Molecular structure of Lantadene-B&C, triterpenoids ofantana camara, red variety: Lantadene-B, 22β-angeloyloxy-3-oxoolean-12-en-28-oic acid; Lantadene-C, 22 β-(S)-2′-methyl butanoyloxy-3-oxoolean-12-en-28-oic acid

(I)Lantadene-B: C35H52O5,M r =552.80, MonoclinicC2,a=25.65(1),b=6.819(9),c=18.75(1) Å,beta=100.61(9),V=3223(5) Å3,Z=4,D x =1.14 g cm–3 CuKagr (lambda=1.5418A),mgr=5.5 cm–1,F(000)=1208,R=0.118,wR=0.132 for 1527 observed reflections withF o ge2sgr(F o ). (II)Lantadene-C: C35H54O5·CH3OH,Mr=586.85, Monoclinic,P21,a=9.822(3),b=10.909(3),c=16.120(8)Å,beta=99.82(4),V=1702(1)Å3,Z=2,D x =1.145 g cm–3, MoKagr (lambda=0.7107Å), mgr=0.708 cm–1 F(000)=644,R=0.098, wR=0.094 for 1073 observed reflections. The rings A, B, C, D, and E aretrans, trans, trans, cis fused and are in chair, chair, sofa, half-chair, chair conformations, respectively, in both the structures. In the unit cell the molecules are stabilized by O-HctdotO hydrogen bonds in both the structures, however an additional C-HctdotO interaction is observed in the case of Lantadene-C.

Molecular theory of ion solvation dynamics in water, acetonitrile and methanol: A unified microscopic description of collective dynamics in dipolar liquids

A recently developed microscopic theory of solvation dynamics in real dipolar liquids is used to calculate, for the first time, the solvation time correlation function in liquid acetonitrile, water and methanol. The calculated results are in excellent agreement with known experimental and computer simulation studies.

Molecular theory of underdamped dielectric relaxation: understanding collective effects in dipolar liquids

A molecular theory of underdamped dielectric relaxation of a dense dipolar liquid is presented. This theory properly takes into account the collective effects that are present (due to strong intermolecular correlations) in a dipolar liquid. For small rigid molecules, the theory again leads to a three-variable description which, however, is somewhat different from the traditional version. In particular, two of the three parameters are collective in nature and are determined by the orientational pair correlation function. A detailed comparison between the theory and the computer simulation results of Neria and Nitzan is performed and an excellent agreement is obtained without the use of any adjustable or free parameter - the calculation is fully microscopic. The theory can also provide a systematic description of the Poley absorption often observed in dipolar liquids in the high-frequency regime.

NDDO-based CI methods for the prediction of electronic spectra and sum-over-states molecular hyperpolarization

NDDO-based (AM1) configuration interaction (CI) calculations have been used to calculate the wavelength and oscillator strengths of electronic absorptions in organic molecules and the results used in a sum-over-states treatment to calculate second-order-hyperpolarizabilities. The results for both spectra and hyperpolarizabilities are of acceptable quality as long as a suitable CI-expansion is used. We have found that using an active space of eight electrons in eight orbitals and including all single and pair-double excitations in the CI leads to results that agree well with experiment and that do not change significantly with increasing active space for most organic molecules. Calculated second-order hyperpolarizabilities using this type of CI within a sum-over-states calculation appear to be of useful accuracy.

Proton NMR study of molecular dynamics in ammonium tribromo stannate (NH4SnBr3)

The proton second moment M2 and spin-lattice relaxation time T1 have been measured in ammonium tribromo stannate (NH4SnBr3) in the temperature range 77–300 K, to determine the ammonium dynamics. The continuous wave signal is strong and narrow at 77 and 300 K but has revealed an interesting intensity anomaly between 210 and 125 K. T1 shows a maximum (13 s) around 220 K. No minimum in the T1 vs 1000/T plot was observed down to 77 K. M2 and T1 results are interpreted in terms of NH+4 ion dynamics. The activation energy Ea for NH+4 ion reorientation is estimated to be 1.4 kcal mol−1.

Pulsed NMR study of molecular motions and phase transitions in [N(CH3)4]PbX3 (X=Cl, Br, I)

Proton spin—lattice relaxation time (T1) is measured in [N(CH3)4]PbX3 (X=Cl, Br, I) from 300-77 K at 9.75 MHz. All the compounds show discontinuous changes in T1 values (at 256, 270 and 277 K, respectively), indicating phase transitions. Single T1 minimum is observed in all the cases and the T1 variation is explained in terms of [N(CH3)4] and CH3 group dynamics. The activation energy Eα decreases from chloride to iodide (from 4 to 2 kcal/mol). In bromide and iodide, T1 is found to decrease with increase in temperature at higher temperatures, indicating the presence of spin—rotation interaction.

Biocompatibility and biofunctionalization of mesoporous silicon particles

Several of the newly developed drug molecules experience poor biopharmaceutical behavior, which hinders their effective delivery at the proper site of action. Among the several strategies employed in order to overcome this obstacle, mesoporous silicon-based materials have emerged as promising drug carriers due to their ability to improve the dissolution behavior of several poorly water-soluble drugs compounds confined within their pores. In addition to improve the dissolution behavior of the drugs, we report that porous silicon (PSi) nanoparticles have a higher degree of biocompatibility than PSi microparticles in several cell lines studied. In addition, the degradation of the nanoparticles showed its potential to fast clearance in the body. After oral delivery, the PSi particles were also found to transit the intestines without being absorbed. These results constituted the first quantitative analysis of the behavior of orally administered PSi nanoparticles compared with other delivery routes in rats. The self-assemble of a hydrophobin class II (HFBII) protein at the surface of hydrophobic PSi particles endowed the particles with greater biocompatibility in different cell lines, was found to reverse their hydrophobicity and also protected a drug loaded within its pores against premature release at low pH while enabling subsequent drug release as the pH increased. These results highlight the potential of HFBII-coating for PSi-based drug carriers in improving their hydrophilicity, biocompatibility and pH responsiveness in drug delivery applications. In conclusion, mesoporous silicon particles have been shown to be a versatile platform for improving the dissolution behavior of poorly water-soluble drugs with high biocompatibility and easy surface modification. The results of this study also provide information regarding the biofunctionalization of the THCPSi particles with a fungal protein, leading to an improvement in their biocompatibility and endowing them with pH responsive and mucoadhesive properties.

Role of molecular reorientation in the vitrification of molecular liquids: A Monte Carlo study of the liquid and glassy states of 2,2-dimethylbutane

The liquid and the glassy phases of 2,2-dimethylbutane have been investigated by isothermal isobaric ensemble Monte Carlo simulation. Thermodynamic Properties and radial distribution functions for both the liquid and the glass have been obtained. The radial distribution functions have been classified into three types based on the accessibility of the group. It has been shown that the structure of the Iiquid and the glass can be understood in terms of the above classification of the radial distribution functions. Molecular reorientation plays an important role in the structural rearrangement accompanying glass formation. As much as 35% of the contribution to the increase in the intermolecular interaction energy on vitrification is due to the reorientation of the neighbouring pairs of molecules. The observed changes in the dimerisation energy and the bonding energy distribution function are consistent with the observed structural changes.

Solvation dynamics in a Brownian dipolar lattice. Comparison between computer simulation and various molecular theories of solvation dynamics

Several recent theoretical and computer simulation studies have considered solvation dynamics in a Brownian dipolar lattice which provides a simple model solvent for which detailed calculations can be carried out. In this article a fully microscopic calculation of the solvation dynamics of an ion in a Brownian dipolar lattice is presented. The calculation is based on the non‐Markovian molecular hydrodynamic theory developed recently. The main assumption of the present calculation is that the two‐particle orientational correlation functions of the solid can be replaced by those of the liquid state. It is shown that such a calculation provides an excellent agreement with the computer simulation results. More importantly, the present calculations clearly demonstrate that the frequency‐dependent dielectric friction plays an important role in the long time decay of the solvation time correlation function. We also find that the present calculation provides somewhat better agreement than either the dynamic mean spherical approximation (DMSA) or the Fried–Mukamel theory which use the simulated frequency‐dependent dielectric function. It is found that the dissipative kernels used in the molecular hydrodynamic approach and in the Fried–Mukamel theory are vastly different, especially at short times. However, in spite of this disagreement, the two theories still lead to comparable results in good agreement with computer simulation, which suggests that even a semiquantitatively accurate dissipative kernel may be sufficient to obtain a reliable solvation time correlation function. A new wave vector and frequency‐dependent dissipative kernel (or memory function) is proposed which correctly goes over to the appropriate expressions in both the single particle and the collective limits. This form is expected to lead to better results than all the existing descriptions.

Sorbate properties and cage-to-cage diffusion of argon in NaCaA: a molecular dynamics study

Detailed molecular dynamics simulations of argon in zeolite NaCaA are reported. Thermodynamic, structural, and dynamical properties of the sorbate as a function of temperature have been obtained. The properties calculated include various site-site radial distribution functions, different energy distribution functions, selfdiffusion coefficients, the power spectra, and properties relating to cage-to-cage diffusion. The results suggest that sorbate is delocalized above 300 K. Both modes of cage-to-cage diffusion-the surface-mediated and centralized diffusion-are associated with negative barrier heights. Surprisingly, rate of cage-to-cage diffusion is associated with negative and positive activation energies below and above 500 K. The observed differences in the behavior of the rate of cage-to-cage diffusion between Xe-NaY and Ar-NaCaA systems and the nature of the potential energy surface are discussed. Presence of sorbatezeolite interactions results in significant enhancement in the rate of cage-to-cage diffusion and rate of cage visits. It is shown that properties dependent on the long-time behavior such as the diffusion coefficient and the rate of cages visited exhibit the expected Arrhenius dependence on temperature.

Stereochemistry of 2'-5' linked nucleic acids: crystal and molecular structure of ammonium adenylyl-2',5'-adenosine tetrahydrate: a core fragment of 2'-5' oligo A's produced by interferon induced adenylate synthetase

The preponderance of 3'-5' phosphodiester links in nucleic acids is well known. Albeit less prevalent, the 2'-5' links are specifically utilised in the formation of 'lariat' in group II introns and in the msDNA-RNA junction in myxobacterium. As a sequel to our earlier study on cytidylyl-2',5'-adenosine we have now obtained the crystal structure of adenylyl-2',5'-adenosine (A2'p5'A) at atomic resolution. This dinucleoside monophosphate crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 7.956(3) A, b = 12.212(3) A and c = 36.654(3) A. CuK alpha intensity data were collected on a diffractometer. The structure was sloved by direct methods and refined by full matrix least squares methods to R = 10.8%. The 2' terminal adenine is in the commonly observed anti (chi 2 = 161 degrees) conformation and the 5' terminal base has a syn (chi 1 = 55 degrees) conformation more often seen in purine nucleotides. A noteworthy feature of A2'p5'A is the intranucleotide hydrogen bond between N3 and O5' atoms of the 5' adenine base. The two furanose rings in A2'p5'A show different conformations - C2' endo, C3' endo puckering for the 5' and 2' ends respectively. In this structure too there is a stacking of the purine base on the ribose O4' just as in other 2'-5' dinucleoside structures, a feature characteristically seen in the left handed Z DNA. In having syn, anti conformation about the glycosyl bonds, C2' endo, C3' endo mixed sugar puckering and N3-O5' intramolecular hydrogen bond A2'p5'A resembles its 3'-5' analogue and several other 2'-5' dinucleoside monophosphate structures solved so far. Striking similarities between the 2'-5' dinucleoside monophosphate structures suggest that the conformation of the 5'-end nucleoside dictates the conformation of the 2' end nucleoside. Also, the 2'-5' dimers do not favour formation of miniature classical double helical structures like the 3'-5' dimers. It is conceivable, 2-5(A) could be using the stereochemical features of A2'p5'A which accounts for its higher activity.

Molecular diagnosis of developmental disorders

ABSTRACT Idiopathic developmental disorders (DDs) affect ~1% of the population worldwide. This being a considerable amount, efforts are being made to elucidate the disease mechanisms. One or several genetic factors cause 30-40% of DDs, and only 10% are caused by environmental factors. The remaining 50% of DD patients go undiagnosed, mostly due to a lack of diagnostic techniques. The cause in most undiagnosed cases is though to be a genetic factor or a combination of genetic and environmental factors. Despite the surge of new technologies entering the market, their implementation into diagnostic laboratories is hampered by costs, lack of information about the expected diagnostic yield, and the wide range of selection. This study evaluates new microarray methods in diagnosing idiopathic DDs, providing information about their added diagnostic value. Study I analysed 150 patients by array comparative genomic hybridization (array CGH, 44K and 244K), with a subsequent 18% diagnostic yield. These results are supported by other studies, indicating an enourmous added diagnostic value of array CGH, compared with conventional cytogenetic analysis. Nevertheless, 80% of the patients remained undiagnosed in Study I. In an effort to diagnose more patients, in Study IV the resolution was increased from 8.9 Kb of the 244K CGH array to 0.7 Kb, by using a single-nucleotide polymorphism (SNP) array. However, no additional pathogenic changes were detected in the 35 patients assessed, and thus, for diagnostic purposes, an array platform with ca 9 Kb resolution appears adequate. The recent vast increase in reports of detected aberrations and associated phenotypes has enabled characterization of several new syndromes first based on a common aberration and thereafter by delineation of common clinical characteristics. In Study II, a familial deletion at 9q22.2q22.32 with variable penetrance was described. Despite several reports of aberrations in the adjacent area at 9q associated with Gorlin syndrome, the patients in this family had a unique phenotype and did not present with the syndrome. In Study III, a familial duplication of chromosome 6p22.2 was described. The duplication caused increased expression of an important enzyme of the γ-aminobutyric acid (GABA) degradation pathway, causing oxidative stress of the brain, and thus, very likely, the mild mental retardation of these patients. These two case studies attempted to pinpoint candidate genes and to resolve the pathogenic mechanism causing the clinical characteristics of the patients. Presenting rare genetic and clinical findings to the international science and medical community enables interpretation of similar findings in other patients. The added value of molecular karyotyping in patients with idiopathic DD is evident. As a first line of testing, arrays with a median resolution of at least 9 Kb should be considered and further characterization of detected aberrations undertaken when possible. Diagnostic whole-exome sequencing may be the best option for patients who remain undiagnosed after high-resolution array analysis.

Amorphous Mesoporous Iron Aluminophosphate Catalyst for the Synthesis of 1,5-Benzodiazepines

A simple and versatile method for the synthesis of 1,5-benzodiazepines from o-phenylenediamine and ketones in the presence of solvents and under solvent-free conditions that used an amorphous mesoporous iron aluminophosphate as catalyst was developed. High yields with excellent selectivity were obtained with a wide variety of ketones under mild reaction conditions. The catalyst had the advantages of ease of preparation, ease of handling, simple recovery, reusability, non toxicity, and being inexpensive.

Ab initio molecular orbital calculations on ion pair-water complexes of metal halides and oxides

Ab initio MO calculations are performed on a series of ion-molecular and ion pair-molecular complexes of H2O + MX (MX = LiF, LiCl, NaCl, BeO and MgO) systems. BSSE-corrected stabilization energies, optimized geometrical parameters, internal force constants and harmonic vibrational frequencies have been evaluated for all the structures of interest. The trends observed in the geometrical parameters and other properties calculated for the mono-hydrated contact ion pair complexes parallel those computed for the complexes of the individual ions. The bifurcated structures are found to be saddle points with an imaginary frequency corresponding to the rocking mode of water molecules. The solvent-shared ion pair complexes have high interaction energies. Trends in the internal force constant and harmonic frequency values are discussed in terms of ion-molecular and ion-pair molecular interactions.

A Molecular Dynamics Study of Atomic Correlations in Glassy BzS3t

Glassy B&, the parent compound of the superionic conductor LiI-Li&B& has been studied by the molecular dynamics technique using a new potential model. The results suggest that the glass is made up of local units of four-membered B2S2 rings bridged by sulfur atoms, leading to a chainlike structure. Various pair correlation functions have been analyzed, and the B2Sz rings have been found to be planar. The calculated neutron structure factor shows a peak at 1.4 A-' which has been attributed to B-B correlations at 5.6 A. The glass transition temperature of the simulated system has been calculated to be around 800 K.