Showing papers on "Steric effects published in 1978"

Steric Interaction of Fluid Membranes in Multilayer Systems

Abstract: Abstract The out-of-plane fluctuations of fluid membranes are sterically hindered in multilayer systems. The repulsive interaction associated with the steric or excluded-volume effect is studied theoretically by two methods. The interaction energy per unit area of membrane is derived as a function of temperature, membrane curvature elasticity and mean membrane spacing; it is inversely proportional to the square of the latter. Steric repulsion is estimated for lecithin bilayers in water. There and in other cases, it may compete with van der Waals attraction.

Cyclodextrin chemistry. Selective modification of all primary hydroxyl groups of α- and β-cyclodextrins

Abstract: Two efficient methods are described for the selective modification of all six primary hydroxyl groups of α-cyclodextrin (α-CD, 11). One, using an indirect strategy, involves protection of all 18 hydroxyl functions as benzoate esters, followed by selective deprotection of the six primary alcohol groups. The other, using a direct strategy, involves selective activation of the primary hydroxyl groups via a bulky triphenylphosphonium salt, which is then substituted by azide anion as the reaction proceeds. A number of modified α-cyclodextrin derivatives have been prepared and fully characterized, among which are: the useful intermediate α-cyclodextrin-dodeca (2, 3) benzoate (3); hexakis (6-amino-6-deoxy)-α-cyclodextrin hexahydrochloride (7); hexakis (6-amino-6-deoxy)-dodeca (2, 3)-O-methyl-α-cyclodextrin hexahydrochloride (9), hexa (6)-O-methyl-α-cyclodextrin (13). The direct substitution is shown to be even more efficient for β-cyclodextrin (16), giving the heptakis (6-azido-6-deoxy)-β-CD-tetradeca (2, 3)acetate (17), while the indirect strategy fails. The compounds are characterized by extensive use of 13C- and 1H-NMR. spectroscopy. The steric and statistical problems of selective polysubstitution reactions for the cyclodextrins are discussed, and possible reasons for the observed differences in reactivity between α- and β-cyclodextrins are examined. The dodecabenzoate 3 presents a very marked solvent effect on physical properties (IR. and NMR. spectra, optical rotation); the effects observed may be ascribed to an unusually strong intramolecular network of hydrogen bonds which severely distorts the α-cyclodextrin ring and lowers the symmetry from six-fold to three-fold.

Antileukemic activity of ungeremine and related compounds. Preparation of analogues of ungeremine by a practical photochemical reaction.

Abstract: A number of alkoxypyrrolophenanthridinium salts and their analogues related to the antileukemic alkaloid ungeremine were prepared by a practical photochemical cyclization. The importance of the quaternary nitrogen atom and of alkoxy groups, the planarity of a molecule, and steric considerations relative to antileukemic activity are discussed.

Intrinsic chemistry of fructose

Abstract: Studies on the mutarotation of D-fructose show that whereas the furanose-pyranose transformation is rapid, the furanose-furanose transformation is very rapid. As fructose mutarotation is found to be multiphasic at ambient temperatures, estimates of the tautomer distribution and the specific rotation of the furanose forms, by application of the unimolecular equation to optical data, are in error. Calculations from fructose tautomer shifts with temperature, and also determinations made from the invertase hydrolysis of methyl -D-fructofuranoside indicate that the specific rotation of -D-fructofuranose is +78° and that for a-D-fructofuranose is -120°. The "rules' of rotation and of anomeric specification do not therefore apply to the fructofuranoses. The saporous unit responsible for the sweet taste of -D-fructopyranose has been indentified as a tripartite grouping involving the anomeric hydroxyl group, the oxygen atom of the primary alcohol group and the ring methylene carbon atom. These represent, respectively, an appropriate proton donor (AH), and a proton acceptor (B) for an intermolecular hydrogen bonding system and also a hydrophobic bonding site (s). In the -D-fructopyranose structure they possess the proper steric disposition to elicit sweet taste. The tasteless furanose forms of fructose do not have the required steric relation between these functional groups.

Azolides. Part 12. Carbon-13 nuclear magnetic resonance study of N-methyl and N-acetyl derivatives of azoles and benzazoles

Abstract: 13 C N.m.r. chemical shifts and C–H coupling constants of methyl- and acetyl-benzazoles have been derived from data for the corresponding uncondensed azoles by addition of increments which depend on the position and nature of the azole nitrogen atoms present. Use of 13C n.m.r. parameters by estimation of conformer distribution in acetylazoles or -benzazoles proved reliable only when the individual conformers were observable. In the absence of steric effects the composition of equilibrium mixtures of isomeric N-substituted azoles is independent of the nature of the N-substituent.

Stereochemistry of multibridged, multilayered, and multistepped aromatic compounds — Transanular steric and electronic effects

Abstract: The above examples of the unique possibilities of stereo chemically fixed aromatic rings in multibridged, multilayered and multistepped hydrocarbon compounds show that these classes of compounds are most appropriate for the study of intramolecular, steric and electronic interactions, from which too little quantitative relations are known. Again, it follows that further synthetic approaches are not only possible, but also necessary for a more accurate differentiation and analysis of the frequently overlapping electronic and steric effects. More progress in this field is sure to be expected, above all when synthetic and spectroscopic chemists, and physicists adhere to interdisciplinary, collaborative work.

Substituent and steric effects in the oxidation of alkyl aryl sulfides by peroxydisulfate

Abstract: The kinetics of oxidation of a number of alkyl aryl sulfides with potassium peroxydisulfate in aqueous ethanol have been investigated. The effect of substituents on the oxidation has been studied by employing a number of p- and m-substituted phenyl methyl sulfides: the reaction is accelerated by electron-releasing and retarded by electron-withdrawing substituents, indicating a rate-determining electrophilic attack by the peroxydisulfate ion at the reaction site, sulfur. A good correlation is found to exist between the rate constants and the Hammett σ+/σ− constants, the ρ+ value for the reaction being −0.56 with a correlation coefficient of 0.979. The activation parameters have also been determined.Studies with different alkyl phenyl sulfides clearly indicate that the reaction is quite sensitive to steric congestion around the reaction site. The results obtained in this study are compared with those found for the oxidation of the same set of sulfides with different oxidants.

Conformation-reactivity relationship for pyridoxal Schiff's bases. Rates of racemization and alpha-hydrogen exchange of the pyridoxal Schiff's bases of amino acids.

Abstract: The role of stereoelectronic effects in controlhg the reaction specificity of biological reactions involving pyri- doxal phosphate-amino acid Schiff's bases was tested with nonenzymatic models. The rates of racemization and H,, ex- change of a series of pyridoxal-amino acid Schiff's bases were determined. The order of these rates does not parallel the predictions based solely on electronic or steric effect, but parallels the proportions of the reactive conformers (e.g., conformers with the C,-H, bond orthogonal to the a system) estimated by CPK models. The special reactivity of the phe- nylalanine Schiff' s base was consistent with a special confor- mation in which some type of a--a interaction increases the Pyridoxal phosphate--amino acid Schiff s bases are key in- termediates in many important biological reactions catalyzed by enzymes which require pyridoxal phosphate as a cofactor. These include transaminases, decarboxylases, synthetases, racemases, etc. (Snell & Dimari, 1970). All of these reactions are believed to proceed via cleavage of one of three bonds to C, of the amino acid. Dunathan (1966, 1971) postulated that these enzymes control the reaction specificity by controlling the conformation about the N-C, bond of the Schiff's base (SB)' intermediate. He suggested that the bond orthogonal to the a system of the SB is most easily broken due to the maximum 6-a overlap, and therefore in the enzyme active site the bond to be broken is aligned orthogonal to the P plane. Although this model was used to relate the N-C, bond conformation of the SB inter- mediates to the reaction specificity of a number of enzymes (Dunathan, 1966, 1971), it has not been adequately tested in nonenzymatic systems. However, the principle that bonds parallel to a orbitals are more labile than bonds not aligned with the a orbitals has been used to explain the 12-fold dif- ference in the rates of exchange of the axial and equatorial protons LY to a ketone group in 3/3-acetoxycholestan-7-one in the process of enolization (Corey & Sneen, 1956). This effect was attributed to stereoelectronic factors since the u electrons of the axial bond are more favorably located for overlap with the a orbital of the carbonyl group. This stereoelectronic effect has also been invoked by other workers (Hine et al., 1965) and is supported by calculations which predict maximum 6-a proportion of exchangeable conformers, thus further sub- stantiating the role of conformation in governing the reactivity of the C,,-H, bond. Furthermore, semiempirical calculations of the conformation about the C,-N bond were performed using the CAMSEA conformational analysis program. The results of conformational calculations are consistent with the results of conformational analysis by nuclear magnetic reso- nance. The order of reactivity of the C,-H, bond of the SB dianion, pH 12.0, predicted by calculation based on stereoe- lectronic effects, though not quantitatively parallel to the ob- served rate constants, is qualitatively in agreement with the experimental results.

"Tension" on heme by the proximal base and ligand reactivity: conclusions drawn from model compounds for the reaction of hemoglobin.

Abstract: The kinetic data on model compounds of hemoglobin indicate that in oxyderivatives ligand dissociation rates are sensitive to the "tension" exerted by the proximal base on the metal-to-ligand bond; the corresponding rates for carboxy derivatives are not sensitive to the tension. It is suggested that the metal-to-ligand bond becomes weaker with increased "pull" (or tension) on Fe from the proximal base due to the steric and/or electronic interaction between the ligand, the porphyrin ring, and the proximal base. In model compounds the linear heme Fe-to-CO bound vis-a-vis the bent heme Fe-to-O2 bond probably makes such interactions less significant in carboxy derivatives. It is proposed that the kinetic alpha,beta-chain nonequivalence in Hb4(O2)4 is due to the difference in the tension in the two chains on Fe by the proximal base. The absence of alpha,beta-chain differences large enough to show up in CO dissociation rates from Hb4(CO)4 is explained on the basis of lack of sensitivity of the Fe-CO bound to tension from the proximal base. The implications of the results for the observed cooperative effects in ligand combination (for CO) and dissociation (for O2 and NO) rates of hemoglobin have also been discussed.

Oxidation of heme proteins by alkyl halides: a probe for axial inner sphere redox capacity in solution and in whole cells

Abstract: Iron(II) porphyrins in homogeneous solution, in heme proteins, and in intact human erythrocytes and lysed cells are oxidized by certain alkyl halides to the corresponding iron(III) complexes at room temperature. The mechanism established for the oxidation of hemes in homogeneous solution operates at all levels of biological integrity. It is an axial inner sphere process. Deoxyhemoglobin has about the same reactivity within and without cells. The speed of the reaction with the proteins is primarily governed by the steric accessibility to iron. The reactivity of an array of iron(II) proteins accords well with theoretical prediction. In contrast the reactivity of cytochrome b5 does not. An examination of the oxidation and reduction of this protein was additional mechanistically defined reagents (trinitrobenzene and hydroquinone) shows it to be in the G rather than C conformation. The unusual redox characteristics of this protein can be rationalized on this basis.

Hydrogen-Bonded Complexes of Silica with Organic Compounds

Abstract: At ordinary temperature in water solution, labile bonds are formed between the neutral oxygen or nitrogen atoms of alcohols, ketones, ethers, amides and the hydrogen atoms of silanol groups, SiOH. The resulting Si-O-H-C hydrogen bonds are formed both in the case of the SiOH groups of polysilicic acid and with those on the surface of silica particles but apparently not with those of monosilicic acid, Si(OH)4, which is a weaker acid. Hydrogen bond formation is promoted by the presence of salt and by lower temperature, but becomes weaker above 60°C. Hydrogen bonds do not form near negatively charged −SiO− sites which increasingly populate the silica surface above pH 7. This is probably due to steric hindrance by nearby counter cations. The complexes are much more stable when many hydrogen bonds can be formed in parallel; for example, between a long polyethylene oxide molecule and the surface of a particle of colloidal silica. Phase separation occurs when a hydrophobic complex is formed and separates as a coacervate. Precipitation occurs when silica particles act as crosslinks between polymer molecules. Denaturation of protein occurs when the affinity of amide and basic nitrogen groups for the silica surface distorts the natural molecular conformation. In addition to H-bonding, certain compounds form chelate type bonds which are probably involved in the metabolism of silicon.

Carbon‐13 NMR studies of a series of benzylphenols

Abstract: Carbon-13 NMR spectra of a series of benzylphenols and their O-alkylated derivatives were recorded to find the substituent effects of the benzyl, hydroxybenzyl and alkoxybenzyl groups on the 13C chemical shifts. It was found that the methylene bridge carbons show signal shifts mainly due to the mesomeric effects of the OH and OCH3 substituents, and that in the case of ortho-substituted benzyl compounds, the methylene carbon signals exhibit upfield shifts due to both mesomeric and steric effects.