Intramolecular Hydrogen Bond NH Research Articles

Destruxin E backbone modification effects on osteoclast Morphology: Synthesis and SAR study of N-Desmethyl and N-Methyl analogs

The design and synthesis of N-desmethyl and N-methyl destruxin E analogs have been demonstrated. The X-ray single crystal structure of destruxin E (1a) revealed a stable three-dimensional (3D) structure, including a s-cis amide bond at the MeVal–MeAla moiety and two intramolecular hydrogen bonds between NH(β-Ala) and OC(Ile) and between NH(Ile) and OC(β-Ala). N-Desmethyl analogs 2a (MeAla → Ala) and 2b (MeVal → Val) were synthesized through macrolactonization similar to our previously reported synthesis of 1a. Conversely, for the synthesis of N-methyl analogs 2c (Ile → MeIle) and 2d (β-Ala → Meβ-Ala), macrolactonization did not proceed; therefore, cyclization precursors 10c and 10d were designed to maintain the intramolecular hydrogen bonds described above during their cyclization. The macrolactamization proceeded despite the presence of a less reactive N-methylamino group at the N-terminus in both cases. Analog 2a, which exhibits multiple conformers in solutions, was inactive at 50 μM, whereas analog 2b, which exhibits a conformation similar to that of 1a in solutions, exhibited morphological changes against osteoclast-like multinuclear cells at 1.6 μM. The activity of the MeIle analog 2c, which cannot take the intramolecular hydrogen bond (Ile)NH•••OC(β-Ala) in 1a, was markedly diminished compared with that of 1a, and that of the Meβ-Ala analog 2d, which cannot take the intramolecular hydrogen bond (β-Ala)NH•••OC(Ile) in 1a, was further reduced to one-fourth of that of 2c. The overall results indicate that both the s-cis amide bond at the MeVal–MeAla moiety and two intramolecular hydrogen bonds (β-Ala)NH•••OC(Ile) and (Ile)NH•••OC(β-Ala) are important for constraining the conformation of the macrocyclic peptide backbone in destruxin E, thereby exhibiting its potent biological activity.

Investigation of pyramidal inversion of nitrogen atom in carbamate and thiocarbamate ions formed at the reaction of СО2, СOS, CS2 with 2-aminoethanol

Dynamic NMR was applied to measuring the value ΔG≠ characterizing the height of the barrier to the pyramidal inversion of the nitrogen atom in carbamate and thiocarbamate anions formed at the reaction of 2-aminoethanol with CO2 and COS. The refinement was introduced in formerly suggested cyclic structures of anions containing an intramolecular hydrogen bond NH···O(S), which contradicted the found large values of the barrier of inversion (ΔG ≠ ∼ 70 kJ mol–1). The hydrogen bond in the cyclic anions of carbamates and thiocarbamates is two-electron and three-center. Analogous cyclic structure with a multicenter hydrogen bond does not form in the case of dithiocarbamate anion that is the product of 2-aminoethanol reaction with CS2.

Solution and solid-state study of the structure of azo-coupling products from isomeric enaminones possessing tert-butyl group: An unprecedented observation of pure hydrazo form in azo coupled N-alkyl β-enaminones

The structure of the azo-coupling products from enaminones derived from 4,4-dimethyl-1-phenylpentane-1,3-dione has been studied by means of solution-state 1H, 13C and 15N NMR spectroscopy and X-ray diffractometry. The presence of bulky tert-butyl group hinders or even prevents from the formation of planar conjugated heterodiene system HNCCNN with an intramolecular hydrogen bond NH⋯N which is the prerequisite for fast tautomeric exchange imino-hydrazo – enamino-azo. The minor amount of azo compounds is formed by a proton exchange through a hydrogen bond NH⋯N, which is either intramolecular (in solution) or intermolecular (solid state). The intermolecular exchange proceeds via the dimers of the azo coupling products. This is unprecedented result among the similar molecules hitherto studied.

Conformational structure of N-(silylmethyl)anilines PhNHCH2SiMe n (OEt)3-n (n = 0–3)

As show the data of IR spectroscopy and quantum-chemical calculations (B3LYP/6-311+G**), N-(silylmethyl)anilines PhNHCH2SiMen(OEt)3−n in inert media have an intramolecular hydrogen bond NH⋯OSi. N-[(Trimethylsilyl)methyl]aniline PhNHCH2SiMe3 in inert solvents exists as a mixture of two conformers close in energy.

1H and 13C NMR Study of Bifurcated Intramolecular Hydrogen Bonds in 2,6-Bis(2-pyrrolyl)pyridine and 2,6-Bis(1-vinyl-2-pyrrolyl)pyridine

According to the 1H and 13C NMR data, bifurcated intramolecular hydrogen bond NH⋯N⋯HN in 2,6-bis(2-pyrrolyl)pyridine fixes its molecule in a conformation with syn orientation of the pyrrole rings. An analogous bifurcated hydrogen bond CH⋯N⋯HC is formed in 2,6-bis(1-vinyl-2-pyrrolyl)pyridine. 2-(1-Vinyl-2-pyrrolyl)-6-(2-pyrrolyl)pyridine is characterized by unsymmetrical bifurcated hydrogen bond NH⋯ N⋯HC.

Photoinitiated processes in 1-p-tolylsulfonylazo-2,4,6,8-tetrakis(tert-butyl)phenoxazine

New photochromic compound 1-p-tolylsulfonylazo-2,4,6,8-tetrakis(tert-butyl)phenoxazine containing the intramolecular hydrogen bond NH...N and the corresponding model structures 2,4,6,8-tetrakis(tert-butyl)-1-(veratroylazo)phenoxazine and 2,4,6,8-tetrakis(tert-butyl)-N-acetyl-1-(p-tolylsulfonylazo)phenoxazine were synthesized and studied. The data obtained suggested the mechanism of the photoreaction resulting in the accumulation of betaine 1-hydroxy-2,4,6,8-tetrakis(tert-butyl)-10-tolylsulfonylphenoxazin-9-one. The photochromic transformations in the molecule under study are due to intramolecular proton phototransfer followed by E–Z-isomerization about the N–N bond and the formation of betaine 1-hydroxy-2,4,6,8-tetrakis(tert-butyl)-10-tolylsulfonylphenoxazin-9-one. The molecular and crystal structure of the photoproduct was studied by X-ray analysis.

Crystal Structure of the E-2,4-Dinitrophenylhydrazone of 2-Acetyl-3-phenyl-5-methylfuran

The molecular structure of the title E-(syn)-2,4-dinitrophenylhydrazone (DNPH) has been determined and compared with that of the known parent ketone. Semiempirical (AM1, PM3) and molecular mechanics (MM+, Sybyl) calculations gave inconclusive results regarding the possible configurations (syn versus anti) and conformations (s-cis versus s-trans). In the crystal the title molecule is almost planar in an s-trans conformation with the phenyl ring twisted by 30.0° out of the furan plane. Thus, the present DNPH, in the syn configuration, mimics very well the conformation of the parent crystalline ketone. The previous assignment based on solution data of this DNPH as anti is incorrect. It is thus shown that due to the strong intramolecular hydrogen bond NH⋯O2N (ortho) within the DNPH part, the syn-anti DNPH formation is not affected by the putative hydrogen bond to the furanic oxygen atom.

Spectral manifestations of non-additivity of hydrogen bonds in complexes of substituted anthranilic acids

In IR spectra of complexes of N-methyl- and N-phenylanthranilic acids with acceptors of the RCOOH ⋯ B type, the νNH band of the group taking part in the intramolecular hydrogen bond NH ⋯ OC shifts to lower frequencies with an increase of the proton accepting ability of B. The intermolecular hydrogen bond of the C  O ⋯ HX type of methyl esters of these acids with proton donors results in a decrease of the νNH frequency. The strengthening (weakening) of the intramolecular bond is caused by a shift of electron density towards (from) the proton accepting site under the influence of the external proton acceptor (donor). The whole effect of the cooperative and anticooperative influence of the intermolecular hydrogen bond on the intramolecular hydrogen bond reaches 100–130 cm −1.

The weakening of the intramolecular hydrogen bond NH⋯O in complexes of ortho-substituted anilines with proton acceptors

The IR spectra of ortho-nitroaniline and methyl anthranilate and their complexes with protonacceptors B have been studied in the region of the stretching vibrations of the NH 2, ND 2 and NHD groups. Weakening of the intramolecular hydrogen bond NH⋯O under the influence of the intermolecular bond NH⋯B has been found to occur. The cooperativity effect increases with the strength of the inter- and intramolecular hydrogen bonds. A method of estimating the intramolecular hydrogen-bond enthalpy in ortho-substituted anilines has been proposed, based on the assumption of the equality of two hydrogen-bond enthalpies in the complex with the symmetrically perturbed amino group. The equivalence of inter- and intramolecular perturbations were determined by the coincidence of cis- and trans-NH (and/or ND) frequencies of the NHD group.

Condensed heterocycles 47. Intramolecular hydrogen bonding in heteroaromatic hydroxy-, mercapto-, and selenolaldimines

Examination of the PMR spectra of benzo[b]furan and benzo[b]thiophene hydroxy-,mercapto-, and selenolaldimines, obtained in different solvents, show the absence of any correlation between the chemical shifts of the NH protons in aldimines and the strength of the intramolecular hydrogen bond (IMHB) NH...X (X = O, S, or Se). Novel condensed thio- and selenopyrans have been obtained from these aldimines and acrylonitrile. The conditions for the reaction are shown to depend on the strength of the IMHB in the aldimines.

Spectral characteristics, molecular structure, and hydrogen bonding in arylhydrazones of benzoyl chlorides and aromatic aldehydes

1. A study has been made of the IR and PMR spectra of arylhydrazones of benzoyl chlorides and arylhydrazones of benzaldehydes. The changes inν NH of the arylhydrazones of benzoyl chlorides when the change is made from solutions to crystals can be explained by realization of a weak intramolecular hydrogen bond (INTRAHB) NH...Cl in the crystals. 2. In the 2-nitrophenylhydrazones of benzoyl chloride and benzaldehyde, there is an NH...O(O2N) INTRAHB. In proton-acceptor solvents (dioxane, Me CN, DMSO, hexametapol), the arylhydrazones of benzoylchlorides and the arylhydrazones of aromatic aldehydes in which the NH does not participate in an INTRAHB form an intermolecular H-bond with the solvent. The character of the intermolecular interactions of the arylhydrazone of benzoyl chloride) or specific (phenylhydrazone of benzaldehyde). 3. X-ray structure analysis of the phenylhydrazone of benzaldehyde does not reveal any intermolecular contacts shorter than the sum of the van der Waals radii.

Etude spectroscopique de derives mercuriques d'amides-thiols: I. Spectres de vibration et structure des thiol-2 N-méthylacétamide, thiol-3 N-méthylpropanamide et N-(thiol-2 éthyle) acétamide

Raman and infrared spectra of CH 3NHCOCH 2SH, CH 3NHCO(CH 2) 2SH and CH 3CONH(CH 2) 2SH have been recorded between 3800 and 200 cm −1. Some structural information is obtained from their analysis: for pure liquids or solids, molecules form linear chains with NH ⋯ OC hydrogen bonds, the SH group being probably bound to the oxygen of an adjacent molecule. For CCl 4 solutions, an intramolecular hydrogen bond NH ⋯ S is observed for the first compound only, corresponding to the formation of a five-membered ring.

Some transformations of enamino carbonyl compounds

1. Based on the data of the NMR spectra, the en-N-monoalkylamino-β-keto esters represent exclusively the cis-isomers as the chelates, which are stabilized by an intramolecular hydrogen bond NH... O =C(CH3); exchange between the cis- and trans-isomers is absent in the enamino ketones under equilibrium conditions when the temperature is varied; in enamino ketones, including those containing a tertiary amino group, the Hα proton is easily replaced by deuterium. 2. Enamino ketones react with cyanoacetic ester under mild conditions to give the esters of 5-amino-2-carbamoyl-2,4-hexadienoic acid, while enamino-β-keto esters and α-alkyl ketones react to give 2-pyridone derivatives.