The tendency to adopt β-turn conformation by model dipeptides with α,β-dehydrophenylalanine (ΔPhe) residue in the gas phase and in solution is investigated by theoretical methods. We pay special attention to a dependence of conformational properties on the side-chain configuration of dehydro residue and the influence of N-methylation on β-turn stability. An extensive computational study of the conformational preferences of Z and E isomers of dipeptides Ac-Gly-(E/Z)-ΔPhe-NHMe (1a / 1b) and Ac-Gly-(E/Z)-ΔPhe-NMe(2) (2a/2b) by B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) methods is reported. It is shown that, in agreement with experimental data, Ac-Gly-(Z)-ΔPhe-NHMe has a great tendency to adopt β-turn conformation. In the gas phase the type II β-turn is preferred, whereas in the polar environment, the type I. On the other hand, dehydro residue in Ac-Gly-(E)-ΔPhe-NHMe has a preference to adopt extended conformations in all environments. N-methylation of C-terminal amide group, which prevents the formation of 1←4 intramolecular hydrogen bond, change dramatically the conformational properties of studied dehydropeptides. Especially, the tendency to adopt β-turn conformations is much weaker for the N-methylated Z isomer (Ac-Gly-(Z)-ΔPhe-NMe(2) ), both in vacuo and in the polar environment. On the contrary, N-methylated E isomer (Ac-Gly-(E)-ΔPhe-NMe(2) ) can easier adopt β-turn conformation, but the backbone torsion angles (ϕ(1) , ψ(1) , ϕ(2) , ψ(2) ) are off the limits for common β-turn types.

The applicability of popular and efficient B3LYP hybrid density functional and medium-size Popletype basis set in combination with computationally expensive anharmonic model to obtain more accurate theoretical structure, vibrational frequencies and GIAO NMR parameters of cytosine was tested. We report on prediction of cytosine equilibrium (R e) and rovibrationally averaged (R v) structures and vibrational frequencies in the gas phase and DMSO solution using density functional theory combined with 6-311??G** basis set. The harmonic and anharmonic vibrational frequencies (using second-order vibrational perturbation theory, VPT2) were critically discussed. In comparison with initial harmonic data, a significantly better agreement between scaled and anharmonic frequencies and experiment was observed. Proton and carbon nuclear magnetic shieldings were calculated at R e and R v structures of cytosine in the gas phase and DMSO solution using BHandH and B3LYP density functionals combined with 6-311??G**, aug-cc-pVTZ-J and STO-3G mag basis sets. The obtained NMR results were compared with available experimental data and discussed at length.

The interaction of phenylalanine diamide (Ac-Phe-NHMe) with egg yolk lecithin (EYL) in chloroform was studied by (1)H and (13)C NMR. Six complexes EYL-Ac-Phe-NHMe, stabilized by N-H···O or/and C-H···O hydrogen bonds, were optimized at M06-2X/6-31G(d,p) level. The assignment of EYL and Ac-Phe-NHMe NMR signals was supported using GIAO (gauge including atomic orbital) NMR calculations at VSXC and B3LYP level of theory combined with STO-3Gmag basis set. Results of our study indicate that the interaction of peptides with lecithin occurs mainly in the polar 'head' of the lecithin. Additionally, the most probable lecithin site of H-bond interaction with Ac-Phe-NHMe is the negatively charged oxygen in phosphate group that acts as proton acceptor.

The influence of aqueous environment on the main-chain conformation (ω0 , ϕ, and ψ dihedral angles) of two model peptoids: N-acetyl-N-methylglycine N'-methylamide (Ac-N(Me)-Gly-NHMe) (1) and N-acetyl-N-methylglycine N',N'-dimethylamide (Ac-N(Me)-Gly-NMe₂) (2) was investigated by MP2/6-311++G(d,p) method. The Ramachandran maps of both studied molecules with cis and trans configuration of the N-terminal amide bond in the gas phase and in water environment were obtained and all energy minima localized. The polarizable continuum model was applied to estimate the solvation effect on conformation. Energy minima of the Ac-N(Me)-Gly-NHMe and Ac-N(Me)-Gly-NMe₂ have been analyzed in terms of the possible hydrogen bonds and C = O dipole attraction. To validate the theoretical results obtained, conformations of the similar structures gathered in the Cambridge Crystallographic Data Centre were analyzed. Obtained results indicate that aqueous environment in model peptoids 1 and 2 favors the conformation F (ϕ and ψ = -70º, 180º), and additionally significantly increases the percentage of structures with cis configuration of N-terminal amide bond in studied compounds.

Electron spin resonance (ESR), (1) H-NMR, voltage and resistance experiments were performed to explore structural and dynamic changes of Egg Yolk Lecithin (EYL) bilayer upon addition of model peptides. Two of them are phenylalanine (Phe) derivatives, Ac-Phe-NHMe (1) and Ac-Phe-NMe2 (2), and the third one, Ac-(Z)-ΔPhe-NMe2 (3), is a derivative of (Z)-α,β-dehydrophenylalanine. The ESR results revealed that all compounds reduced the fluidity of liposome's membrane, and the highest activity was observed for compound 2 with N-methylated C-terminal amide bond (Ac-Phe-NMe2 ). This compound, being the most hydrophobic, penetrates easily through biological membranes. This was also observed in voltage and resistance studies. (1) H-NMR studies provided a sound evidence on H-bond interactions between the studied diamides and lecithin polar head. The most significant changes in H-atom chemical shifts and spin-lattice relaxation times T1 were observed for compound 1. Our experimental studies were supported by theoretical calculations. Complexes EYLAc-Phe-NMe2 and EYLAc-(Z)-ΔPhe-NMe2 , stabilized by NH⋅⋅⋅O or/and CH⋅⋅⋅O H-bonds were created and optimized at M06-2X/6-31G(d) level of theory in vacuo and in H2 O environment. According to our molecular-modeling studies, the most probable lecithin site of H-bond interaction with studied diamides is the negatively charged O-atom in phosphate group which acts as H-atom acceptor. Moreover, the highest binding energy to hydrocarbon chains were observed in the case of Ac-Phe-NMe2 (2).