The C—H⋯O hydrogen bond. An ab initio study of nitrosomethane and its hydrogen bonded dimer

In order to study the short C—H?O contact which has been found in several nitroso compounds, a series of ab initio calculations have been performed on nitrosomethane and it's cyclic “hydrogen bonded” dimer. A potential function for the C—H?O contact has been found and the effect of this contact upon the NO and CN bonds has been studied. The potential is shallow with a minimum of only ?2.65 kcal mol^?1 for each contact and the equilibrium C?O distance is 3.524, A. These results indicate that the C—H?O bond is better described as a van der Waal's type contact than a hydrogen bond. The equilibrium length of the NO bond (R_NO) changes in a regular manner with variations in the C?O (R_HYD) distance, i.e. when R_HYD becomes shorter R_NO becomes longer. However, the variations in the CN bond lengths, which in the nitrosomethane monomer molecule is a long and weak bond, are anomalous.     

A comparative ab initio study of some molecular systems based on hydrazine and formamide

A series of ab initio calculations has been performed on formamide and its hydrogen bonded dimer, s-diformylhydrazine, s-dimethylhydrazine and hydrazine. All systems were assumed planar. The CO, CN and NN bond lengths were optimized in all cases, in order to study the changes of these bonds with variations in the environment. Gross atomic populations and force constants were also considered, and in some calculations the effect of basis enlargements was studied. Significant changes were found in the formamide unit upon dimerization via hydrogen bonds or a NN bond. And, also, a systematic variation was found for the NN bond by going from hydrazine via dimethylhydrazine to diformylhydrazine. The results of this study indicate that the effect of substitution within the framework used is well simulated by ab initio calculations.     

The effect of hydrogen bonding on structural parameters I: An ab initio study of the keto and enol tautomers of formamide and their hydrogen bonded dimers

In order to study the variation of CO and CN bond lengths as functions of the hydrogen bond length, a series of ab initio calculations have been performed on the keto and enol tautomers of formamide. The formation of hydrogen bonds leads to an increase in the conjugation of the NCO fragment. This increase is expressed as a lengthening of the double bonds and a corresponding shortening of the single bonds. These changes are found to vary with the length of the hydrogen bonds and analytical expressions for these variations of the bond lengths have been derived. The potential functions for dimerization, i.e. formation of, respectively, two N-H ·· O and two O-H ·· N hydrogen bonds have also been found. The results obtained indicate significant differences between the two types of hydrogen bonds.     

The effect of hydrogen bonding on structural parameters ii. an ab initio study of the monohydrated formamide molecule

Four hydrogen-bonded formamide-water complexes have been studied by ab initio calculations, two where the amino group acts as a donor and two where the carbonyl oxygen is an acceptor. The results indicate that the effect on the conjugated NCO fragment depends on both the type and the energy of the hydrogen bond formed. Although, in all cases the formation of a hydrogen bond leads to increased conjugation, expressed as a shortening of the CN bond and a corresponding lengthening of the CO bond, there is a significant difference in the effect of the two types of hydrogen bonds. This difference may be explained by changes in the electron populations. In two of the complexes the effect of varying the hydrogen bond length has been studied in some detail. It is found that the effect on the conjugated system depends on the length of the hydrogen bond, and analytical expressions have been found for the variations of the CO and CN bond lengths with changes in the hydrogen bond length. Potential functions for the N-H β O and O-H β O hydrogen bonds have also been derived.     

The crystal and molecular structure of delta-9-tetrahydrocannabinolic acid b.

The crystal and molecular structure of the title compound C-22H-30O-4, has been determined by X-ray methods using 1106 reflections above background level collected by counter methods. The crystals are orthorhombic, space group P2-12-12-1 with cell dimensions a equals 16.514(2) A; b equals 14.324(2) A; c equals 8.744(1) A; there are four molecules per unit cell. The structure was refined to an R of 0.084 (weighted R-w equals 0.068). The cyclohexene and the pyran part of the molecule occurs in the half-chair conformation. The bond distances and angles, and a slight twist of the benzene ring, indicate considerable stains in the aromatic system. Both the phenolic and carboxylic group are significantly out of the plane through the aromatig ring. The angle between this plane and a plane through the cyclohexene ring is 37.7 degrees. The pentyl sidechain occurs in an extended gauche conformation, and the thermal parameters of this part of the molecule are very high. The molecules are held together by van der Waals forces in the c-directions, and hydrogen bonds (2.688 A) from phenolic to carboxylic groups in the a-b plane. There is a short ultra-molecular hydrogen bond (2.490 A) from the carboxylic group to the pyran oxygen.     

Stapling of a 3(10)-helix with click chemistry

Short peptides are important as lead compounds and molecular probes in drug discovery and chemical biology, but their well-known drawbacks, such as high conformational flexibility, protease lability, poor bioavailability and short half-lives in vivo, have prevented their potential from being fully realized. Side chain-to-side chain cyclization, e.g., by ring-closing olefin metathesis, known as stapling, is one approach to increase the biological activity of short peptides that has shown promise when applied to 3(10)- and α-helical peptides. However, atomic resolution structural information on the effect of side chain-to-side chain cyclization in 3(10)-helical peptides is scarce, and reported data suggest that there is significant potential for improvement of existing methodologies. Here, we report a novel stapling methodology for 3(10)-helical peptides using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction in a model aminoisobutyric acid (Aib) rich peptide and examine the structural effect of side chain-to-side chain cyclization by NMR, X-ray diffraction, linear IR and femtosecond 2D IR spectroscopy. Our data show that the resulting cyclic peptide represents a more ideal 3(10)-helix than its acyclic precursor and other stapled 3(10)-helical peptides reported to date. Side chain-to-side chain stapling by CuAAC should prove useful when applied to 3(10)-helical peptides and protein segments of interest in biomedicine.