Microsolvation of 2-azetidinone: a model for the peptide group–water interactions

Abstract

2-Azetidinone-water clusters can be considered as appropriate models for investigating the interaction of the peptide functional group with water. The rotational spectra of 2-azetidinone-(H2O)n (n = 1, 2) complexes have been studied in the 6-18 GHz frequency range using a molecular beam Fourier transform microwave spectrometer. Two different isomers have been observed for the 1 : 1 adduct. The most stable (1 : 1a) is stabilized by two hydrogen bonds O-H···O=C and N-H···O with water closing a ring with the peptide group. For the other conformer (1 : 1b), water is placed on the other side of the carbonyl group stabilized by O-H···O=C and C-H···O hydrogen bonds. In 2-azetidinone-(H2O)2 the water molecules close a ring with the peptide group forming three different hydrogen bonds: O-H···O=C, O-H···O and N-H···O. The spectra of the parent and several isotopologues of each cluster have been investigated in order to determine their structures. The hydrogen bond geometries show that the dominant interaction is the O-H···O=C hydrogen bond, in good agreement with the observed preference of water to interact with this group in proteins. A comparison between the geometries of the different observed adducts shows clearly how cooperative hydrogen bonding plays an important role in the stabilization of these complexes. No detectable structural changes have been observed for 2-azetidinone upon hydration with one water molecule.

Hydrogen‐Bond Cooperativity in Formamide2–Water: A Model for Water‐Mediated Interactions

“…The r s coordinates are collected in Table S13 of the Supporting Information. The r 0 data and the details of the calculations are collected in Table S14 were they are compared to those of ab initio calculations.T he experimental structure (see Figure 3) reflects that the two formamide subunits close as equential cycle with water through three hydrogen bonds,C = O···H À N, N À H···OH, and O À H···O = C. This is possible thanks to the hydrogen bond donor/acceptor double character of both water and formamide molecules.The hydrogen bond lengths indicate that the dominant interaction is OÀH···O=Ca sr eported for related systems [11,12] and in agreement with the observed preference of water to interact with this group in globular proteins. [1] Thesocalled s-bond cooperativity is associated to chains or cycles of hydrogen bonds between groups acting simultaneously as donor and acceptor.…”

“…Different examples of investigations on isolated hydrated amide clusters performed in supersonic jets by microwave spectroscopy can be found in the literature. [9][10][11][12][13][14][15][16] These works,i np articular the detailed investigation of the structures of formamide-(H 2 O) n (n = 1,2) [11] (see Figure 1), have led to the observation of the conformers build from the different docking sites of formamide and some of the structural signatures of the cooperative hydrogen-bonding effects.H erein we have undertaken the study of one of the simplest systems modelling amide-amide and amide-amide water-mediated interactions,t he complex formed by two molecules of formamide and one water molecule (f 2 w, see Figure 1). We have payed special attention to accurately determine its structure and the nuclear quadrupole coupling hyperfine constants of the two 14 Nn uclei to search for the subtle signatures of cooperative effects,p articularly those which cause the inductive polarization of the amide group.…”

Hydrogen‐Bond Cooperativity in Formamide2–Water: A Model for Water‐Mediated Interactions

“…Different examples of investigations on isolated hydrated amide clusters done in supersonic jets by microwave spectroscopy can be found in the literature. [20,[24][25][26][27][28][29][30] These works, in particular the detailed investigation of the structures of formamide-(H2O)n [25] (see Figure 1) (n=1,2), have led to interesting pieces of information. The observation of the conformers build from the different docking sites of formamide led to conclude that the dominant interaction results to be the HB of water with the amide carbonyl group as found in globular proteins.…”

Water-Induced Structural Changes in Crown Ethers from Broadband Rotational Spectroscopy

“…This approach is applicable when the position of all water molecules have been determined to test changes in the structure of a monomer upon complexation. 27,28 Using this approach, we could identify the 12C4 backbone in the 12C4-w 2 rotamer as the CIV-W 2 form related to conformer CIV ( Figure 5), as confirmed by the calculated rotational constants (see Table 1) and the experimentally determined oxygen atom positions (see Table S7). Using the same approach (see Table S10) it was possible to identify conformers CI and CIV of 12C4 as the backbones of rotamers CI -WI and CIV-WI, respectively.…”