Interaction between vitamin D receptor and vitamin D ligands: two-dimensional alanine scanning mutational analysis

We present a new method to investigate the details of interaction between vitamin D nuclear receptor (VDR) and various ligands, namely a two-dimensional alanine scanning mutational analysis. In this method, the transactivation of various ligands is studied in conjunction with a series of alanine scanning mutations of the residues lining the ligand binding pocket (LBP) of VDR, and the complete set of results is profiled in a patch table. We investigated examples from four structurally diverse groups of known VDR ligands: the native vitamin D hormone and two compounds with the same side chain configuration; four 20-epi compounds; three 19-nor compounds; and two nonsecosteroids. The patch table of the results indicates characteristics of each group in terms of its interaction with 18 LBP residues. We demonstrate the validity of this approach by application to docking studies of the two nonsecosteroids.     

乙烯-乙烯醇共聚物氢键相互作用与链结构关系的变温溶液氢谱研究

用变温溶液核磁共振氢谱研究了不同组成的乙烯-乙烯醇共聚物在二甲亚砜溶液中的氢键相互作用.结果表明,乙烯醇单元中羟基的信号随温度升高而线性地向高场位移,且不同的三单元组中羟基信号的位移速率不同,表明羟基形成的氢键强度与链结构间存在相关性.     

Noncovalent Lone Pair⋅⋅⋅(No‐π!)‐Heteroarene Interactions: The Janus‐Faced Hydroxy Group

A comparative study using NMR spectroscopy and designed top‐pan molecular balances demonstrates that the noncovalent interaction of a hydroxy group with π‐deficient pyrazine and quinoxaline units involves a lone pair–heteroarene interaction which is much stronger and solvent independent when measured relative to the classical π‐facial hydrogen bond to a benzene ring. Alkyl fluorides also prefer the heteroarene rings over the benzene ring. The attractive interaction between a quinoxaline and a terminal alkyne is also stronger than the intramolecular hydrogen bond to an arene.     

Experimental measurement of carbohydrate-aromatic stacking in water by using a dangling-ended DNA model system

Protein-carbohydrate recognition is of fundamental importance for a large number of biological processes; carbohydrate-aromatic stacking is a widespread, but poorly understood, structural motif in this recognition. We describe, for the first time, the measurement of carbohydrate-aromatic interactions from their contribution to the stability of a dangling-ended DNA model system. We observe clear differences in the energetics of the interactions of several monosaccharides with a benzene moiety depending on the number of hydroxy groups, the stereochemistry, and the presence of a methyl group in the pyranose ring. A fucose-benzene pair is the most stabilizing of the studied series (-0.4 Kcal mol(-1)) and this interaction can be placed in the same range as other more studied interactions with aromatic residues of proteins, such as Phe-Phe, Phe-Met, or Phe-His. The noncovalent forces involved seem to be dispersion forces and nonconventional hydrogen bonds, whereas hydrophobic effects do not seem to drive the interaction.     

Studies of adsorption of 2,2′-bipyridyl on the surface of highly regulated silica matrix of the MCM-41 type by means of <Superscript>15</Superscript>N NMR spectroscopy

The study of 2,2′-bipyridyl adsorption on the surface of highly regular MCM-41 silica at 300 and 130 K was carried out by the ¹⁵N NMR spectroscopy. It was shown that at 300 K the adsorbed molecules were involved in the processes of isotropic reorientation accompanied by the formation and rupture of hydrogen bonds with the surface-located hydroxy groups. Each molecule of 2,2′-bipyridyl forms no more than one hydrogen bond at a time, and their surface density is about one molecule per 1 nm² of the surface. At 130 K 2,2′-bipyridyl forms a monolayer on the surface of silica including about 1.6 molecule per 1 nm². In this monolayer each molecule forms a hydrogen bond with one hydroxy group and prevents the interaction of the other bipyridyl molecules with one more hydroxy group.     

Separation behaviors of xylenol isomers by gas chromatography with helps of hydrogen bonding

Summary Xylenol isomers can be resolved on most polyols (sugars or sugar alcohols) and polyethers (polyethylene glycol or polypropylene glycol) with hydrogen-bonding interaction. They are separated on vinical polyols which have more hydroxy hydrogen than tetrol, and even on vicinal triol when its hydroxy hydrogen is acidic (stronger proton donor). The stronger is the hydrogen bonding interaction between xylenols and the liquid phase, the better is the separation of 2,4- and 2,5-xylenol, and the poorer the separation of 2,4-and 2,3-xylenol.     

Synthesis of vitamin D(3) and calcitriol dimers as potential chemical inducers of vitamin D receptor dimerization

The design and synthesis of vitamin D(3) dimers 2 and 3 and 1 alpha, 25-dihydroxyvitamin D(3) (calcitriol) dimers 4 and 5 are described. The dimers were designed with a view to doubly binding the vitamin D receptor (VDR) and inducing the receptor homodimerization. In the dimers the units are linked through the C-11 position in ring C by an alkyl side chain of six or 10 carbon atoms, far from the hydroxy groups responsible for the VDR binding. The linker is formed by olefin metathesis of an olefinic side chain at the C-11 position introduced by stereoselective cuprate addition. The synthesis, which is both short and convergent, uses the Wittig-Horner approach to construct the vitamin D triene system and allows the preparation of dimers with a linker of modulated length with the purpose of optimizing the vitamin D(3)-VDR interaction.     

Theoretical study of intramolecular hydrogen bonding and molecular geometry of 2-trifluoromethylphenol

The conformational behavior of 2-trifluoromethylphenol was investigated by means of theoretical calculations. Four characteristic structures have been found on the potential energy hypersurface of the compound: anti form (local minimum), in which the hydroxy hydrogen points away from the trifluoromethyl group; and three syn forms (the hydrogen points towards the trifluoromethyl group), with different trifluoromethyl torsions (global minimum, one low and another one high lying saddle-point). The geometry of these conformers were optimized by ab initio calculations using 6-31G** basis set. The effects of electron correlation were investigated by MP2 and various DFT methods. To investigate the intramolecular interaction in the syn forms, the electron density distribution was calculated at the MP2 level of theory. In the structure corresponding to the global minimum at the MP2/6-31G** level a bond critical point was found in Bader's sense between the hydroxy hydrogen and a fluorine of the trifluoromethyl group indicating hydrogen bonding interaction. The length of the hydrogen bond, 1.98 Å, corresponds to medium strength interaction. The O(SINGLE BOND)H bond is slightly twisted and the C(SINGLE BOND)F bond, interacting with it, is considerably twisted out of the plane of the benzene ring to the same side of the ring. The most pronounced geometrical consequence of the hydrogen bond is the 0.02-Å lengthening of the C(SINGLE BOND)F bond participating in its formation. All the other geometrical changes in 2-trifluoromethylphenol, as compared with trifluoromethylbenzene and phenol, are also consistent with the phenomenon of resonance-assisted hydrogen bonding. © 1996 by John Wiley & Sons, Inc.     

Synthesis and structures of 10-hydroxy- and 10-acetoxy-6(5H)phenanthridinones

Treatment of 2,4,8,10-tetranitro-6(5H)-phenanthridinone with hexamethylphosphoric triamide leads to intermolecular nucleophilic substitution of the nitro group by a hydroxy group, the source of which is the water contained in the solvent, to give 10-hydroxy-2,4,8-trinitro-6(5H)-phenanthridinone. An intramolecular interaction with the participation of a proton of the aromatic ring and an oxygen atom of the hydroxy or acetoxy group of the 10-hydroxy- or 10-acetoxy-2,4,8,-trinitro-6(5H)-phenanthridinone, the properties of which are characteristic for an intramolecular hydrogen bond, was detected by x-ray diffraction analysis and PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–319, March, 1987.     

The effect of a lateral hydroxy substituent on the thermal stability of the chiral smectic C phase

This article describes how the inclusion and positioning of a lateral hydroxy group influences the thermal stability of a chiral smectic C phase. An off-central position of the hydroxy group in the aromatic core has the effect of enhancing the thermal stability of the chiral smectic C phase, whereas a central position of the hydroxy group destabilizes it to the extent that there is no evidence for the phase being present. The results indicate that a hydroxy group ortho- to an ester function gives intra- rather than inter-molecular hydrogen bonding. The effects seen with lateral and terminal hydroxy groups are compared with those for analogous fluoro-substituted systems.     

Hydrogen‐bonding patterns of two dihydroxy­lactone derivatives

In the hydrogen‐bonding networks of 8‐hydroxy‐5‐hydroxy­methyl‐3,6‐dioxatricyclo­[6.3.1.0^1.5]dodecan‐2‐one and 5,7‐bis(hydroxy­methyl)‐3,6‐dioxatricyclo­[5.3.1.0^1.5]undecan‐2‐one, both C₁₁H₁₆O₅, layers and double strands, respectively, lead to the formation of chains connected by hydroxy‐to‐hydroxy contacts, where the hydroxy­methyl group, present in both structures, acts as a donor. The secondary structures differ in the hydrogen bonding of these chains via the second hydroxy group, which is involved in hydroxy‐to‐carbonyl and hydroxy‐to‐hydroxy bonds, respectively.     

Three in One: The Versatility of Hydrogen Bonding Interaction in Halide Salts with Hydroxy-Functionalized Pyridinium Cations

The paradigm of supramolecular chemistry relies on the delicate balance of noncovalent forces. Here we present a systematic approach for controlling the structural versatility of halide salts by the nature of hydrogen bonding interactions. We synthesized halide salts with hydroxy-functionalized pyridinium cations [HOC_nPy]⁺ (n=2, 3, 4) and chloride, bromide and iodide anions, which are typically used as precursor material for synthesizing ionic liquids by anion metathesis reaction. The X-ray structures of these omnium halides show two types of hydrogen bonding: ‘intra-ionic’ H-bonds, wherein the anion interacts with the hydroxy group and the positively charged ring at the same cation, and ‘inter-ionic’ H-bonds, wherein the anion also interacts with the hydroxy group and the ring system but of different cations. We show that hydrogen bonding is controllable by the length of the hydroxyalkyl chain and the interaction strength of the anion. Some molten halide salts exhibit a third type of hydrogen bonding. IR spectra reveal elusive H-bonds between the OH groups of cations, showing interaction between ions of like charge. They are formed despite the repulsive interaction between the like-charged ions and compete with the favored cation-anion H-bonds. All types of H-bonding are analyzed by quantum chemical methods and the natural bond orbital approach, emphasizing the importance of charge transfer in these interactions. For simple omnium salts, we evidenced three distinct types of hydrogen bonds: Three in one!     

Electrochemical modeling of antioxidants action and determination of their activity

The method of pulse voltammetry was applied to the investigation of the antioxidant activity of sulfur-containing biologically active substances. Three models were considered to characterize the substances in aqueous medium: First, the interaction of antioxidants with a ferrous ion to characterize the preventive activity on the initiation stage of free radical oxidation, second and third describing the interaction of an antioxidant with electrochemically generated hydroxy radicals and hydrogen peroxide, to characterize the inhibitory activity in the initial stages of propagation and branching of the chain of free radical oxidation. A synergistic effect of ascorbic acid and other studied compounds at their combined action on hydroxy radicals and hydrogen peroxide was revealed.     

A conformational analysis of the methyl ester of O-acetyl-L-lactyl-L-alanine and the methylamide of N-acetyl-L-alanyl-L-lactic acid

Summary 1. The most preferred extended conformations for Ac-L-Lac-L-Ala-OMe and Ac-L-Ala-L-Lac-NHMe in a polar medium are R-R, R-B, B-R, and B-B. Of the conformations with a hydrogen bond of the 1–4 type, the most stable are R-R and R-B.2. There is an interrelationship between the conformational states of neighboring hydroxy and amino acid residues.3. The stereochemical characteristics of the ester group are similar to those of the amide group.M. M. Shemyakin Institute of the Chemistry of Natural Compounds, Academy of Sciences of the USSR. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 191–194, March, 1971.     

Selective cleavage of methoxy protecting groups in carbohydrates

The selective cleavage of methoxy protecting groups next to hydroxy groups is achieved using a radical hydrogen abstraction reaction as the key step. Under the reaction conditions, the hydroxy group generates an alkoxyl radical that reacts with the sterically accessible adjacent methoxy group, which is transformed into an acetal. In the second step, the acetals are hydrolyzed to give alcohols or diols. A one-pot hydrogen abstraction-hydrolysis procedure was also developed. Good yields were usually achieved, and the mild conditions of this methodology were compatible with different functional groups and sensitive substrates such as carbohydrates.     

Spectroscopic Observation of the Hydroxy Position in Butanol Hydrates and Its Effect on Hydrate Stability

In this study, we investigate the crystal structures and phase equilibria of butanols+CH₄+H₂O systems to reveal the hydroxy group positioning and its effects on hydrate stability. Four clathrate hydrates formed by structural butanol isomers are identified with powder X‐ray diffraction (PXRD). In addition, Raman spectroscopy is used to analyze the guest distributions and inclusion behaviors of large alcohol molecules in these hydrate systems. The existence of a free OH indicates that guest molecules can be captured in the large cages of structure II hydrates without any hydrogen‐bonding interactions between the hydroxy group of the guests and the water‐host framework. However, Raman spectra of the binary (1‐butanol+CH₄) hydrate do not show the free OH signal, indicating that there could be possible hydrogen‐bonding interactions between the guests and hosts. We also measure the four‐phase equilibrium conditions of the butanols+CH₄+H₂O systems.     

端基对超支化高分子性质影响的研究

对端羟基脂肪族超支化高分子的端基进行了乙酰化和硅烷化改性，研究了不同端基对超支化高分子的玻璃化温度，折光指数增量以及特性粘度的影响。结果表明，端基的极性减小使超支化高分子的玻璃化温度降低，不同端基的超支化高分子的折光指数增量也有很大差异，而强极性的端基使超支化高分子在溶液中易产生团聚作用。由于端基在超支化高分子中所占比重较大，端基是影响超支化高分子性质的重要因素。     

Hydrogen-bonding cooperativity: using an intramolecular hydrogen bond to design a carbohydrate derivative with a cooperative hydrogen-bond donor centre

Neighbouring groups can be strategically located to polarise HO.OH intramolecular hydrogen bonds in an intended direction. A group with a unique hydrogen-bond donor or acceptor character, located at hydrogen-bonding distance to a particular OH group, has been used to initiate the hydrogen-bond network and to polarise a HO.OH hydrogen bond in a predicted direction. This enhanced the donor character of a particular OH group and made it a cooperative hydrogen-bond centre. We have proved that a five-membered-ring intramolecular hydrogen bond established between an amide NH group and a hydroxy group (1,2-e,a), which is additionally located in a 1,3-cis-diaxial relationship to a second hydroxy group, can be used to select a unique direction on the six-membered-ring intramolecular hydrogen bond between the two axial OH groups, so that one of them behaves as an efficient cooperative donor. Talose derivative 3 was designed and synthesised to prove this hydrogen-bonding network by NMR spectroscopy, and the mannopyranoside derivatives 1 and 2 were used as models to demonstrate the presence in solution of the 1,2-(e,a)/five-membered-ring intramolecular hydrogen bond. Once a well-defined hydrogen-bond is formed between the OH and the amido groups of a pyranose ring, these hydrogen-bonding groups no longer act as independent hydrogen-bonding centres, but as hydrogen-bonding arrays. This introduces a new perspective on the properties of carbohydrate OH groups and it is important for the de novo design of molecular recognition processes, at least in nonpolar media. Carbohydrates 1-3 have shown to be efficient phosphate binders in nonpolar solvents owing to the presence of cooperative hydroxy centres in the molecule.     

The C4-functionalized 9,10-seco-5,7,10(19)-cholestatriene derivatives: Concise synthesis and characterization of novel vitamin D analogues with a four-membered heterocyclic ether

Two novel stereoisomeric 9,10-seco-steroids (3a,b) bearing a spiro-oxetane at the C2 position of the A-ring with an unconventional C4-hydroxy group have been designed and synthesized by a convergent manner. The requisite A-ring enyne precursors (±)-9 were prepared in excellent yield from our reported aldehyde 4 according to a five-step procedure. The absolute configurations at the C4-hydroxy groups of the targeted compounds (3a,b) were determined by the circular dichroism (CD) exciton chirality method using the corresponding benzoates of the C4-allylic alcohol. Preliminary biological characterization using the bovine thymus VDR suggested that the incorporation of a spiro-oxetane at the C2 position, in combination with a hydroxy group at the C4 position, had negative effects on the VDR affinity.     

Kinetik der Bromierung von Phenolen und phenolischen Mehrkernverbindungen, 5. Mitt.

The kinetics of the bromination of six differently substituted 2,6-bis(hydroxybenzyl)phenols having only one reactivepara position at the phenolic unit in the middle of the molecule were studied in acetic acid at 22°C. The reaction rate decreases if intramolecular hydrogen bonds between one or two hydroxy groups of the adjacent phenolic units and the hydroxy group of the reacting unit become possible, and it is especially low, if these hydrogen bonds are directed to the middle by bulky substituents inortho position. This must be explained by a smaller +M-effect of the hydroxy group of the reacting unit. A kinetic isotope effect is observed in deutero acetic acid, where the reaction rate is decreased by the same amount for compounds with and without intramolecular hydrogen bonds.