Charge density based classification of intermolecular interactions in molecular crystals

Evaluation of intermolecular interactions in terms of both experimental and theoretical charge density analyses has produced a unified picture with which to classify strong and weak hydrogen bonds, along with van der Waals interactions, into three regions.

A combined extended and helical backbone for Boc-(Ala-Leu-Ac(7)c-)(2)-OMe

The structure of the peptide Boc-Ala-Leu-Ac(7)c-Ala-Leu-Ac(7)c-OMe (Ac(7)c,1-aminocycloheptane-1-carboxylic acid) is described in crystals. The presence of two Ac(7)c residues was expected to stabilize a 3(10)-helical fold. Contrary to expectation the structural analysis revealed an unfolded amino terminus, with Ala(1) adopting an extended beta-conformation (phi = -93degrees,psi = 112degrees). Residues 2-5 form a 3(10)-helix, stabilized by three successive intramolecular hydrogen bonds. Notably, two NH groups Ala(1) and Ac(7)c(3) do not form any hydrogen bonds in the crystal. Peptide assembly appears to be dominated by packing of the cycloheptane rings that stack against one another within the molecule and also throughout the crystal in columns.

Hybrid peptide hairpins containing alpha- and omega-amino acids: Conformational analysis of decapeptides with unsubstituted beta-, gamma-, and delta-residues at positions 3 and 8

The effects of inserting unsubstituted omega-amino acids into the strand segments of model beta-hairpin peptides was investigated by using four synthetic decapeptides, Boc-Lcu-Val-Xxx-Val-D-Pro-Gly-Leu-Xxx-Val-Val- OMe: pepticle 1 (Xxx=Gly), pepticle 2 (Xxx=beta Gly=beta hGly=homoglycine, beta-glycine), pepticle 3 (Xxx=gamma Abu=gamma-aminobutyric acid), pepticle 4 (Xxx= delta Ava=delta-aminovaleric acid). H-1 NMR studies (500 MHz, methanol) reveal several critical cross-strand NOEs, providing evidence for P-hairpin conformations in peptides 2-4. In peptide 3, the NMR results support the formation of the nucleating turn, however, evidence for cross-strand registry is not detected. Single-crystal X-ray diffraction studies of peptide 3 reveal a beta-hairpin conformation for both molecules in the crystallographic asymmetric unit, stabilized by four cross-strand hydrogen bonds, with the gamma Abu residues accommodated within the strands. The D-Pro-Gly segment in both molecules (A,B) adopts a type II' beta-turn conformation. The circular dichroism spectrum for peptide 3 is characterized by a negative CD band at 229 rim, whereas for peptides 2 and 4, the negative band is centered at 225 nm, suggesting a correlation between the orientation of the amide units in the strand segments and the observed CD pattern.

Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I 'beta-turn forming tetrapeptide and an alpha-helical tetradecapeptide

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I' beta-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt alpha-helical conformations stabilized by 11 successive 5 -> 1 hydrogen bonds. In addition, a single 4 -> 1 hydrogen bond is also observed at the N-terminus. All live Dpg residues adopt backbone torsion angles (phi, psi) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-C-alpha-C' (tau) and the observed backbone phi,psi values. For tau > 106 degrees, helices are observed, while fully extended structures are characterized by tau < 106 degrees. The mean r values for extended and folded conformations for the Dpg residue are 103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Multiple conformational states in crystals and in solution in alpha gamma hybrid peptides. Fragility of the C-12 helix in short sequences

The conformational properties of foldamers generated from alpha gamma hybrid peptide sequences have been probed in the model sequence Boc-Aib-Gpn-Aib-Gpn-NHMe. The choice of alpha-aminoisobutyryl (Aib) and gabapentin (Gpn) residues greatly restricts sterically accessible coil formational space. This model sequence was anticipated to be a short segment of the alpha gamma C-12 helix, stabilized by three successive 4 -> 1 hydrogen bonds, corresponding to a backbone-expanded analogue of the alpha polypeptide 3(10)-helix. Unexpectedly, three distinct crystalline polymorphs were characterized in the solid state by X-ray diffraction. In one form, two successive C-12 hydrogen bonds were obtained at the N-terminus, while a novel C-17 hydrogen-bonded gamma alpha gamma turn was observed at the C-terminus. In the other two polymorphs, isolated C-9 and C-7 hydrogen-bonded turns were observed at Gpn (2) and Gpn (4). Isolated C-12 and C-9 turns were also crystallographically established in the peptides Boc-Aib-Gpn-Aib-OMe and Boc-Gpn-Aib-NHMe, respectively. Selective line broadening of NH resonances and the observation of medium range NH(i)<-> NH(i+2) NOEs established the presence of conformational heterogeneity for the tetrapeptide in CDCl3 solution. The NMR results are consistent with the limited population of the continuous C-12 helix conformation. Lengthening of the (alpha gamma)(n) sequences in the nonapeptides Boc-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Xxx (Xxx = Aib, Leu) resulted in the observation of all of the sequential NOEs characteristic of an alpha gamma C-12 helix. These results establish that conformational fragility is manifested in short hybrid alpha gamma sequences despite the choice of conformationally constrained residues, while stable helices are formed on chain extension.

Solution structures of conformationally equilibrium forms of holo-acyl carrier protein (PfACP) from Plasmodium falciparum provides insight into the mechanism of activation of ACPs

Acyl Carrier Protein (ACP) from the malaria parasite, Plasmodium falciparum (PfACP) in its holo form is found to exist in two conformational states in solution. Unique 3D solution structures of holo-PfACP have been determined for both equilibrium conformations, using high-resolution NMR methods. Twenty high-resolution solution structures for each of the two forms of holo-PfACP have been determined on the basis of 1226 and 1218 unambiguously assigned NOEs (including NOEs between 4 '-phosphopantetheine prosthetic group (4 '-PP) and protein), 55 backbone dihedral angles and 26 hydrogen bonds. The atomic rmsd values of the determined structures of two equilibrium forms, about the mean coordinates of the backbone and heavy atoms, are 0.48 +/- 0.09 and 0.92 +/- 0.10 and 0.49 +/- 0.08 and 0.97 +/- 0.11 angstrom, respectively. The interaction of 4 '-PP with the polypeptide backbone is reported here for the first time for any of the ACPs. The structures of holo-PfACP consist of three well-defined helices that are tightly packed. The structured regions of the molecule are stabilized by extensive hydrophobic interactions. The difference between the two forms arises from a reorientation of the 4 '-PP group. The enthalpy difference between the two forms, although small, implies that a conformational switch is essential for the activation of holo-ACP. Sequence and structures of holo-PfACP have been compared with those of the ACPs from type I and type II fatty acid biosynthesis pathways (FAS), in particular with the ACP from rat and the butyryl-ACP from E. coli. The PfACP structure, thus determined has several novel features hitherto not seen in other ACPs.

Charge distribution, dipole moments and infrared spectra of some thiol and thio acids

The dipole moments of thioglycollic (2.28 D), β-mereaptopropionic (2.25 D), thiomalic (2.47 D), malic (3.12 D), and dithiodiacetic (3.17 D) acids have been measured in dioxan at 35° C. Using the scheme of Smith, Ree, Magee and Eyring, the formal charge distribution in and hence the electric moments of these acids have been evaluated, compared with the theoretical moments, and discussed in terms of their various possible structures. Infrared spectra of these acids (liquid and nujol mull) indicate association through hydrogen bonding. These bonds are broken in solution. © 1969.

Charge distribution, dipole moments and infrared spectra of some thiol and thio acids

The dipole moments of thioglycollic (2.28 D), β-mereaptopropionic (2.25 D), thiomalic (2.47 D), malic (3.12 D), and dithiodiacetic (3.17 D) acids have been measured in dioxan at 35° C. Using the scheme of Smith, Ree, Magee and Eyring, the formal charge distribution in and hence the electric moments of these acids have been evaluated, compared with the theoretical moments, and discussed in terms of their various possible structures. Infrared spectra of these acids (liquid and nujol mull) indicate association through hydrogen bonding. These bonds are broken in solution.

Physicochemical studies on the gelation of hen egg yolk; separation of gelling protein components from yolk plasma

A study of the component(s) in egg yolk responsible for gelation of yolk on freezing and thawing has shown that granule-free yolk plasma, obtained by high-speed centrifugation of yolk, has the capacity to gel. As with the whole yolk, gelation of yolk plasma on freezing and thawing could be inhibited by additives such as sugars, sodium chloride, proteolytic enzymes, and phospholipase-A. Phospholipase-C, which induces gelation of whole yolk at room temperature, has a similar effect on yolk plasma. Yolk plasma has been separated into aggregating (gelling) and soluble fractions by delipidation, using formic acid. Each of these fractions consists of three or four protein components, as observed by gel filtration, ultracentrifugation, and agar electrophoresis. The proteins are glycoproteins and contain bound hexoses, hexosamine, and sialic acid. The gelation of yolk has been attributed to the interactions between protein molecules following disruption of lipid-protein bonds.

Infrared absorption spectra of single crystals of glycine silver nitrate and monoglycine nitrate

he infrared absorption spectra of glycine silver nitrate (GAgNO3) and glycine nitrate (GHNO3) show that the glycine group exists completely in the zwitter ion form in the former and in both forms in the latter. The spectrum of GAgNO3 at liquid air temperature did not reveal any striking change which can be attributed to a freezing of the rapid reorientation of the NH3+ group taking place at higher temperatures. The position of the COO− stretching frequencies indicate that this group is co-ordinated only weakly to the Ag+ ion. The summation frequencies reported by Schroeder, Wier and Lippincott (1962) for AgNO3 were not observed in the present study on GAgNO3. It shows however that ferroelectricity in GAgNO3 is in all probability due to the motion of the Ag+ ion in the oxygen co-ordination polyhedron and is not directly connected with the ordering of the hydrogen bonds below Curie point.

Infra-red and raman spectra of BaCl2.2H2O and BaCl2.2D2O

The infra-red and Raman spectra of ordinary and deuterated barium chloride dihydrate have been studied to throw light on the intramolecular hydrogen bonds in these two crystals. The frequencies of the stretching, bending and librational modes observed in infra-red and Raman spectra exclude the possibility of at least one of the OH.... Cl hydrogen bonds, contrary to the results of NMR and neutron diffraction studies.

Raman spectrum of guanidinium aluminium sulphate hexahydrate

The Raman spectrum of guanidinium aluminium sulphate hexahydrate also known as ‘GASH’ which is a ferro-electric crystal and has strong hydrogen bonds has been recorded. 38 Raman lines have been identified in the spectra of GASH. The O-H stretching mode is found to be very much influenced by the hydrogen bond and they appear over a widely extended region from 2240–3600 cm.−1 It can therefore be concluded that all the O-H bonds are hydrogen bonded and some of them are quite strong. The Raman lines due to the N-H vibrations appear with the normal frequency shifts indicating thereby that N-H bonds are not hydrogen bonded. These conclusions are fully supported by the results obtained from the X-ray crystal structure analysis of GASH. The principal vibrations of the Al-(OH2)6 groups have also been identified.

Influence of the hydrogen bond on the N-H stretching frequencies in amino-acids

The spectra of glycine, its addition compounds and other amino-acids exhibit Raman lines in the region from 3250 cm.−1 to 2500 cm.−1 It has been shown that these lines cannot be assigned to N-H...O stretching vibrations, where the N atom has the covalency of three, but to N+-H...O stretching vibration where the N atom has the covalency of four. Using the data obtained with triglycine sulphate which has the largest number of N+-H...O bonds and whose H bond lengths are known, the correlation curve giving the relation between the N+-H...O stretching frequencies and the corresponding H bond lengths has been drawn. Using this correlation curve, the N+-H...O stretching frequencies appearing inα-glycine,γ-glycine, diglycine hydrochloride, diglycine hydrobromide,l-asparagine monohydrate anddl-alanine have been satisfactorily accounted for on the basis of the known hydrogen bond lengths in these substances.

Raman spectrum of hydroxylamine hydrochloride (NH3OH.Cl)

The Raman spectrum of hydroxylamine hydrochloride (NH3OH.Cl) in the form of a single crystal has been photographed usingλ 2536·5 excitation. 32 Raman lines with frequency shifts 40, 57, 78, 88, 111, 125, 135, 156, 187, 217, 250, 330, 550, 575, 1004, 1168, 1204, 1470, 1496, 1565, 1590, 1979, 2636, 2710, 2750, 2789, 2926, 2970, 3000, 3050, 3141 and 3220 cm.−1 have been recorded. Of these, the first 8 low-frequency lines belong to the external oscillation, while the four lines at 187, 217, 250 and 330 cm.−1 should be attributed to the vibrations of the hydrogen bond valence vibrations. The remaining Raman lines have been assigned to the vibrations of the NH3OH ion. The O-H and N-H stretching vibrations are very much influenced by the presence of the hydrogen bonds in the crystal.

3-(4-Chlorophenyl)-5-phenyl-1,2,4-triazolo[3,4-a]isoquinoline

In the title molecule, C22H14ClN3, the triazoloisoquinoline ring system is approximately planar, with an r.m.s. deviation of 0.033 (2) angstrom and a maximum departure from the mean plane of 0.062 (1) angstrom for the triazole ring C atom, bonded to the benzene ring. The benzene and phenyl rings are twisted by 57.02 (6) and 62.16 (6)degrees, respectively, to the mean plane of the triazoloisoquinoline ring system. The molecule is stabilized by a weak intramolecular pi-pi interaction [centroid-centroid distance = 3.7089 (10) angstrom] between the benzene and phenyl rings. In the crystal structure, weak intermolecular C-H center dot center dot center dot N hydrogen bonds and C-H center dot center dot center dot pi interactions link the molecules.