Rapid Prediction of the Hydrogen Bond Cooperativity in N‐methylacetamide Chains

A method is proposed to rapidly predict the hydrogen bond cooperativity in N‐methylacetamide chains. The parameters needed are obtained from the fittings to the hydrogen bonding energies in the formamide chains containing 2 to 8 monomeric units. The scheme is then used to calculate the individual hydrogen bonding energies in N‐methylacetamide chains containing 2 to 7 monomeric units. The cooperativity predicted is in good agreement with those obtained from MP2/6‐31+G** calculations by including the BSSE correction. Our scheme is further employed to predict the individual hydrogen bonding energies in larger N‐methylacetamide chains containing up to 200 monomeric N‐methylacetamide units, to which the MP2 method cannot be applied. Based on our scheme, a cooperative effect of over 170 % of the dimer hydrogen bonding energy in long N‐methylacetamide chains is predicted. The method is also applied to heterogeneous chains containing formamide, acetamide, N‐methylformamide, and N‐methylacetamide. The individual hydrogen bonding energies in these heterogeneous chains are also in good agreement with those obtained from MP2 calculations with the BSSE correction, further demonstrating that our method is reasonable.     

Hydrogen‐bond‐assisted syndiotactic‐specific radical polymerizations of N‐alkylacrylamides: The effect of the N‐substituents on the stereospecificities and unusual large hysteresis in the phase‐transition behavior of aqueous solution of syndiotactic poly(N‐n‐propylacrylamide)

The radical polymerizations of N‐alkylacrylamides, such as N‐methyl‐(NMAAm), N‐n‐propyl‐(NNPAAm), N‐benzyl‐(NBnAAm), and N‐(1‐phenylethyl)acrylamides (NPhEAAm), at low temperatures were investigated in the absence or presence of hexamethylphosphoramide (HMPA) and 3‐methyl‐3‐pentanol (3Me3PenOH), which induced the syndiotactic specificities in the radical polymerization of N‐isopropylacrylamide (NIPAAm). In the absence of the syndiotactic‐specificity inducers, the syndiotacticities of the obtained polymers gradually increased as the bulkiness of the N‐substituents increased. Both HMPA and 3Me3PenOH induced the syndiotactic specificities in the NNPAAm polymerizations as well as in the NIPAAm polymerizations. The addition of 3Me3PenOH into the polymerizations of NMAAm significantly induced the syndiotactic specificities, whereas the tacticities of the obtained polymers were hardly affected by adding HMPA. In the polymerizations of bulkier monomers, such as NBnAAm and NPhEAAm, HMPA worked as the syndiotactic specificity inducer at higher temperatures, whereas 3Me3PenOH hardly influenced the stereospecificity, regardless of the temperatures. The phase‐transition behaviors of the aqueous solutions of poly(NNPAAm)s were also investigated. It appeared that the poly (NNPAAm) with racemo dyad content of 70% exhibited unusual large hysteresis between the heating and cooling processes. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4575–4583, 2008     

Syndiotactic‐specific radical polymerization of N,N‐dimethylacrylamide in the presence of tartrates: A proposed mechanism for the polymerization

Radical polymerization of N,N‐dimethylacrylamide (DMAAm) was investigated in the presence of tartrates, such as diethyl L ‐tartrate, diisopropyl L ‐tartrate, and di‐n‐butyl L ‐tartrate, in toluene at low temperatures. Syndiotactic polymers were obtained in the presence of tartrates, whereas isotactic polymers were obtained in the absence of tartrates. The syndiotactic‐specificity increased with increasing amount of tartrates and with decreasing polymerization temperature. NMR analysis suggested that DMAAm and tartrates formed a 1:1 complex through double hydrogen bonding. A mechanism for the syndiotactic‐specific radical polymerization of DMAAm is proposed. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1192–1203, 2009     

Evaluation of the origin of conformational and tautomeric preferences in N‐formylformamide – A quantum chemical study

Quantum chemical study of N‐formylformamide (NFF) was carried out at various theoretical levels and the determinate equilibrium conformations were recomputed at the high level ab initio methods such as G2MP2, G2, G3, and complete basis set (CBS)‐QB3. The computational results reveal that the amide resonance and intramolecular hydrogen bonding are two superior factors in determining the most stable conformation of diamide (DA) and amide–imidic (AI) acid tautomers, respectively. The evaluation of hydrogen bond energies predicts that the hydrogen bond (HB( strength of NFF is weaker than the malonaldehyde (MA). But the results of atoms in molecules (AIM(, natural bond orbital (NBO), and geometrical parameters are given a different order, E_HB(NFF) > E_HB(MA). Although the bond average energies of tautomerization process emphasized on more stability of AI tautomer, but our theoretical calculations reveal that the DA conformers are more stable than the AI ones. The population analyses of equilibrium conformations by NBO method also predict that the origin of tautomeric preference is mainly because of the electron delocalization of amide functional group, especially LP(N)→ π*_C?O charge transfer. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Cooperative influence of water binding to peptides by N?H···OH2 and CO···HOH hydrogen bonds: Study by Ab Initio calculations

In this article, the geometry structures of hydrogen bond chains of formamide and N‐methylacetamide and their hydrogen‐bonded complexes with water were optimized at the MP2/6‐31G* level. Then, we performed Møller–Plesset perturbation method with 6‐311++g**, aug‐cc‐pvtz basis sets to study the cooperative influence to the total hydrogen bond energy by the N? H ··· OH₂ and C?O ··· HOH hydrogen bonds. On the basis of our results, we found that the cooperativity of the hydrogen‐bonded complexes become weaker as N? H ··· OH₂ and C?O ··· HOH hydrogen bonds replacing N? H ··· O?C hydrogen bonds in protein and peptide. It means that the N? H and C?O bonds in peptide prefer to form N? H ··· O?C hydrogen bond rather than to form C?O ··· HOH and N? H ··· OH₂. It is significant for understanding the structures and properties of the helical or sheet structures of protein and peptide in biological systems. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Anilinic N‐Oxides Support Cytochrome P450‐Mediated N‐Dealkylation through Hydrogen‐Atom Transfer

The mechanism of N‐dealkylation mediated by cytochrome P450 (P450) has long been studied and argued as either a single electron transfer (SET) or a hydrogen atom transfer (HAT) from the amine to the oxidant of the P450, the reputed iron–oxene. In our study, tertiary anilinic N‐oxides were used as oxygen surrogates to directly generate a P450‐mediated oxidant that is capable of N‐dealkylating the dimethylaniline derived from oxygen donation. These surrogates were employed to probe the generated reactive oxygen species and the subsequent mechanism of N‐dealkylation to distinguish between the HAT and SET mechanisms. In addition to the expected N‐demethylation of the product aniline, 2,3,4,5,6‐pentafluoro‐N,N‐dimethylaniline N‐oxide (PFDMAO) was found to be capable of N‐dealkylating both N,N‐dimethylaniline (DMA) and N‐cyclopropyl‐N‐methylaniline (CPMA). Rate comparisons of the N‐demethylation of DMA supported by PFDMAO show a 27‐fold faster rate than when supported by N,N‐dimethylaniline N‐oxide (DMAO). Whereas intermolecular kinetic isotope effects were masked, intramolecular measurements showed values reflective of those seen previously in DMAO‐ and the native NADPH/O₂‐supported systems (2.33 and 2.8 for the N‐demethylation of PFDMA and DMA from the PFDMAO system, respectively). PFDMAO‐supported N‐dealkylation of CPMA led to the ring‐intact product N‐cyclopropylaniline (CPA), similar to that seen with the native system. The formation of CPA argues against a SET mechanism in favor of a P450‐like HAT mechanism. We suggest that the similarity of KIEs, in addition to the formation of the ring‐intact CPA, argues for a similar mechanism of Compound I (Cpd I) formation followed by HAT for N‐dealkylation by the native and N‐oxide‐supported systems and demonstrate the ability of the N‐oxide‐generated oxidant to act as an accurate mimic of the native P450 oxidant.     

Ab initio studies of the conformers and conformational distribution of gas‐phase N,N‐dimethylaminopropanol

Systematic and extensive conformational search has been performed to characterize the gas‐phase N,N‐dimethylaminopropanol structures. A total of 91 unique trail structures were generated by allowing for all the single‐bond rotamers. All the trial structures were initially optimized at the AM1 level, and the resulting structures were optimized at the B3LYP/6‐311G* level of theory and then subjected to further optimization at the B3LYP/6‐311++G**. A total of 36 conformers are found and their zero‐point vibrational enegies, rotational constants, and dipole moments are determined. Vertical ionization energies of 11 low‐lying conformers predicted with the electron propagator theory are in good agreement with the experimental data. The two most stable conformers display intramolecular H bonds (HBs): OH···N. These HBs influence on the molecular electronic structures is exhibited by natural bond orbital analyses. Combined with statistical mechanics principles, conformational distributions at various temperatures are computed and the temperature dependence of photoelectron spectra is interpreted. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Molecular dynamics of cis‐1‐(2‐hydroxy‐5‐ methylphenyl)ethanone oxime and N‐(2‐hydroxy‐4‐methylphenyl)acetamide in solution studied by NMR spectroscopy

The formation of hydrogen bonds and molecular dynamics for the molecules cis‐1‐(2‐hydroxy‐5‐methylphenyl)ethanone oxime ( I ) and N‐(2‐hydroxy‐4‐methylphenyl)acetamide ( II ) have been investigated in solution using NMR. The results confirm the formation of O? H···O, O? H···N and O···H? N type inter‐ and intramolecular hydrogen bonds. Spin‐lattice relaxation times (T₁), activation energy of molecular dynamics and energy of intramolecular hydrogen bonds have been determined. Copyright © 2010 John Wiley & Sons, Ltd.     

A valence bond model for aqueous Cu(II) and Zn(II) ions in the AMOEBA polarizable force field

A general molecular mechanics (MM) model for treating aqueous Cu²⁺ and Zn²⁺ ions was developed based on valence bond (VB) theory and incorporated into the atomic multipole optimized energetics for biomolecular applications (AMOEBA) polarizable force field. Parameters were obtained by fitting MM energies to that computed by ab initio methods for gas‐phase tetra‐ and hexa‐aqua metal complexes. Molecular dynamics (MD) simulations using the proposed AMOEBA‐VB model were performed for each transition metal ion in aqueous solution, and solvent coordination was evaluated. Results show that the AMOEBA‐VB model generates the correct square‐planar geometry for gas‐phase tetra‐aqua Cu²⁺ complex and improves the accuracy of MM model energetics for a number of ligation geometries when compared to quantum mechanical (QM) computations. On the other hand, both AMOEBA and AMOEBA‐VB generate results for Zn²⁺–water complexes in good agreement with QM calculations. Analyses of the MD trajectories revealed a six‐coordination first solvation shell for both Cu²⁺ and Zn²⁺ ions in aqueous solution, with ligation geometries falling in the range reported by previous studies. © 2012 Wiley Periodicals, Inc.     

Hydrogen‐bond‐assisted stereocontrol in the radical polymerization of N‐isopropylacrylamide with secondary alkyl phosphate: The effect of the bulkiness of the ester group

The radical polymerization of N‐isopropylacrylamide (NIPAAm) in toluene at low temperatures was investigated in the presence of triisopropyl phosphate (TiPP). The addition of TiPP induced a syndiotactic specificity that was enhanced by the polymerization temperature being lowered, whereas atactic polymers were obtained in the absence of TiPP, regardless of the temperature. Syndiotactic‐rich poly(NIPAAm) with a racemo dyad content of 65% was obtained at ?60 °C with a fourfold amount of TiPP, but almost atactic poly(NIPAAm)s were obtained by the temperature being lowered to ?80 °C. This result contrasted with the result in the presence of primary alkyl phosphates, such as tri‐n‐propyl phosphate: the stereospecificity varied from syndiotactic to isotactic as the polymerization temperature was lowered. NMR analysis at ?80 °C revealed that TiPP predominantly formed a 1:1 complex with NIPAAm, although primary alkyl phosphates preferentially formed a 1:2 complex with NIPAAm. Thus, it was concluded that a slight increase in the bulkiness of the added phosphates influenced the stoichiometry of the NIPAAm–phosphate complex at lower temperatures, and consequently a drastic change in the effect on the stereospecificity of NIPAAm polymerization was observed. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3899–3908, 2005     

All‐atom polarizable force field for DNA based on the classical drude oscillator model

Presented is a first generation atomistic force field (FF) for DNA in which electronic polarization is modeled based on the classical Drude oscillator formalism. The DNA model is based on parameters for small molecules representative of nucleic acids, including alkanes, ethers, dimethylphosphate, and the nucleic acid bases and empirical adjustment of key dihedral parameters associated with the phosphodiester backbone, glycosidic linkages, and sugar moiety of DNA. Our optimization strategy is based on achieving a compromise between satisfying the properties of the underlying model compounds in the gas phase targeting quantum mechanical (QM) data and reproducing a number of experimental properties of DNA duplexes in the condensed phase. The resulting Drude FF yields stable DNA duplexes on the 100‐ns time scale and satisfactorily reproduce (1) the equilibrium between A and B forms of DNA and (2) transitions between the BI and BII substates of B form DNA. Consistency with the gas phase QM data for the model compounds is significantly better for the Drude model as compared to the CHARMM36 additive FF, which is suggested to be due to the improved response of the model to changes in the environment associated with the explicit inclusion of polarizability. Analysis of dipole moments associated with the nucleic acid bases shows the Drude model to have significantly larger values than those present in CHARMM36, with the dipoles of individual bases undergoing significant variations during the MD simulations. Additionally, the dipole moment of water was observed to be perturbed in the grooves of DNA. © 2014 Wiley Periodicals, Inc.     

Fully polarizable QM/MM calculations: An application to the nonbonded iodine–oxygen interaction in dimethyl‐2‐iodobenzoylphosphonate

The compound dimethyl‐2‐iodobenzoylphosphonate is unusual in that it forms well‐ordered crystals that clearly show short iodine‐oxygen interactions in which both the iodine and the oxygen are in their normal oxidation states. These interactions were studied using a new hybrid quantum mechanical–molecular mechanical approach that employs a polarizable molecular mechanics component. The electric field at the molecular mechanics atoms was calculated from a distributed multipole expansion of the wave function; this induced dipoles on the molecular mechanics atoms. The electrostatic potential in a spherical shell around the induced dipoles was reproduced through induced charges on the atomic center and those bonded to it using an analytical (rather than numerical) procedure. The new atomic charges (induced charges plus permanent charges) were then able to interact with the quantum mechanical entity and polarize the wave function. The procedure was iterated to convergence. The calculations show that the iodine atom becomes more positive in the crystal environment (modeled by a chain of three molecules of dimethyl‐2‐iodobenzoylphosphonate). Thus, while the cooperative effects of the crystal environment may not be the only feature stabilizing this unusual interaction, they do play a significant role in reducing the otherwise unfavourable iodine–oxygen monopole–monopole interaction. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 478–482, 2000     

Dual roles of alkyl alcohols as syndiotactic‐specificity inducers and accelerators in the radical polymerization of N‐isopropylacrylamide and some properties of syndiotactic poly(N‐isopropylacrylamide)

The effects of simple alkyl alcohols on the radical polymerization of N‐isopropylacrylamide in toluene at low temperatures were investigated. We succeeded in the induction of syndiotactic specificity and the acceleration of polymerization reactions at the same time by adding simple alkyl alcohols such as 3‐methyl‐3‐pentanol (3Me3PenOH) to N‐isopropylacrylamide polymerizations. The dyad syndiotacticity increased with a decrease in the temperature and an increase in the bulkiness of the added alcohol and reached up to 71% at ?60 °C in the presence of 3Me3PenOH. With the assistance of NMR analysis, it was revealed that the alcohol compounds played dual roles in this polymerization system; an alcohol compound coordinating to the N? H proton induced syndiotactic specificity, and that hydrogen‐bonded to the C?O oxygen accelerated the polymerization reaction. The effect of syndiotacticity on the properties of poly(N‐isopropylacrylamide)s was also examined in some detail. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4450–4460, 2006