Solid and solution state conformation of 1L-1-O-acetyl-2,3:5,6-di-O-isopropylidene-chiro-inositol

The X-ray crystal structure of 1L-1-O-acetyl-2,3:5,6-di-O-isopropylidene-chiro-inositol is described. The inositol ring deviates considerably from the ideal chair conformation to a flattened chair. A comparison of its conformation in solution with that in solid was made by the use of 1H NMR. This conformational analysis revealed that the title compound adopts similar conformations in solid state and in solution states irrespective of solvent polarity.     

Solid and solution state conformations of (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-allo-inositol and (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-6-O-methyl-allo-inositol

The synthesis and conformational studies of (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-allo-inositol and (+/-)-3-O-acetyl-1,2:4,5-di-O-isopropylidene-6-O-methyl-allo-inositol are described. Solid state conformations of the title compounds have been studied by solving their X-ray crystal structures. The inositol ring in both the compounds deviate considerably from the ideal chair conformation to flattened chair conformation in the solid state. Their conformations in solution were studied by the use of 1H NMR spectroscopy. These conformational analyses revealed that the title compounds adopt similar conformations in solid and solution states irrespective of the solvent polarity.     

Crystal structure, solid state and solution conformation of 1d-1,4-di-O-[(S)-O-acetylmandeloyl]-2,3:5,6-di-O-isopropylidene-myo-inositol

The X-ray crystal structure of 1d-1,4-di-O-[(S)-O-acetylmandeloyl]-2,3:5,6-di-O-isopropylidene-myo-inositol is described. Both inositol ring and OAM (O-acetylmandeloyl) moiety deviate from their respective ideal conformations. Inositol ring adopts a flattened chair conformation while OAM adopts an ap (antiperiplanar) conformation. A comparison of its conformation in solution with that in solid was made by the use of NOESY and anisotropic shielding effect in (1)H NMR. This conformational study revealed that the title compound adopts similar conformations in both the states.     

Synthesis and structural analyses of 3-acetamido-1,4-di-O-acetyl-2,3,5-trideoxy-5-C-(isopropylphosphinyl)-D-erythro-pentopyranoses

1H NMR spectroscopy of phosphorus containing hetero sugars (phospha sugars), revealed the alpha and beta configurations and chair conformations for 3-acetamido-1,4-di-O-acetyl-2,3,5-trideoxy-5-C-(isopropylphosphinyl)-alpha- and beta-D-erythro-pentopyranoses. The conformation of the title compounds was determined by 1H NMR as 1C4 in CDCl3 and the conformation was in accord with that in solid state determined by X-ray crystallographic analysis.     

11-Demethylcyclosporins exhibit a single conformation in methanol and dimethylsulfoxide.

NMR studies showed that 11-demethylcyclosporin A (cyclosporin E) and 11-demethylcyclosporin B exist as single species both in polar and nonpolar solvents. They adopt the same conformation that was found in the solid state.     

Synthesis, characterisation and crystal structures of Schiff bases from the reaction of 4,6-O-ethylidene-beta-D-glucopyranosylamine with substituted salicylaldehydes.

Multiple chemical modifications were carried out on D-glucose to result in the corresponding Schiff bases. Such modifications performed on D-glucose not only helped in increasing the solubility of the products in nonaqueous solvents, but also restricted the anomerisation of the saccharide moiety in solution. NMR study of the products revealed the presence of the beta-anomeric form of the saccharide moiety in Me(2)SO solution. All the compounds were characterised by analytical and spectral methods. The literature is devoid of any crystal structures of saccharide-Schiff base combinations of the type reported in this paper. The crystal structures of these molecules exhibited a tridentate, ONO binding core. These studies further revealed that the compounds in the solid state were in the beta-D-pyranose form with the (4)C(1) chair conformation. The compounds exhibited interesting lattice structures assisted through weak interactions of the type O-H...O and C-H...O. The lattice structure of one of these compounds exhibited channels filled with chloroform molecules.     

Conformation of cyclo-(D-phenylalanyl-trans-4-fluoro-D-prolyl)

cyclo(D-Phenylalanyl-trans-4-fluoro-D-prolyl), c(D-Phe-D-FPro), was synthesized and its conformation determined both in solution and in the solid state by 1H NMR and X-ray analysis, respectively. In the crystals the 2.5-diketopiperazine (DKP) ring assumes the uncommon conformation, for cyclodipeptides containing Pro residue, of a flattened chair, which seemingly results from a compromise between, on the one hand, the DKP-aromatic intramolecular ring-ring attraction (folding), requiring the C alpha--C beta bond of the Phe to be axial, and, on the other hand, the intrinsic tendency of the Pro residue to have its C alpha--C beta bond equatorial. Unlike the solid state, the 1H NMR data in CDCl3 and C6D6 demonstrate that in both solutions the DKP ring assumes a boat-like shape, typical for the Pro-containing cyclodipeptides, with the equatorial C alpha--C beta bonds in both amino acid residues, which preclude ring-ring folding. A similar conformation was encountered in the closest analog of c(D-Phe-D-FPro), viz, in c(Phe-Pro), both in solution (21, 22, 26) and in the solid state (12). A subtle interplay of intramolecular interactions introduced into a cyclodipeptide by a Pro-type and a Phe-type residue is emphasized.     

Analysis of the Conformational Stability and Activity of Candida antarctica Lipase B in Organic Solvents: INSIGHT FROM MOLECULAR DYNAMICS AND QUANTUM MECHANICS/SIMULATIONS*

The conformational stability and activity of Candida antarctica lipase B (CALB) in the polar and nonpolar organic solvents were investigated by molecular dynamics and quantum mechanics/molecular mechanics simulations. The conformation change of CALB in the polar and nonpolar solvents was examined in two aspects: the overall conformation change of CALB and the conformation change of the active site. The simulation results show that the overall conformation of CALB is stable in the organic solvents. In the nonpolar solvents, the conformation of the active site keeps stable, whereas in the polar solvents, the solvent molecules reach into the active site and interact intensively with the active site. This interaction destroys the hydrogen bonding between Ser¹⁰⁵ and His²²⁴. In the solvents, the activation energy of CALB and that of the active site region were further simulated by quantum mechanics/molecular mechanics simulation. The results indicate that the conformation change in the region of active sites is the main factor that influences the activity of CALB.     

Crystal structure and solution conformation of S,S'-bis(Boc-Cys-Ala-OMe): intramolecular antiparallel beta-sheet conformation of an acyclic cystine peptide

The conformation of the acyclic biscystine peptide S,S'-bis(Boc-Cys-Ala-OMe) has been studied in the solid state by x-ray diffraction, and in solution by 1H- and 13C-nmr, ir, and CD methods. The peptide molecule has a twofold rotation symmetry and adopts an intramolecular antiparallel beta-sheet structure in the solid state. The two antiparallel extended strands are stabilized by two hydrogen bonds between the Boc CO and Ala NH groups [N...O 2.964 (3) A, O...HN 2.11 (3) A, and NH...O angle 162 (3) degrees]. The disulfide bridge has a right-handed conformation with the torsion angle C beta SSC beta = 95.8 (2) degrees. In solution the presence of a twofold rotation symmetry in the molecule is evident from the 1H- and 13C-nmr spectra. 1H-nmr studies, using solvent and temperature dependencies of NH chemical shifts, paramagnetic radical induced line broadening, and rate of deuterium-hydrogen exchange effects on NH resonances, suggest that Ala NH is solvent shielded and intramolecularly hydrogen bonded in CDCl3 and in (CD3)2SO. Nuclear Overhauser effects observed between Cys C alpha H and Ala NH protons and ir studies provide evidence of the occurrence of antiparallel beta-sheet structure in these solvents. The CD spectra of the peptide in organic solvents are characteristic of those observed for cystine peptides that have been shown to adopt antiparallel beta-sheet structures.     

Synthesis and stereochemical investigations of novel nitrogen-containing 13alpha-estrone derivatives

Novel tetrahydroquinoline 11 and N-aryl d-homo derivatives 12 in the 13alpha-estrone series were synthesized effectively, starting from the secoaldehyde 8 and mono- or disubstituted anilines 9. The chemoselectivity of the cyclization reactions depended upon the nature of the substituents in the anilines. All transformations proceeded in a highly stereoselective manner, yielding only one diastereomer. Condensed 11 and d-homo derivatives 12 both have the usual ring C chair conformation in the solid state.     

3-Amino-2-piperidinone-6-carboxylic acid. Molecular structures of cis and trans benzoyl derivatives

The cis (2a) and trans (2b) isomers of methyl 3-benzamido-2-piperidinone-6-carboxylate (Apca) were prepared and separated by fractional recrystallizations. Proton n.m.r. studies in dimethylsulfoxide solution indicate that the six-membered lactam ring adopts a distorted chair conformation with an equatorially oriented benzamido substituent in both 2a and 2b. The carboxyl function also is equatorially oriented in the trans isomer 2b, but is disposed axially in the cis isomer 2a. In the crystal structure, the six-membered lactam ring of 2a is clearly in a boat conformation with the benzamido and carboxyl functions attached to the two apex carbon atoms equatorially. The trans isomer, 2b, exists as two crystallographically independent, conformationally distinct molecules in one unit cell. The lactam ring in both molecules adopts a distorted chair conformation, as is the case in solution, with both the benazamido and carboxyl functions attached equatorially. The rotameric orientation for the endocyclic lactam differs between the two molecules. Both structures show evidence of C-H...O hydrogen bond formation intermolecularly in the solid state. This ability, along with the distinctive conformational features of Apca, may be exploitable in the design of unique features of polypeptides.     

Role of N-t-Boc group in helix initiation in a novel tetrapeptide.

Protecting groups in N- and C-terminal positions play a decisive role in the conformational preference of smaller peptides. Conformational analysis of tetrapeptide derivatives containing Ala, Ile and Gly residues was performed. Peptide 1, Boc-Ala-Ile-Ile-Gly-OMe (Boc: tert-butyloxycarbonyl) has a predominantly helical turn conformation in all the alcoholic solvents studied, whereas in the solid state it has a beta-sheet conformation. In contrast, peptide 2, Ac-Ala-Ile-Ile-Gly-OMe (Ac: acetyl) has a random coil conformation in solution. The FTIR spectrum of peptide 1 shows a lower frequency of urethane carbonyl, indicating involvement of the carbonyl group in hydrogen bonding in the helical turn.     

Nuclear magnetic resonance study of side-chain conformation of phenylalanine residue in [Met5]-enkephalin: solvent, pH, and temperature dependence.

[Met5]-Enkephalin and N-acetylphenylalanine methylamide containing (2S,3S)-[2,3-2H2]Phe were synthesized 270 MHz 1H NMR spectra of the normal and selectively deuterated species were analysed. The lower-field and higher-field beta-proton signals of the Phe4 residue of [Met5]-enkephalin were unambiguously assigned to the pro-S and pro-R protons, respectively. The same assignments apply to N-acetylphenylalanine methylamide in polar organic solvents and in 2H2O, but the alternative assignments apply in C2HCl3. For [Met5]-enkephalin, the vicinal spin coupling constants 3JalphabetaS and 3 JalphabetaR and the rotamer populations around the Calpha-Cbeta bond were determined in a variety of solvents. From the pH and temperature dependences of rotamer populations of [Met5]-enkephalin, the side-chain conformation of the Phe residue in 2H2O solution was found to be considerably different from that in (C2H3)2SO solution. Rotamer populations of the Phe4 residue of [Met5]-enkephalin in organic solvents depend on solvent polarity. As compared with the reference model molecule of N-acetylphenylalanine methylamide, the rotamer populations of Phe4 of [Met5]-enkephalin are affected possibly by steric repulsion with other residues; the rotamer I is primarily favored but the rotamer II is appreciably destabilized in weakly polar solvents.     

Solid-state 13C NMR and X-ray diffraction of dermatan sulfate

Dermatan sulfate in the solid state has been studied by 13C CP/MAS nmr and X-ray diffraction in order to establish the ring conformation of the L-iduronate moiety. The solid state nmr spectrum is similar to the solution spectrum obtained previously, indicating that a ring conformation at least approximating to 1C4 predominates in the solid state. X-ray powder diffraction data from the same sample indicate the presence of the 8-fold helix form previously observed by fiber diffraction, and interpreted in terms of a 4C1 ring form. A likely explanation of the results is that a distorted 1C4 L-iduronate ring conformation, not considered in the initial X-ray analysis, may emerge to provide a satisfactory interpretation of all available physical-chemical data.     

Protein structure, stability and solubility in water and other solvents

Proteins carry out the most difficult tasks in living cells. They do so by interacting specifically with other molecules. This requires that they fold to a unique, globular conformation that is only marginally more stable than the large ensemble of unfolded states. The folded state is stabilized mainly by the burial and tight packing of over 80% of the peptide groups and non-polar side chains. If life as we know it is to exist in a solvent other than water, the folded state must be stable and soluble in the new solvent. Our analysis suggests that proteins will be unstable in most polar solvents such as ethanol, extremely stable in non-polar solvents such as cyclohexane, and even more stable in a vacuum. Our solubility studies suggest that protein solubility will be markedly lower in polar solvents such as ethanol and that proteins will be essentially insoluble in non-polar solvents such as cyclohexane. For these and other reasons it seems unlikely that the life we know could exist in any solvent system other than water.     

Solid state and solution conformation of Boc-L-Met-Aib-L-Phe-OMe. Beta-turn conformation of a sequence related to an active chemotactic peptide analog

The conformation of the peptide Boc-L-Met-Aib-L-Phe-OMe has been studied in the solid state and solution by X-ray diffraction and 1H n.m.r., respectively. The peptide differs only in the N-terminal protecting group from the biologically active chemotactic peptide analog formyl-L-Met-Aib-L-Phe-OMe. The molecules adopt a type-II beta-turn in the solid state with Met and Aib as the corner residues (phi Met = -51.8 degrees, psi Met = 139.5 degrees, phi Aib = 58.1 degrees, psi Aib = 37.0 degrees). A single, weak 4----1 intramolecular hydrogen bond is observed between the Boc CO and Phe NH groups (N---O 3.25 A, N-H---O 128.4 degrees). 1H n.m.r. studies, using solvent and temperature dependencies of NH chemical shifts and paramagnetic radical induced line broadening of NH resonances, suggest that the Phe NH is solvent shielded in CDCl3 and (CD3)2SO. Nuclear Overhauser effects observed between Met C alpha H and Aib NH protons provide evidence of the occurrence of Met-Aib type-II beta-turns in these solvents.     

A Raman spectroscopic study of hen egg yolk phosvitin: structures in solution and in the solid state

Laser Raman spectroscopy has been employed to study the structure of the hen egg yolk protein phosvitin in H2O and D2O solutions at neutral and acidic pH (pD) and in the solid state. The Raman data indicate an unusual conformation for phosvitin in neutral aqueous solution, which is deficient in both alpha-helix and conventional beta-sheet conformations. This unusual pH 7 structure is, however, largely converted to a beta-sheet conformation in strongly acidic media (pH less than 2). beta-Sheet is also the predominant secondary structure for phosvitin in the solid state, obtained by lyophilization of the protein from aqueous solution at neutral pH. The imidazolium rings of histidyl residues remain significantly protonated near neutrality, which suggests substantial elevation of the pK for imidazolium ring ionizations of phosvitin in aqueous solution. This may result from extensive ion-pair interactions involving positively charged histidines and negatively charged phosphoserines, which are prevalent in the phosvitin sequence. The present results suggest that antiparallel beta-sheets may not be the secondary structure most characteristic of native phosvitin (physiological pH), even though beta-sheet is the predominant conformation for phosvitin in acidic solutions (pH 1.5) and in the lyophilized solid. Phosvitin appears to be the first protein for which the major component to the Raman amide I band is centered near 1685 cm-1, which is 10-40 cm-1 higher than proteins heretofore examined in aqueous solution by Raman spectroscopy.     

NMR spectroscopy: a powerful tool for detecting the conformational features of symmetrical persubstituted mixed cyclomaltoheptaoses (beta-cyclodextrins)

The conformation in solution of exhaustively derivatized mixed cyclomaltooligosaccharides (cyclodextrins) has been defined by NMR spectroscopy. Both tilting of glucopyranose units about the glycosidic linkages and ring deviations from the 4C1 chair conformation are detected, the entities of which are strongly dependent on the nature of the derivatizing groups.     

Utilization of tannery solid waste for protease production by Synergistes sp. in solid‐state fermentation and partial protease characterization

Synergistes sp. DQ560074 produced a protease in submerged fermentation (SmF) at 400–420 U/mL and in solid‐state fermentation (SSF) at 745–755 U/g. The protease, which belongs to the aspartic protease class, was active over a wide range of pH (5–7) and at high temperatures (25–45°C). The protease is stable and active in various polar protic solvents (50% v/v) like ethanol, isopropanol, n–butanol, in polar aprotic solvents (50% v/v) like acetonitrile, and in non‐polar solvents (50% v/v) such as ethylacetate and toluene, but not in hydrophilic organic solvents (methyl alcohol and acetone). As far as we know, this is the first contribution to the production of a mesophilic protease with solvent stability in SSF using a proteinaceous solid waste.     

Synthesis and conformation of four 16,17-diols in the 3-methoxy-13alpha-estra-1,3,5(10)-triene series

All four diasteromeric 16,17-diols in the 3-methoxy-13alpha-estra-1,3,5(10)-triene series have been synthesized. The trans-diols 1 and 2 can be obtained by hydroborating the 17-enol acetate 6 (61%, ratio 27:73, preferred alpha attack). OsO(4) dihydroxylation of the olefin 7 yielded the cis-diols 3 and 4 (ratio 13:87). The dihydroxylation proceeds with preference for beta attack caused by a C-ring twist-boat form of 7. The conformations of the diols 2 and 4, the 17-benzyl-17-hydroxy compounds 9 and 10 (obtained by Grignard reaction), and the 16alpha-bromo-17beta-hydroxy compound 8 were determined by X-ray analysis and by 1H NMR spectroscopy in solution. Some compounds, in spite of a 17beta-hydroxy group, had a conformation with a ring C chair form (4, 8, 9) caused by intermolecular interaction in the solid state. The rest of the compounds studied here (2, 10) possessed a conformation with a ring C twist-boat form, which has been also found for all 17beta-substituted compounds in solution. The preferred conformation of the D-ring with 17beta-substituents seems to be the 16beta-envelope form or near this form, but the existence of the 16alpha-envelope form (inversion of the ring D) for some compounds showed great variance in the conformation of ring D, which is substituent dependent.