O ice. The DEA cross sections are shown to be very sensitive to the position of the attaching molecule within the cluster and the orientation of the electron beam relative to the cluster.     

Enthalpy of solution of α-cyclodextrin in water and in formamide at 298.15 K

A new dissolution microcalorimeter that can measure enthalpies of dissolution of slightly soluble solids was developed by Ingemar Wadsö at Lund University, and the prototype as well as the commercial vessel were tested in our laboratory. Recently we did report the testing of the prototype and we are now extending the previous investigation to measurements with an organic solvent in the commercial vessel. The instrument performance was found to be as good with formamide as with water.The vessel was calibrated chemically (dissolution of KCl in water) and electrically, by means of a permanent and an insertion heater. The results obtained from the three methods are compared and discussed.The enthalpy of dissolution of α-cyclodextrin, dry and hydrated with six water molecules, was determined in water and in formamide. The results are discussed in terms of the difference between water and formamide as regarding dissolution and binding to the cyclodextrin molecule.     

Synthesis of 1-lyso-2-palmitoyl-rac-glycero-3-phosphocholine and its regioisomers and structural elucidation by NMR spectroscopy and FAB tandem mass spectrometry

Three regioisomers of a naturally occurring lysophosphatidylcholine were chemically synthesized from glycerol. The phosphocholine moiety of the molecule was introduced by sequentially reacting with ethylene chlorophosphite, bromine, water, and trimethyl amine. Removal of a silyl protecting group of the hydroxyl group in the glycerol backbone was achieved without any accompanying acyl migration in the final stage of the synthesis by using NBS in a dimethyl sulfoxide-water cosolvent system. Structures of all regioisomers were compared by NMR spectroscopy and FAB tandem mass spectrometry.