Antonio L. Llamas-Saiz

Functional implications of the structure of the murine parvovirus, minute virus of mice

BACKGROUND Minute virus of mice (MVM) is a single-stranded (ss) DNA-containing, murine parvovirus with a capsid built up of 60 icosahedrally related polypeptide chains, each of which consists of the C-terminal region common to two structural proteins, VP1 and VP2. In infectious virions, most VP2 molecules are cleaved to VP3 by the removal of about 20 amino acids from the N terminus. Of the 587 amino acids in VP2, approximately half are identical to those in the analogous capsid protein of the antigenically distinct canine parvovirus (CPV), the crystal structure of which has previously been determined. The three-dimensional structure determination of MVMi (the immunosuppressive strain of MVM) was previously reported to 3.5 A resolution. RESULTS We report here an analysis of the MVMi virus structure and provide insights into tissue tropism, antigenicity and DNA packaging. Amino acids determining MVM tissue tropism were found to cluster on, or near, the viral surface. A conserved, glycine-rich, N-terminal peptide was seen to run through a cylindrical channel along each fivefold axis and may have implications for antigenicity. Density within the virion was interpreted as 29 ssDNA nucleotides per icosahedral asymmetric unit, and accounts for over one-third of the viral genome. CONCLUSIONS The presence of the glycine-rich sequence in the fivefold channels of MVMi provides a possible mechanism to explain how the unique N-terminal region of VP1 becomes externalized in infectious parvovirions. Residues that determine tropism may form an attachment recognition site for a secondary host-cell factor that modulates tissue specificity. The ordering of nucleotides in a similar region of the interior surface in the CPV and MVMi capsids suggests the existence of a genomic DNA-recognition site within the parvoviral capsid.

The geometry of pyrazole: A test for ab initio calculations

Ab initio calculations on the structure of pyrazole have been carried out at different levels of accuracy. At the Hartree‐Fock (HF) level, the performance of several basis sets, namely 3‐21G, 6‐31G, 6‐31G**, and 6–311G** was investigated. The influence of electron correlation effects also was studied by carrying out geometry optimizations at the MP2, MP4, and QCISD levels. The performance of a density functional method also was evaluated. We have also investigated the possible influence of the frozen core approximation on the final optimized geometry. Three different statistical analyses were considered in determining which geometry is closest to the experimental microwave geometry—namely Paul Curtins diagrams, cluster analysis, and multidimensional scaling. From these analyses, we conclude that there is no asymptotic approach to the experimental geometry by increasing the quality of the theoretical model, although, as expected, the more reliable structures are those obtained at the MP2, MP4, and QCISD levels, as well as those obtained by the B3LYP density functional method. We have also found that the values of the rotational constants are a tight criterion to define the quality of a molecular geometry.

SYNTHESIS AND MOLECULAR STRUCTURE OF 3-(2-BENZYLOXY-6-HYDROXYPHENYL)-5-STYRYLPYRAZOLES. REACTION OF 2-STYRYLCHROMONES AND HYDRAZINE HYDRATE

Abstract 3-(2-Benzyloxy-6-hydroxyphenyl)-5-styrylpyrazoles 7a-e were prepared from the reaction of 2-styrylchromones and hydrazine hydrate. 3-(2-Benzyloxy-6-hydroxyphenyl)-5-(2-phenylethyl)-pyrazoles 8a,d,e and 3-(2-benzyloxy-β,6-dihydroxystyryl)-5-aryl-2-pyrazolines 9a-e were also obtained as by-products. The crystal and molecular structure of two 3-(2-benzyloxy-6-hydroxyphenyl)-5-styrylpyrazoles 7a,b have been determined by X-Ray analysis. Although the substitution of an hydrogen by a methyl group on the double bond of the styryl moiety seems to be a minor perturbation, it produces drastic changes in the crystal packing where only one conformer is present. The OH group is involved as donor of an intramolecular hydrogen bond and the NH group is responsible for the formation of chains via intermolecular hydrogen bonds.

The influence of the substituent at the nitrogen atom on the molecular structure of pyrazoles: a crystallographic statistical survey versus ab initio calculations

Abstract A survey of the crystal structures of pyrazoles reported in the Cambridge Structural Database has been analyzed using the diagrams of Dieterich. (D.A. Dieterich, I.C. Paul and D.Y. Curtin, J. Am. Chem. Soc., 96 (1974) 6372). Structures have been classified according to the substituent at position 1 of the pyrazole ring. A total of 209 data were analyzed. For eight representative N -substituents (H, CH 3 , CHO, NH 2 , NO 2 , PH 2 , BH 2 and BH − 3 ) ab initio calculations at the 6-31G** level have been carried out. The average geometries for these groups of pyrazoles and those calculated theoretically are generally in good agreement considering the assumed simplifications (not taking into account the effect of the C-substituents, reduction of the N-substituent to its simpler expression). The effect of substituents on nitrogen parallels that on carbon in benzene rings with the exception of the amino group.

Ab initio study of the effect of N-substituents on properties of pyrazoles

Abstract A series of fourteen derivatives of pyrazole have been calculated at the MP2-6-31G ∗∗ level. The first thirteen are derivatives of the parent pyrazole with different substituents on the nitrogen N(1) and the last one is pyrazole N -oxide. The substituents have been selected to cover a wide range of electronic effects. The theoretical results are discussed in relation with geometries, energies, vibrational spectra, Bader analysis and tautomerism (in the case 1-hydroxypyrazole/pyrazole N -oxide).

SYNTHESIS AND MOLECULAR STRUCTURE OF NEW O/N/O LIGANDS : BIS-PHENOL-PYRIDINE AND BIS-PHENOL-PYRAZOLE

Abstract Two new heterocyclic ligands, 2,6-bis-(2′-hydroxyphenyl)pyridine 2 and 3,5-bis-(2′-hydroxyphenyl)pyrazole 4 have been prepared. The molecular structures of 2,6-bis-(2′-methoxyphenyl)pyridine 1, the tetrafluoroborate salt of 2,6-bis-(2′-hydroxyphenyl)pyridine 3 (a monohydrate) and that of compound 4 have been determined by X-Ray analysis. In 1, the phenyl rings are oriented so that the oxygen atoms of the methoxy groups are placed away from the nitrogen of the pyridine to overcome electronic repulsion. In salt 3, intramolecular hydrogen bonds are found between the pyridinium proton and the hydroxyl atoms which are involved in strong OH…O and OH…F interactions. In addition, the water molecule participates in a bridging hydrogen bond network with the BF4−. The molecules in 4, are also held together by hydrogen bonds where the hydroxyl groups act as both a donor and an acceptor and are responsible for the formation of chains.

Structure of 3(5)-methyl-4-nitropyrazole in the solid state: tautomerism, crystallography and the problem of desmotropy

The first example of desmotropy in azoles has been found concerning 3-methyl-4-nitropyrazole and its tautomer, 5-methyl-4-nitropyrazole: the crystal and molecular stucture of both tautomers has been determined by X-ray analysis, 13C CPMAS NMR spectroscopy has been used for studying the isomerization processes in the solid state.

The search for proton mobility in solid pyrazoles: molecular and crystal structure of 3(5)-phenyl-4-bromo-5(3)-methylpyrazole

Abstract The crystal structure of 3(5)-phenyl-4-bromo-5(3)-methylpyrazole, 3, has been determined by X-ray crystallography. Both tautomers are present simultaneously in the crystals forming cyclic tetramers. The proton disorder, determined by the crystallographic methods, has been established to be dynamic using solid state 13C CPMAS NMR spectroscopy. This is a new example of an asymmetrically 3,5-disubstituted pyrazole that presents solid state intermolecular proton transfer. The arrangement of the tautomers in the cyclic tetramer is different to the case of 3(5)-phenyl-5(3)-methylpyrazole, 2, previously described.

STRUCTURE OF 3-NITROPYRAZOLE IN SOLUTION AND IN THE SOLID STATE

The molecular and crystal structure of 3-nitropyrazole was determined by X-ray analysis. The triclinic unit cell contains 12 molecules which form four hydrogen-bonded (N—H···N) trimers. Each trimer comprises of pseudo-ring in a flattened envelope distorted towards a chair conformation. The crystal packing consists of layers formed by centrosymmetric related trimers joined through C‐H···O interactions. Ab initio calculations were performed on 3(5)-nitro- and 4-nitropyrazole and their corresponding protonated forms up to the MP2/6‐31G** level of theory. The origin of the difference in aqueous basicities between both nitropyrazoles is discussed.

A comparison of the structures of pyrazole, 3,5-dimethylpyrazole and 3,5-bis(trifluoromethyl)pyrazole: theoretical calculations (STO-3G), microwave, electron diffraction and crystallography

Abstract The first two examples of pyrazole structures determined by electron diffraction are reported. These geometries and that of pyrazole itself (known from a microwave study) are discussed in comparison with STO-3G ab initio calculations and with X-ray geometries. Theoretically optimized geometries agree with the experimental ones, both describing consistently the electronic effects and conformation of methyl and trifluoromethyl substituents with regard to the solid state geometries, it appears that 3,5-dimethylpyrazole has a classical C s structure in the gas phase consistent with the averaged C 2v structure of the crystal (dynamically disordered).