Organocatalytic Enantioselective Formal C(sp(2))-H Alkylation

An organocatalytic enantioselective formal C(sp(2))-H alkylation is reported. This alkylative desymmetrization of prochiral 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a bifunctional tertiary aminourea derivative, utilizes air-stable and inexpensive nitroalkanes as the alkylating agents, and delivers synthetically versatile five-membered carbocycles containing an all-carbon quaternary stereogenic center remote from the reaction site in excellent enantioselectivity.

IR spectroscopy as a probe for C-H center dot center dot center dot X hydrogen bonded supramolecular synthons

Weak hydrogen bonds of the type C-H center dot center dot center dot X (X: N, O, S and halogens) have evoked considerable interest over the years, especially in the context of crystal engineering. However, association patterns of weak hydrogen bonds are generally difficult to characterize, and yet the identification of such patterns is of interest, especially in high throughput work or where single crystal X-ray analysis is difficult or impossible. To obtain structural information on such assemblies, we describe here a five step IR spectroscopic method that identifies supramolecular synthons in weak hydrogen bonded dimer assemblies, bifurcated systems, and p-electron mediated synthons. The synthons studied here contain C-H groups as hydrogen bond donors. The method involves: (i) identifying simple compounds/cocrystals/salts that contain the hydrogen bonded dimer synthon of interest or linear hydrogen bonded assemblies between the same functionalities; (ii) scanning infrared (IR) spectra of the compounds; (iii) identifying characteristic spectral differences between dimer and linear; (iv) assigning identified bands as marker bands for identification of the supramolecular synthon, and finally (v) identifying synthons in compounds whose crystal structures are not known. The method has been effectively implemented for assemblies involving dimer/linear weak hydrogen bonds in nitrobenzenes (C-H center dot center dot center dot O-NO), nitro-dimethylamino compounds (NMe2 center dot center dot center dot O2N), chalcones (C-H center dot center dot center dot O=C), benzonitriles (C-H center dot center dot center dot N C) and fluorobenzoic acids (C-H center dot center dot center dot F-C). Two other special cases of C-H center dot center dot center dot pi and N-H center dot center dot center dot pi synthons were studied in which the band shape of the C-H stretch in hydrocarbons and the N-H deformation in aminobenzenes was examined.

Quorum Sensing and Biofilm Formation in Mycobacteria: Role of c-di-GMP and Methods to Study This Second Messenger

Bacteria have evolved to survive the ever-changing environment using intriguing mechanisms of quorum sensing (QS). Very often, QS facilitates formation of biofilm to help bacteria to persist longer and the formation of such biofilms is regulated by c-di-GMP. It is a well-known second messenger also found in mycobacteria. Several methods have been developed to study c-di-GMP signaling pathways in a variety of bacteria. In this review, we have attempted to highlight a connection between c-di-GMP and biofilm formation and QS in mycobacteria and several methods that have helped in better understanding of c-di-GMP signaling. (c) 2014 IUBMB Life, 66(12):823-834, 2014

Quadrature Domains in C-n

We prove two density theorems for quadrature domains in , . It is shown that quadrature domains are dense in the class of all product domains of the form , where is a smoothly bounded domain satisfying Bell's Condition R and is a smoothly bounded domain and also in the class of all smoothly bounded complete Hartogs domains in C-2.

On linear series and a conjecture of D. C. Butler

Let C be a smooth irreducible projective curve of genus g and L a line bundle of degree d generated by a linear subspace V of H-0 (L) of dimension n+1. We prove a conjecture of D. C. Butler on the semistability of the kernel of the evaluation map V circle times O-C -> L and obtain new results on the stability of this kernel. The natural context for this problem is the theory of coherent systems on curves and our techniques involve wall crossing formulae in this theory.

Rrp1B gene polymorphism (1307T > C) in metastatic progression of breast cancer

Rrp1B (ribosomal RNA processing1 homolog B) is a novel candidate metastasis modifier gene in breast cancer. Functional gene assays demonstrated that a physical and functional interaction existing between Rrp1b and metastasis modifier gene SIPA1 causes reduction in the tumor growth and metastatic potential. Ectopic expression of Rrp1B modulates various metastasis predictive extra cellular matrix (ECM) genes associated with tumor suppression. The aim of this study is to determine the functional significance of single nucleotide polymorphism (SNP) in human Rrp1B gene (1307 T > C; rs9306160) with breast cancer development and progression. The study consists of 493 breast cancer cases recruited from Nizam's Institute of Medical Sciences, Hyderabad, and 558 age-matched healthy female controls from rural and urban areas. Genomic DNA was isolated by non-enzymatic method. Genotyping was done by amplification refractory mutation system (ARMS-PCR) method. Genotypes were reconfirmed by sequencing and results were analyzed statistically. We have performed Insilco analysis to know the RNA secondary structure by using online tool m fold. The TT genotype and T allele frequencies of Rrp1B1307 T > C polymorphism were significantly elevated in breast cancer (chi (2); p = < 0.008) cases compared to controls under different genetic models. The presence of T allele had conferred 1.75-fold risk for breast cancer development (OR = 1.75; 95 % CI = 1.15-2.67). The frequency of TT genotype of Rrp1b 1307T > C polymorphism was significantly elevated in obese patients (chi (2); p = 0.008) and patients with advanced disease (chi (2); p = 0.01) and with increased tumor size (chi (2); p = 0.01). Moreover, elevated frequency of T allele was also associated with positive lymph node status (chi (2); p = 0.04) and Her2 negative receptor status (chi (2); p = 0.006). Presence of Rrp1b1307TT genotype and T allele confer strong risk for breast cancer development and progression.

Three centered hydrogen bonds of the type C=O...H(N)...X-C in diphenyloxamide derivatives involving halogens and a rotating CF3 group: NMR, QTAIM, NCI and NBO studies

The existence of three centered C=O...H(N)...X-C hydrogen bonds (H-bonds) involving organic fluorine and other halogens in diphenyloxamide derivatives has been explored by NMR spectroscopy and quantum theoretical studies. The three centered H-bond with the participation of a rotating CF3 group and the F...H-N intramolecular hydrogen bonds, a rare observation of its kind in organofluorine compounds, has been detected. It is also unambiguously established by a number of one and two dimensional NMR experiments, such as temperature perturbation, solvent titration, N-15-H-1 HSQC, and F-19-H-1 HOESY, and is also confirmed by theoretical calculations, such as quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) and non-covalent interaction (NCI).

Role of synergistic pi-pi stacking and X-H center dot center dot center dot Cl (X = C, N, O) H-bonding interactions in gelation and gel phase crystallization

The self-assembly of p-pyridyl-ended oligo-p-phenylenevinylenes (OPVs) in ethanol leads to the formation of either hollow or solid microrods. The corresponding protonated OPVs with n-butyl chains induce transparent gelation and also gel phase crystallization owing to various synergistic noncovalent interactions. The chloride ion-selective gelation, AIEE and stimuli responsiveness of the gel are also observed.

Proper holomorphic mappings of balanced domains in C-n

We extend a well-known result, about the unit ball, by H. Alexander to a class of balanced domains in . Specifically: we prove that any proper holomorphic self-map of a certain type of balanced, finite-type domain in , is an automorphism. The main novelty of our proof is the use of a recent result of Opshtein on the behaviour of the iterates of holomorphic self-maps of a certain class of domains. We use Opshtein's theorem, together with the tools made available by finiteness of type, to deduce that the aforementioned map is unbranched. The monodromy theorem then delivers the result.

Microwave Spectrum of Hexafluoroisopropanol and Torsional Behavior of Molecules with a CF3-C-CF3 Group

This paper presents the first microwave spectroscopic investigation on hexafluoroisopropanol (HFIP). A pulsed nozzle Fourier transform microwave spectrometer has been used to determine the rotational constants for HFIP as A = 2105.12166(18) MHz, B = 1053.99503(12) MHz, and C = 932.33959(13) MHz. In addition, five isotopologues of HFIP have been observed experimentally to determine the accurate structure of HFIP. The observed spectrum could be assigned to the most stable conformer of HFIP, called antiperiplanar. Available spectroscopic information and ab initio calculations on five prototype molecules helped in exploring the torsional behavior of molecules having a CF3-C-CF3 group. Two-dimensional potential energy surfaces have been analyzed for all molecules, which explained the presence/absence of doubling in the rotational transitions. With the help of natural bond orbital (NBO) analysis, reasons for the conformational preference of HFIP have been explained.

GBNV encoded movement protein (NSm) remodels ER network via C-terminal coiled coil domain

Plant viruses exploit the host machinery for targeting the viral genome-movement protein complex to plasmodesmata (PD). The mechanism by which the non-structural protein m (NSm) of Groundnut bud necrosis virus (GBNV) is targeted to PD was investigated using Agrobacterium mediated transient expression of NSm and its fusion proteins in Nicotiana benthamiana. GFP:NSm formed punctuate structures that colocalized with mCherry:plasmodesmata localized protein la (PDLP la) confirming that GBNV NSm localizes to PD. Unlike in other movement proteins, the C-terminal coiled coil domain of GBNV NSm was shown to be involved in the localization of NSm to PD, as deletion of this domain resulted in the cytoplasmic localization of NSm. Treatment with Brefeldin A demonstrated the role of ER in targeting GFP NSm to PD. Furthermore, mCherry:NSm co-localized with ER-GFP (endoplasmic reticulum targeting peptide (HDEL peptide fused with GFP). Co-expression of NSm with ER-GFP showed that the ER-network was transformed into vesicles indicating that NSm interacts with ER and remodels it. Mutations in the conserved hydrophobic region of NSm (residues 130-138) did not abolish the formation of vesicles. Additionally, the conserved prolines at positions 140 and 142 were found to be essential for targeting the vesicles to the cell membrane. Further, systematic deletion of amino acid residues from N- and C-terminus demonstrated that N-terminal 203 amino acids are dispensable for the vesicle formation. On the other hand, the C-terminal coiled coil domain when expressed alone could also form vesicles. These results suggest that GBNV NSm remodels the ER network by forming vesicles via its interaction through the C-terminal coiled coil domain. Interestingly, NSm interacts with NP in vitro and coexpression of these two proteins in planta resulted in the relocalization of NP to PD and this relocalization was abolished when the N-terminal unfolded region of NSm was deleted. Thus, the NSm interacts with NP via its N-terminal unfolded region and the NSm-NP complex could in turn interact with the ER membrane via the C-terminal coiled coil domain of NSm to form vesicles that are targeted to PD and there by assist the cell to cell movement of the viral genome complex. (C) 2015 Elsevier Inc. All rights reserved.

Sulfenyiation of beta-Diketones Using C-H Functionalization Strategy

Sulfenylation of beta-diketones is challenging as beta-diketones undergo deacylation after sulfenylation in the reaction medium. The sulfenylation of beta-diketones without deacylation under metal-free conditions at ambient temperature via a cross dehydrogenative coupling (CDC) strategy is reported. The resultant products can be further manipulated to form alpha,alpha-disubstituted beta-diketones and pyrazoles.

Different Modes of Transactivation of Bacteriophage Mu Late Promoters by Transcription Factor C

Transactivator protein C is required for the expression of bacteriophage Mu late genes from lys, I, P and mom promoters during lytic life cycle of the phage. The mechanism of transcription activation of mom gene by C protein is well understood. C activates transcription at Pmom by initial unwinding of the promoter DNA, thereby facilitating RNA polymerase (RNAP) recruitment. Subsequently, C interacts with the (sic) subunit of RNAP to enhance promoter clearance. The mechanism by which C activates other late genes of the phage is not known. We carried out promoter-polymerase interaction studies with all the late gene promoters to determine the individual step of C mediated activation. Unlike at P-mom, at the other three promoters, RNAP recruitment and closed complex formation are not C dependent. Instead, the action of C at P-lys, P-I, and P-P is during the isomerization from closed complex to open complex with no apparent effect at other steps of initiation pathway. The mechanism of transcription activation of mom and other late promoters by their common activator is different. This distinction in the mode of activation (promoter recruitment and escape versus isomerization) by the same activator at different promoters appears to be important for optimized expression of each of the late genes.

The X-C---Y (X = O/F, Y = O, S, F, Cl, Br, N, P,) Carbon bond and hydrophobic interactions

While the tetrahedral face of methane has an electron rich centre and can act as a hydrogen bond acceptor, substitution of one of its hydrogens with some electron withdrawing group (such as -F/OH) can make the opposite face electron deficient. Electrostatic potential calculations confirm this and high level quantum calculations show interactions between the positive face of methanol/methyl fluoride and electron rich centers of other molecules such as H2O. Analysis of the wave functions of atoms in molecules shows the presence of an unusual C···Y interaction, which could be called 'carbon bonding'. NBO analysis and vibrational frequency shifts confirm the presence of this interaction. Given the properties of alkyl groups bonded to electronegative elements in biological molecules, such interactions could play a significant role, which is yet to be recognized. This and similar interactions could give an enthalpic contribution to what is called the 'hydrophobic interactions'.

Genetic diversity and proviral DNA load in different neural compartments of HIV-1 subtype C infection

In India, the low prevalence of HIV-associated dementia (HAD) in the Human immunodeficiency virus type 1 (HIV-1) subtype C infection is quite paradoxical given the high-rate of macrophage infiltration into the brain. Whether the direct viral burden in individual brain compartments could be associated with the variability of the neurologic manifestations is controversial. To understand this paradox, we examined the proviral DNA load in nine different brain regions and three different peripheral tissues derived from ten human subjects at autopsy. Using a highly sensitive TaqMan probe-based real-time PCR, we determined the proviral load in multiple samples processed in parallel from each site. Unlike previously published reports, the present analysis identified uniform proviral distribution among the brain compartments examined without preferential accumulation of the DNA in any one of them. The overall viral DNA burden in the brain tissues was very low, approximately 1 viral integration per 1000 cells or less. In a subset of the tissue samples tested, the HIV DNA mostly existed in a free unintegrated form. The V3-V5 envelope sequences, demonstrated a brain-specific compartmentalization in four of the ten subjects and a phylogenetic overlap between the neural and non-neural compartments in three other subjects. The envelope sequences phylogenetically belonged to subtype C and the majority of them were R5 tropic. To the best of our knowledge, the present study represents the first analysis of the proviral burden in subtype C postmortem human brain tissues. Future studies should determine the presence of the viral antigens, the viral transcripts, and the proviral DNA, in parallel, in different brain compartments to shed more light on the significance of the viral burden on neurologic consequences of HIV infection.