Showing papers on "Steric effects published in 1992"

Sol-gel chemistry

Abstract: Sol-gel chemistry involves nucleophilic reactions The chemical reactivity of metal alkoxides toward hydrolysis, condensation and complexation mainly depends on the electronegativity of the metal atom, its coordination number and the steric hindrance of alkoxide groups Silicon alkoxides are poorly reactive Hydrolysis and condensation rates have to be enhanced by acid and base catalysis or nucleophilic activation Transition metal alkoxides are usually too reactive They have to be stabilized by complexation in order to avoid fast condensation The molecular design of alkoxide precursors opens the way to tailor-made materials

Crystal structure of the major histocompatibility complex class I H-2Kb molecule containing a single viral peptide: implications for peptide binding and T-cell receptor recognition.

Abstract: To study the structure of a homogenous major histocompatibility complex (MHC) class I molecule containing a single bound peptide, a complex of recombinant mouse H-2Kb, beta 2-microglobulin (beta 2m), and a fragment of the vesicular stomatitis virus (VSV) nuclear capsid protein, VSV-(N52-59) octapeptide (Arg-Gly-Tyr-Val-Tyr-Gln-Gly-Leu), was prepared by exploiting a high-yield bacterial expression system and in vitro cocomplex formation. The structure of mouse H-2Kb revealed its similarity to three human class I HLA molecules, consistent with the high primary sequence homology and common function of these peptide-presenting molecules. Electron density was located in the peptide-binding groove, to which a single peptide in a unique conformation was unambiguously fit. The peptide extends the length of the groove, parallel to the alpha-helices, and assumes an extended, mostly beta-strand conformation. The peptide is constrained within the groove by hydrogen bonding of its main-chain atoms and by contacts of its side chains with the H-2Kb molecule. The amino-terminal nitrogen atom of the peptide forms a hydrogen bond with the hydroxyl group of Tyr-171 of H-2Kb at one end of the groove, while the carboxyl-terminal oxygen forms a hydrogen bond with the hydroxyl group of Tyr-84 at the other end. Since the amino acids at both ends are conserved among human and mouse MHC molecules, this anchoring of each end of the peptide appears to be a general feature of peptide-MHC class I molecule binding and imposes restrictions on its length. The side chains of residues Tyr-3, Tyr-5, and Leu-8 of the VSV octapeptide fit into the interior of the H-2Kb molecule with no appreciable surface exposure, a finding in support of previous biological studies that showed the importance of these residues for binding. Thus, the basis for binding of specific peptide sequences to the MHC class I molecule is the steric restriction imposed on the peptide side chains by the architecture of the floor and sides of the groove. The side chains of Arg-1, Val-4, and Gln-6 and the main-chain of Gly-7 of the octapeptide are exposed on the surface of the complex, thus confirming their availability for T-cell receptor contact, as previously demonstrated by T-cell recognition experiments.

Topological properties of electron density in search of steric interactions in molecules: electronic structure calculations on ortho-substituted biphenyls

Abstract: The bond critical points in the electron density are not necessarily associated with bonding interactions. When the distance between two atoms is smaller than their contact interatomic separation (CIS), an attractor interaction line passing through the corresponding bond critical point appears, indicating a nonbonding repulsive interaction. Sterically crowded molecules are defined as those possessing such interaction lines at their equilibrium geometries

Central Bond in the Three CN• Dimers NC–CN, CN–CN and CN–NC: Electron Pair Bonding and Pauli Repulsion Effects

Abstract: The strength of the CN/CN' bond decreases in the series NC-CN (1), CN-CN (2), and CN-NC (3), while simultaneously it shortens. The explanation requires that, apart from the σ pair bond between the CN 5σ MO's, the following effects be taken into account: (a) Pauli repulsion («steric hindrance») between the 4σ («N lone pair») orbitals; (b) Pauli repulsion between the 4σ and 5σ orbitals; (c) donor/acceptor interaction between the 4σ and 5σ orbitals; (d) donor/acceptor interaction between the occupied 1 π and unoccupied 2π *

Tris(trimethylsilyl)silane: an efficient hydrosilylating agent of alkenes and alkynes

Abstract: tris(trimethylsilyl)silane adds across the double bond of a variety of mono-, di-, and trisubstituted under free-radical conditions in good yields. The reaction, which proceeds via a free-radical chain mechanim, is highly regioselective (anti-Markovnikov). Addition to prochiral olefins bearing an ester group is highly stereoselective. The factors that control the stereochemistry have been discussed in term of preferred conformations of the intermediate carbon-centered radicals and are thought to be of steric origin

A predictive model for substrates of cytochrome P450-debrisoquine (2D6).

Abstract: Molecular modeling techniques were used to derive a predictive model for substrates of cytochrome P450 2D6, an isozyme known to metabolize only compounds with one or more basic nitrogen atoms Sixteen substrates, accounting for 23 metabolic reactions, with a distance of either 5 A ("5-A substrates", eg, debrisoquine) or 7 A ("7-A substrates", eg, dextromethorphan) between oxidation site and basic nitrogen atom were fitted into one model by postulating an interaction of the basic nitrogen atom with a negatively charged carboxylate group on the protein This acidic residue anchors and neutralizes the positively charged basic nitrogen atom of the substrates In case of "5-A substrates" this interaction probably occurs with the carboxylic oxygen atom nearest to the oxidation site, whereas in the case of "7-A substrates" this interaction takes place at the other oxygen atom Furthermore, all substrates exhibit a coplanar conformation near the oxidation site and have negative molecular electrostatic potentials (MEPs) in a part of this planar domain approximately 3 A away from the oxidation site No common features were found in the neighbourhood of the basic nitrogen atom of the substrates studied so that this region of the active site can accommodate a variety of N-substituents Therefore, the substrate specificity of P450 2D6 most likely is determined by the distance between oxidation site and basic nitrogen atom, by steric constraints near the oxidation site, and by the degree of complementarity between the MEPs of substrate and protein in the planar region adjacent to the oxidation site(ABSTRACT TRUNCATED AT 250 WORDS)

Distorted molecules : perturbation design, preparation and structures

Abstract: The structure of a molecule can change considerably as its energy and thus its electron distribution within the time-domain of dynamic relaxation varies. Based on comparison of approriate measured data of related compounds and supported by quantum chemical calculations, therefore, charge-perturbed and/or sterically overcrowded molecules can be designed. Their preparation, handling, and structural characterization, frequently under extreme and especially largely aprotic conditions, provides some surprises. New structural principles become evident and old-fashioned ones are confirmed. Thus the contact-ion aggregates that form on ultrasonically supported reduction of unsaturated hydrocarbons with sodium metal partly contain dibenzene sodium sandwiches. Vicinal dimethylamino substituents or isoelectronic isopropyl groups cause steric overcrowding and facilitate oxidation to molecular cations by energetically favorable delocalization of the generated positive charge. Molecules and molecular ions in which an even number of π electrons are distributed over a σ skeleton containing an odd number of centers preferentially form cyanine subunits. This is demonstrated by the novel ethene dication and dianion salts with central CC single bonds and molecular halves twisted relative to each other. Altogether in two years well over 50 structures have been determined. Much has been learned from them, especially about electron transfer and contact ion-pair formation in aprotic solvents. Nevertheless, we had to realize that answers to many questions, above all “what crystallizes, how, and why”, are still out of reach.

A molecular mechanics model of ligand effects. 3. A new measure of ligand steric effects

Abstract: Molecular mechanics methods have been employed to compute energy-minimized structures for a large number of Cr(CO) 5 L complexes, where L is CO, triarylphosphine, mixied trialkyl/arylphosphine, phoshine, alkyl/aryl/alkoxyphosphine, or one of 8 analogous arsenic ligands. The energy-minimized structures are employed to compute a new mesure of ligand steric effect, the ligand repulsive energy E R , obtained by computing the van der Waals repulsive force acting between the ligand

Definition and display of steric, hydrophobic, and hydrogen-bonding properties of ligand binding sites in proteins using Lee and Richards accessible surface: validation of a high-resolution graphical tool for drug design.

Abstract: The accessible surface, described by Lee and Richards (the L&R surface: J. Mol. Biol. 1971, 55, 379), has remarkably useful properties for displaying ligand-protein interactions. The surface is placed one van der Waals radius plus one probe radius away from the protein atoms. The ligands are displayed in skeletal form. With a suitable probe radius, those parts of the ligand in good van der Waals contact with the protein binding site are found superimposed on the L&R surface. Display of the surface using parallel contours therefore provides a very powerful guide for interactive drug design because only ligand atoms lying on or close to the surface are in low-energy contact. The ability of the surface to accurately display steric complementarity between ligands and proteins was optimized using data from small molecule crystal structures. The possibility of displaying the chemical specificity of the binding site was also investigated. The surface can be colored to give precise information about chemical specificity. Electrostatic potential, electrostatic gradient, and distance to hydrogen-bonding groups were tested as methods of displaying chemical specificity. The ability of these methods to describe the complementarity actually observed in the interior of proteins was compared. High-resolution crystal data for ribonuclease and trypsin was used. The environment surrounding extended peptide chains in the protein was treated as a virtual binding site. The peptide chain served as a virtual ligand. This large sample of experimental data was used to measure the correlation between type of ligand atom and the calculated property of the nearest binding site surface. The best correlation was obtained using hydrogen-bonding properties of the binding site. Using this parameter the surface could be divided into three separate zones representing the hydrophobic, hydrogen-bond-acceptor, and hydrogen-bond-donor properties of the binding site. The percentage of hydrophobic ligand atoms found to lie closest to the hydrophobic protein surface was 91%. The equivalent scores for ligand hydrogen-acceptor atoms and hydrogen-donor atoms found at the corresponding complementarity zone were 94% and 91%. The surface zones can be readily displayed using three colors. To test the method on real ligand/binding site interactions, nine thermolysin-inhibitor complexes of known structure were evaluated using the parameters and criteria derived from the protein-packing study and a correlation between complementary contacts and logarithm of potency was obtained which had an r2 of 0.99.(ABSTRACT TRUNCATED AT 400 WORDS)

Absolute configuration of bilirubin conformational enantiomers

Abstract: Bilirubin, the yellow pigment of jaundice, is a bichromophoric tetrapyrrole formed in mammals by heme catabolism. It readily adopts either of two enantiomeric folded conformations which are shaped like ridge tiles and are stabilized by a network of intramolecular hydrogen bonds. Interconversion of the conformational enantiomers is rapid at room temperature and may bc displaced toward either enantiomer by complexation with chiralagents. Intramolecular steric effects may also affect enantioselection

Diastereofacial Selectivity in Reactions of Substituted Cyclohexyl Radicals. An Experimental and Theoretical Study

Abstract: The diastereofacial selectivity in reactions of a series of alkyl-substituted cyclohexyl radicals has been investigated. In additions of cyclohexyl radicals to alkenes, it has been found that only substituents bound at the olefinic center being attacked by the radical influence the equatorial-axial selectivity. Substituents bound to the radical center or axial substituents p to the radical center lead to increased axial attack. Equatorial /3-substituents or axial ?-substituents increase the amount of equatorial attack. The same trends are observed for halogen and hydrogen abstraction reactions; the amount of axial reaction product is usually somewhat higher than in the addition reactions. The stereoselectivities can be explained with steric and torsional effects very similar to those suggested for nucleophilic addition reactions to cyclohexanones. A MM2 force field has been parameterized to gain further insight into the stereochemistry of the reaction.

Ligand effects associated with the intrinsic selectivity of DNA oxidation promoted by nickel(II) macrocyclic complexes

Abstract: Nickel(II)-promoted oxidation of accessible guanine residues in deoxyoligonucleotides using KHSO 5 as oxidant was found to be highly dependent upon the macrocyclic ligand employed. Systematic structural variations of the ligands Me 2 [14]py-dieneN 4 (CR) and [14]aneN 4 (cyclam) have provided information about the importance of ring size, degree of unsaturation, steric bulk, redox potential, in-plane ligand field strength, and conformational flexibility in determining DNA reactivity with a 17-base hairpin oligonucleotide

Influence of strain on chemical reactivity. Relative reactivity of torsionally distorted double bonds in MCPBA epoxidations

Abstract: The second-order reaction rata were measured for the MCPBA epoxidation in CH 2 Cl 2 for a series of cyclic olefins including bridgehead olefins and trans-cycloalkenes. As expected, strained bridgehead alkenes and trans-cycloalkenes showed faster reaction rates than nonstrained cis-cycloalkenes. The MM-2 steric energies of alkenes, alkanes, and their corresponding epoxides were calculated to evaluate the strain energy released in each reaction (ΔSE). Plots of log k rel vs olefin strain didnot show a good correlation

Conformational analysis of trehalose disaccharides and analogues using MM3

Abstract: Energy surfaces for the relative orientations of the pyranosyl rings of α,α‐, α,β‐, and β,β‐trehalose and analogues were generated with MM3. Sixteen starting conformations of the rotatable side groups of α,β‐trehalose were considered, while only 10 conformations were needed for α,α‐ and β,β‐trehalose because of molecular symmetry. Energies were calculated at 20° increments of the two torsional angles of the glycosidic linkage, but otherwise the molecules were fully relaxed. The structure at the overall minimum for α,α‐trehalose agrees well with that found in crystal structures, and also agrees with interpretations of NMR and optical rotation data. The energy surfaces for the three trehaloses differ greatly from each other, but are each similar to those for the corresponding three 2‐(6‐methyltetrahydropyran‐2‐yloxy)6‐methyltetrahydropyrans. This suggests that linkage type (axial or equatorial) is more important than exocyclic substituents in determining trehalose conformations. A comparison with surfaces from the corresponding 5a‐carba trehalose analogues illustrates that the exo‐anomeric effect is important in determining disaccharide conformation.

Design, synthesis, and conformational analysis of a novel spiro-bicyclic system as a type II β-turn peptidomimetic

Abstract: A novel highly constrained spiro-bicyclic system (5) has been developed to mimic the type II β-turn, a secondary structural feature found in many bioactive peptides. This system simultaneously restricts three (Φ 2 , Ψ 2 , and Φ 3 ) of the four torsion angles that characterize the type II β-turn. As a test of the design, the asymmetric synthesis and conformational analysis of derivative 6 starting from (R)-2-allylproline is reported. Temperature dependent NMR chemical shift studies in CDCl 3 suggest that the amide proton of 6 is involved in an intramolecular hydrogen bond.Aso,NOE measurements place this hydrogen under the plane of the bicyclic ring system in proper proximity for this hydrogen bond to form with the acetyl carbonyl oxygen.Modeling studies of 6 produced eight minimum-energy conformations with torsion angles close to those of the classical type II β-turn.A comparison of the minimum-energy conformer of this molecule with the classical type II β-turn gave an RMS fit=0.161 A °

Photophysics of halogenated porphyrins

Abstract: A series of free-base octaalkylporphyrins having halogen substituents at different sites on the nucleus has been examined by photophysical methods. In general, halogenation decreases the fluorescence yield and lifetime, increases triplet formation and decreases the resultant triplet lifetime. The magnitude of these effects, which increases in the order F < Cl < Br < I and is dependent on the site of halogenation (benzylic position of alkyl < β position of pyrrole < meso position) can be explained in terms of a modified spin–orbit coupling theory. Multiple halogenation at meso positions, however, can cause secondary effects, due to steric crowding (bromine) or electron redistribution (fluorine). Photophysical data derived from the full set of meso-fluorinated porphyrins can be described quantitatively in terms of combined spin–orbit coupling and electronic perturbation in which a fluorine substituent deactivates adjacent meso sites but activates the site opposite the substituent.

Formation and reactivity of (tetraarylporphyrinato)rhodium(II) monocarbonyls: bent RhIICO complexes that react like acyl radicals

Abstract: Reactions for a series of rhodium(II) porphyrins with CO are used in illustrating the use of ligand steric effects in both promoting and inhibiting CO coupling to form α-diketone complexes ((por)RhC(O)C(O)Rh(por))

The role of Lewis acid-base processes in ligand-exchange chromatography of benzoic acid derivatives on zirconium oxide.

Abstract: Porous microparticulate zirconium oxide shows very different selectivities and pH dependencies for the separation of benzoic acid derivatives than do conventional bonded-phase anion-exchange supports This results from a very significant ligand-exchange contribution to the retention of hard Lewis bases on the surface of transition-metal oxide supports We have found that the capacity factors of a wide variety of derivatives of benzoic acid are closely correlated with their Bronsted acidities The eluent pH is also a critical factor in determining the magnitude of the capacity factor, but it does not have much influence on chromatographic selectivity The differential selectivity of this phase in comparison to conventional polymeric and bonded-phase anion exchangers can be attributed to complexation and steric effects which profoundly alter the elution patterns of certain solutes

Photoinduced electron transfer in linked ruthenium(II) diimine-diquat complexes: Linkage dependence

Abstract: Intramolecular photoinduced electron transfer in a series of linked ruthenium(II) diimine donor-diquat acceptor complexes was examined as a function of the nature of the bridge between the donor and acceptor centers. Bridging groups include polymethylene chains (-(CH{sub 2}){sub n-}, n=2-7,12) and phenyl- or cyclohexyl-containing spacers (p-(-CH{sub 2}-Ph-CH{sub 2}-), p-(-CH{sub 2}-trans-cyclohexyl-CH{sub 2}-), and p-(-CH{sub 2}-cis-cyclohexyl-CH{sub 2}-)). The rate constant for electron transfer decreases sharply as the number of methylenes separating the donor and acceptor increases in straight chain alkyl bridged complexes. An odd-even alternation in the electron-transfer rate constant is observed in the straight chain series. Rate constants for electron transfer in the series of complexes bridged by the cyclic spacers having a fixed number of bonds but differing steric environments varied by only a factor of 2. Results are discussed in terms of possible through-space and through-bond interactions. The combined results suggest that the bridging ligands may serve to mediate the electron transfer in these systems. 49 refs., 7 figs., 3 tabs.

Development of an eluotropic series for the chromatography of Lewis bases on zirconium oxide.

Abstract: Ligand-exchange interactions, which dominate the retention characteristics of Lewis base solutes on zirconium oxide, can be strongly attenuated by the addition of a competing Lewis base to the eluent. The chromatographic effects of these competing bases vary significantly in their thermodynamics and kinetics depending on their structure and Lewis basicity. An eluotropic scale of mobile-phase strength for ligand-exchange/ion-exchange chromatography on zirconia has been developed which ranks the overall elution strength of a variety of Lewis bases in terms of their ability to elute a wide variety of benzoic acid derivatives. This series generally holds true for similar solutes; however, deviations are noted with some solutes and eluents where chelation and steric factors alter the kinetic and thermodynamic characteristics of the retention process.

Conformation and reactivity of anomeric radicals

Abstract: Reductive decyanations of 2-cyanotetrahydropyran derivatives with sodium in ammonia show a strong preference for axial protonation. For the 2-cyanotetrahydropyran 6, the selectivity is 119:1, and for the cyanooxadecalin 13, which is sterically biased against axial hydrogen introduction, the ratio is 1.78:1. These stereochemical outcomes and ab initio calculations of the intermediate radical conformations are consistent with the following mechanistic model: reductive decyanation proceeds through the pyramidal, axial radical to give the configurationally stable, contrathermodynamic axial anion which is protonated with retention of configuration

Phosphorus derivatives of anthracene and their dimers

Abstract: The syntheses of the (9-anthracenyl)phosphanes 2 to 7 and of the metal carbonyl complexes 8 and 9 are described. Both 1 and 4 undergo [4 + 4] cycloaddition when irradiated, forming the dimers 10 and 11. Only one of the six possible rotamers for 10 is formed. For 11 one additional rotational isomer is observed. The relationship between the [4 + 4] dimerization and steric effects of the PR2 group is discussed. The compounds 6, 8 and 11 were characterized by X-ray diffraction. The structure of 6 was rendered imprecise by the presence of disordered toluene, but the influence of the bulky anthracenyl groups was clear, with wide CPC angles of 110.4°. The molecule displays imposed threefold symmetry. The two independent molecules of complex 8, which crystallizes as a dichloromethane hemisolvate, are closely similar to each other; the WP bond lengths are 254.3 and 253.4 pm. The WC bonds trans to phosphorus are 4 pm shorter than those cis. The phosphane dimer 11 crystallizes with imposed centrosymmetry. The H atom positions, which could be tentatively identified from difference syntheses, indicate a different rotamer than was formed for the analogous fluorophosphane dimer 10.