Complex carbohydrates: 1. Conformational studies on some oligosaccharides related to N-glycosyl proteins which interact with concanavalin A

Empirical potential energy calculations have been carried out to determine the preferred conformations of some oligosaccharides having the trimannosidic core structure (Man3GlcNAc2) and which interact with concanavalin A. In the minimum energy conformations for the trimannosidic core the mannose residue on the Man α(1–6) arm comes close to one of the N-acetylglucosamine residues of the core. The addition of N-acetylglucosamine residues to the terminal mannose residues does not alter the preferred conformation of the trimannosidic core although it alters the relative preference of some of the higher energy conformations. The minimum energy conformation broadly agrees with available X-ray data. The presence of a bisecting N-acetylglucosamine residue on the middle mannose does not push the trimannosidic core to any new conformation but it does alter the relative preference for a particular conformation.

Self-assembly of a Pd-II neutral molecular rectangle via a new organometallic Pd-2(II) molecular clip and oxygen donor linker

Two components self-assembly of a Pd-4 neutral molecular rectangle driven by Pd-O bond coordination has been achieved and this pi-electron rich rectangle shows fluorescence quenching in presence of nitroaromatics, which are the chemical signatures of many explosives.

Polymorphism and conformational flexibility of DNA: right and left handed duplexes

Left handed duplexes are shown to be in agreement with the X-ray intensity data of A-, B- and D-forms of DNA. The structures are stereochemically satisfactory because they were obtained following a stereochemical guideline derived from theory and single crystal structure data of nucleic acid components. The same stereochemical guideline also led to right handed duplexes for B- and D-forms of DNA which have stereochemically preferred conformation and hence are superior to those given by Arnott and coworkers.

The Crystal Structure of Pivaloyl- D- prolyl-L- prolyl- L-alanyl-N- methylamide

Pivaloyl-D-prolyl-L-prolyl-L-analyl-N-methylam~de (I), C1UH32N40c4r,y stallizes in the orthorhombic space group P21212,w ith four molecules in a unit cell of dimensions a = 9.982 (l),b = 10.183 (3), c = 20.746 (2)A . The structure has been refined to R 0.048 for 1 745 observed reflections. All the peptide bonds in the molecule are trans and both the prolyl residues are in the CY-exo-conformation. The molecule assumes a highly folded conformation in which a Type II' DL bend is followed by a Type I LL bend, both stabilised by intramolecular 4 + 1 hydrogen bonds. This conformation, which has been observed for the first time, is of interest in relation to the structure of gramicidin S.

Crystal and molecular structures of alkali- and alkaline-earth-metal complexes of N,N-dimethylformamide

Structures of lithium, sodium, magnesium, and calcium complexes of NJ-dimethylformamide (DMF) have been investigated by X-ray crystallography. Complexes with the formulas LiCl.DMF.1/2H20, NaC104.2DMF, CaC12.2DMF.2H20, and Mg(C104)2.6DMF crystallized in space groups P2]/c, P2/c, Pi, and Ella, respectively, with the following cell dimensions: Li complex, a = 13.022 (7) A, b = 5.978 (4) A, c = 17.028 (10) A, = 105.48 (4)O, Z = 8; Na complex, a = 9.297 (4)A, b = 10.203 (3) A, c = 13.510 (6) A, /3 = 110.08 (4)O, Z = 4; Ca complex, a = 6.293 (4) A, b = 6.944 (2) A, c = 8.853(5) A, a = 110.15 (3)O, /3 = 105.60 (6)", y = 95.34 (5)", Z = 1; Mg complex, a = 20.686 (11) A, b = 10.962 (18) A,c = 14.885 (9) A, /3 = 91.45 (5)O, Z = 4. Lithium is tetrahedrally coordinated while the other three cations are octahedrally coordinated; the observed metal-oxygen distances are within the ranges generally found in oxygen donor complexes of these metals. The lithium and sodium complexes are polymeric, with the amide and the anion forming bridging groups between neighboring cations. The carbonyl distances become longer in the complexes accompanied by a proportionate decrease in the length of the central C-N bond of the amide; the N-C bond of the dimethylamino group also shows some changes in the complexes. The cations do not deviate significantly from the lone-pair direction of the amide carbonyl and remain in the amide plane. Infrared spectra of the complexes reflect the observed changes in the amide bond distances.

A circular dichroism study of (+) gossypol binding to proteins

The circular dichroism bands of (+) gossypol in the spectral region 300–400 nm have been shown to be sensitive to interactions with proteins. Using CD spectroscopy, gossypol has been shown to interact with lactate dehydrogenase, malate dehydrogenase, alkaline phosphatase, lysozyme, protamine and poly-L-lysine. Binding to proteins generally results in a pronounced red shift of the long wavelength CD band (not, vert, similar 380–430 nm) accompanied by a reduction in ellipticity. The changes in spectral parameters of the 1Lb binaphthyl transtion may reflect a distortion from a nearly perpendicular gossypol conformation, on binding to proteins.

Theoretical-Studies On The Conformations Of Acyclic Alditols

The conformational analysis by energy calculation is described for some acyclic sugars such as D-glucitol, D-mannitol and galactitol. Planar Zig-zag conformation is the most favoured conformation for the three alditols. However, the energy difference between the ‘bent-chain’ and ‘straight-chain’ conformation is less in the case of D-glucitol (0.9 Kcal Mole-1)compared to those of D-mannitol (~2.4 Kcal mole-1)and galactitol (~2.5 Kcal Mole-1).The solvent accessibility studies favour bent –chain conformation for D-glucitol and straight-chain conformation for D-mannitol and glactitol. These conformations, arrived at by theorticle analysis are compared with those abseverd in the solid state determined by X=ray differaction techinique and their acetylated derivatives in solution by NMR technique. These studies suggest that, when the energy difference between straight and bent conformations is small, latticc energy (in the case of solids) and solvent (in the case of solutions) do play a dominant role on the favoured conformations.

Solvent effects on the structure of N-methylpyrrole as studied by nmr in nematic solvents

The proton NMR spectra of N-methylpyrrole oriented in the nematic phases of liquid crystals with positive and negative diamagnetic anisotropies and their mixtures are reported. Geometrical parameters derived from the spectra at the critical point in the mixture of liquid crystals with positive and negative diamagnetic anisotropies, where macroscopic diamagnetic anisotropy vanishes, are similar to those obtained in the solvent with negative diamagnetic anisotropy. However, significant distortions in the molecular structure attributed to solvent effects have been observed in liquid crystals with positive diamagnetic anisotropy. The minimum energy conformation has one C---H of the methyl perpendicular to the ring.

Theoretical studies on Beta-lactam antibiotics VI: Conformational analysis and structure-activity relationships of penicillin sulfoxides and cephalosporins

Conformational energy calculations were carried out on penicillin α-and Β-sulfoxides and δ2- and δ3-cephalosporins, in order to identify the structural features governing their biological activity. Results on penicillin Β-sulfoxide indicated that in its favoured conformation, the orientation of the aminoacyl group was different from the one required for biological activity. Penicillin α sulfoxide, like penicillin sulfide, favoured two conformations of nearly equal energies, but separated by a much higher energy barrier. The reduced activity of the sulfoxides despite the nonplanarity of their lactam peptide indicated that the orientations of the aminoacyl and carboxyl groups might also govern biological activity. δ3-cephalosporins favoured two conformations of nearly equal energies, whereas δ2-cephalosporins favoured only one conformation. The lactam peptide was moderately nonplanÄr in the former, but nearly planar in the latter. The differences in the.preferred orientations of the carboxyl group between penicillins and cephalosporins were correlated with the resistance of cephalosporins to penicillinases.

Structure and conformation of an anti-depressant drug, nitroxazepine hydrochloride monohydrate

CIsH20N3Oa+.C1-.H2 O, M r = 395, orthorhombic, Pn21a, a = 7.710 (4), b = 11.455 (3), c -- 21.199 (3)/k, Z = 4, V = 1872.4/k 3, D m = 1.38, D C = 1.403 g cm -3, F(000) = 832, g(Cu Kct) = 20.94 cm -l. Intensities for 1641 reflections were measured on a Nonius CAD-4 diffractometer; of these, 1470 were significant. The structure was solved by direct methods and refined to an R index of 0.045 using a blockdiagonal least-squares procedure. The angle between the least-squares planes through the benzene rings is 125.0 (5) ° and the side chain is folded similarly to one of the independent molecules of imipramine hydrochloride.

Is 3'-nucleotide rigid?

Conformational analysis of nucleic acids and polynucleotides is far more complex than that of proteins and polypeptides, due to five single bond rotations in addition to the sugar puckerings in the monomer. Sundaralingam1 proposed the concept of the 'rigid' nucleotides from analysis of crystal structure data, with the flexibility allowed only about the phosphodiester bonds. However, the crystal structure of deoxyguanosine-5'−phosphate2,3 indicates at gt conformation about the C-4'−C-5' bond against gg in a conformationally rigid nudeotide1. Jack et al. 4 considered the flexibility of nucleotides in tRNA about the C-4'−C-5' bond, thereby introducing the concept of 'non-rigid' ribonucleotides. Conformational flexibility of the f uranose ring in DNA and RNA and their energetics using classical and quantum chemical methods have been reported5−8. We have examined the flexibility of 3'-nucleotides. alpha, the most important of the conformational parameters defining the 3'-end of a nucleotide unit9, has a value in the range 195°−270° in all the 3'-nucleotides, dinucleoside monophosphates and higher oligomers which have been surveyed. A survey of the proposed structures of polyribonudeotides10,11 also shows the values of a to be greater than 200°. However, the structures proposed for B-DNA by Arnott and Hukins12,13 and D-DNA by Arnott et al. 14 have values of alpha of 155° and 141° respectively, much lower than the lowest observed value. The structure for B-DNA has two strong, short contacts (C-2'...OP-1 = 2.64 Å and HC-2"...OP-1 = 1.79 Å) which lead to an energetically unfavourable conformation. Hence, it is of interest to investigate whether, by allowing flexibility to the sugar moiety in the nucleotide unit, it is possible to make the structure energetically favourable. Here, conformational energy calculations were carried out to determine the range of alpha which would give rise to energetically favoured conformations with different sugar puckerings. Our analysis has shown that the theoretically obtained range is nearly the same as the preferred range in crystals, indicating the flexibility of the 3'-nucleotides.

Multiple liquid-crystals and NMR

The use of more than one liquid crystal solvents to determine molecular structure and conformation is discussed. Liquid crystals of similar and opposite signs of diamagnetic anisotropies are considered separately since they lead to different novel applications. Advantages of such experiments over those employing single solvents are pointed out with illustrative examples.

Theoretical studies on penicillins, penicillin sulphones and their 1-oxa-1-dethia and 1-carba-1-dethia analogues: binding specificities of transeptidases and penicillinases

Empirical potential energy calculations have been carried out to determine the preferred conformations of penicillins and penicillin sulphones and their 1-oxa-1-dethia and 1-carba-1-dethia analogues. With the exception of 1-oxa-1-dethia penicillins, all the other compounds favour C2 and the C3 puckered conformations of their five-membered rings. Replacement of C2 methyl groups by hydrogen atoms as in bisnorpenicillin V or oxidation of sulphur in position 1 as in sulphones, makes the C3 puckered form much less favourable. Addition of an amino-acyl group at the C6 atom, however, makes the C3 puckered form more favoured in penicillin G or V and in 1-carba-1-dethia penicillins. Through the replacement of the sulphur atom at position 1 by an oxygen atom or by a -CH2 group increases the non-planarity of the lactam peptide bond, it significantly affects the relative disposition of the C3 carboxyl group with respect to the β-lactam ring. These conformational differences have been correlated with the biological activities of these compounds. The present study suggests that the conformation of the bicyclic ring system may be more important for initial binding with the crosslinking enzyme(s) involved in the biosynthesis of bacterial cell-wall peptidoglycan and that the mode of binding is influenced by the nature of the side-group at the C6 atom. These studies predict, in agreement with experimental results, that the 1-oxa-1-dethia penicillin nulceus is an inhibitor of penicillianses. The study also suggests that the stereospecificities of the crosslinking enzyme(s) and penicillinases are very similar with regard to the nature of the side-group at the 6 atom and the confirmation of the bicyclic ring system. However, the confirmational requirement for the bicyclic ring system appears to be more specific in the former enzyme than in the latter.