Ab initio studies of hydrogen bonding of N-methylacetamide: structure, cooperativity, and internal rotational barriers

Abstract

Hydrogen bonding interactions and their effect on the structure and the energetics of the rotation about N-Cu and Cu-C' bonds are studied for N-methylacetamide (NMA) by use of ab initio quantum mechanical calculations. The structure and methyl rotational barriers for isolated NMA have k e n determined at the Hartree-Fock (HF) level with 6-31G. 6-31G*, and 6-31 1G** basis sets and at the second-order Mdler-Plesset perturbation (MP2) level with a 6-31G* basis set including geometry optimization for the different methyl orientations. The optimized geometries, the hydrogen bonding interaction energies, and the methyl rotational barriers for 11 complexes in which NMA is hydrogen bonded to H20 and/or formamide (FM) [i.e., NMA + H20 (3 complexes), NMA + 2H20 (2 complexes), NMA + 3H20 (1 complex), NMA + FM (2 complexes), NMA + (FM and H20) (1 complex), NMA + 2FM (1 complex), and NMA + (2FM and 1H2O) (1 complex)] have been calculated at the HF/6-31G level; HF/6-31G* calculations were performed for the 3 NMA + H20 complexes and 1 of the NMA + 2H20 complexes. For isolated NMA, the torsional potentials for both methyl group are predicted to be very flat and the rotational bamers are only -0.1 kcal/mol. This contrasts with some of the earlier calculations in which larger barriers were obtained due to lack of geometry optimization of the rotated conformers. The bamers in the hydrogen bonded systems are calculated to be significantly larger (0.2-0.9 kcaljmol). The increase of the C'=O bond length from the gas-phase to crystallinestate NMA componds to that found in the ab initio calculations with hydrogen bonding ligand^, but the d8erence (0.1 A) in the experimental C'(0)-N bond distance is significantly larger than the calculated value. This suggests that the crystal structure may be in error. In agreement with the crystal structure, the lowest energy conformation in all the hydrogen bonded systems is predicted to have an ecliped (C')CH3 group and a staggered (N)CHp group with respect to the C'(0)-N bond; this contrasts with isolated NMA, where the conformations with the different methyl orientations have similar energies with a difference of only -0.1 kcaljmol. In accord with the general trend observed in hydrogen bonding in a crystal data base, the ab initio calculations show that the hydrogen bond distance involving 'multiple acceptors" (i.e., the C ' 4 group that accepts two hydrogen bonds) is 0.02-0.06 A longer than that involving a 'single acceptor". The calculated hydrogen bond energy is -0.5-1.5 kcal/mol smaller when two acceptors are present. By contrast, the formation of a hydrogen bond to the NH group reduces the hydrogen bond distance for the hydrogen bond to the C ' 4 group by -0.02-0.045 A and increases the corresponding hydrogen bond energy by -0.3-0.9 kcal/mol. Correspondingly, the formation of each hydrogen bond to C ' 4 reduces the hydrogen bond distance for the hydrogen bond to the NH and increases the corresponding hydrogen bond energy by about the same amount. When one ligand is bound to the carbonyl group,...

Interplay of the Intramolecular Water Vibrations and Hydrogen Bond in N-Methylacetamide-Water Complexes: Ab Initio Calculation Studies

“…Although there already exist a number of literatures on ab initio studies of NMA-water complexes, [54][55][56][57][58][59] most of the previous works concerned about H-bond energies, optimized structures, and amide I mode frequency. Guo and Karplus showed that a single NMA molecule has three H-bonding sites (denoted as A, B, and C) as shown in Figure 1.…”

“…Guo and Karplus showed that a single NMA molecule has three H-bonding sites (denoted as A, B, and C) as shown in Figure 1. 54 Using the Gaussian 98 program, 60 we obtained the optimized geometry of NMA-H2O(A) complex at the RHF/6-311++G** level, where the H-bond distance rA (see Fig. 1) is found to be 1.9785 Å.…”

Close agreement between the orientation dependence of hydrogen bonds observed in protein structures and quantum mechanical calculations

“…It is a nontrivial problem to choose a small hydrogen bonded dimer that accurately represents hydrogen bonds found in protein side chains and main chains. Formamide, acetamide, N-methylacetamide (NMA), formamide-formaldehyde, and water dimers (and combinations thereof) have been explored in the literature, primarily with the purpose of identifying various local and global minima in a given complex (9,10,(17)(18)(19)(20)(21)(22)(23). Although NMA dimers are routinely used to model main-chain hydrogen bonds, the methyl groups on both ends can contribute significantly to the dimerization energy surface (13,21), and hence formamide is a better model for amino acid side-chain hydrogen bonds.…”

Optimization of Model Parameters for Describing the Amide I Spectrum of a Large Set of Proteins

“…These effects are here assumed to yield independent and additive shifts of the amide I frequency from the gas phase value ω NMA = 1723 cm −1 of unperturbed, uncoupled NMA, [47][48][49] which has been extensively studied as a model compound of a peptide unit. 31,[50][51][52][53][54][55][56][57] The intrinsic frequency of the amide I oscillator in residue i can thus be described as…”