Diversity in Functional Organization of Class I and Class II Biotin Protein Ligase

The cell envelope of Mycobacterium tuberculosis (M. tuberculosis) is composed of a variety of lipids including mycolic acids, sulpholipids, lipoarabinomannans, etc., which impart rigidity crucial for its survival and pathogenesis. Acyl CoA carboxylase (ACC) provides malonyl-CoA and methylmalonyl-CoA, committed precursors for fatty acid and essential for mycolic acid synthesis respectively. Biotin Protein Ligase (BPL/BirA) activates apo-biotin carboxyl carrier protein (BCCP) by biotinylating it to an active holo-BCCP. A minimal peptide (Schatz), an efficient substrate for Escherichia coli BirA, failed to serve as substrate for M. tuberculosis Biotin Protein Ligase (MtBPL). MtBPL specifically biotinylates homologous BCCP domain, MtBCCP87, but not EcBCCP87. This is a unique feature of MtBPL as EcBirA lacks such a stringent substrate specificity. This feature is also reflected in the lack of self/promiscuous biotinylation by MtBPL. The N-terminus/HTH domain of EcBirA has the selfbiotinable lysine residue that is inhibited in the presence of Schatz peptide, a peptide designed to act as a universal acceptor for EcBirA. This suggests that when biotin is limiting, EcBirA preferentially catalyzes, biotinylation of BCCP over selfbiotinylation. R118G mutant of EcBirA showed enhanced self and promiscuous biotinylation but its homologue, R69A MtBPL did not exhibit these properties. The catalytic domain of MtBPL was characterized further by limited proteolysis. Holo-MtBPL is protected from proteolysis by biotinyl-59 AMP, an intermediate of MtBPL catalyzed reaction. In contrast, apo-MtBPL is completely digested by trypsin within 20 min of co-incubation. Substrate selectivity and inability to promote self biotinylation are exquisite features of MtBPL and are a consequence of the unique molecular mechanism of an enzyme adapted for the high turnover of fatty acid biosynthesis.

Self-assembly of neutral and cationic Pd-II organometallic molecular rectangles: synthesis, characterization and nitroaromatic sensing

Design and synthesis of three novel 2 + 2] self-assembled molecular rectangles 1-3 via coordination driven self-assembly of predesigned Pd(II) ligands is reported. 1,8-Diethynylanthracene was assembled with trans-Pd(PEt3)(2)Cl-2 in the presence of CuCl catalyst to yield a neutral rectangle 1 via Pd-C bond formation. Complex 1 represents the first example of a neutral molecular rectangle obtained via C-Pd coordination driven self-assembly. A new Pd-2(II) organometallic building block with 180 degrees bite-angle 1,4-bistrans-(ethynyl)Pd(PEt3)(2)(NO3)] benzene (M-2) containing ethynyl functionality was synthesized in reasonable yield by employing Sonagashira coupling reaction. Self-assembly of M-2 with two organic clip-type donors (L-2-L-3) afforded 2 + 2] self-assembled molecular rectangles 2 and 3, respectively L-2 = 1,8-bis(4-pyridylethynyl) anthracene; L-3 = 1,3-bis(3-pyridyl) isophthalamide]. The macrocycles 1-3 were fully characterized by multinuclear NMR and ESI-MS spectroscopic techniques, and in case of 1 the structure was unambiguously determined by single crystal X-ray diffraction analysis. Incorporation of Pd-ethynyl bonds helped to make the assemblies p-electron rich and fluorescent in nature. Complexes 1-2 showed quenching of fluorescence intensity in solution in presence of nitroaromatics, which are the chemical signatures of many commercially available explosives.

Ce0.98Pd0.02O2-delta: Recyclable, ligand free palladium(II) catalyst for Heck reaction

Palladium substituted in cerium dioxide in the form of a solid solution, Ce-0.98 Pd-0.02 O-1.98 is a new heterogeneous catalyst which exhibits high activity and 100% trans-selectivity for the Heck reactions of aryl bromides including heteroaryls with olefins. The catalytic reactions work without any ligand. Nano-crystalline Ce-0.98 Pd-0.02 O-1.98 is prepared by solution combustion method and Pd is in +2 state. The catalyst can be separated, recovered and reused without significant loss in activity.

Physicochemical studies of (o-vanillin thiosemicarbazonato)-nickel(Ii) chelate

Five- and six-membered rings result from the chelation of nickel(II) by the dibasic tridentate Schiff base ligand, o-vanillin thiosemicarbazone(o-VTSC), a new chelate prepared and characterized. The structural results are discussed in the light of spectroscopic and other data.

Calcium/Calmodulin Dependent Protein Kinase II Bound to NMDA Receptor 2B Subunit Exhibits Increased ATP Affinity and Attenuated Dephosphorylation

Calcium/calmodulin dependent protein kinase II (CaMKII) is implicated to play a key role in learning and memory. NR2B subunit of N-methyl-D-aspartate receptor (NMDAR) is a high affinity binding partner of CaMKII at the postsynaptic membrane. NR2B binds to the T-site of CaMKII and modulates its catalysis. By direct measurement using isothermal titration calorimetry (ITC), we show that NR2B binding causes about 11 fold increase in the affinity of CaMKII for ATP gamma S, an analogue of ATP. ITC data is also consistent with an ordered binding mechanism for CaMKII with ATP binding the catalytic site first followed by peptide substrate. We also show that dephosphorylation of phospho-Thr(286)-alpha-CaMKII is attenuated when NR2B is bound to CaMKII. This favors the persistence of Thr(286) autophosphorylated state of CaMKII in a CaMKII/phosphatase conjugate system in vitro. Overall our data indicate that the NR2B- bound state of CaMKII attains unique biochemical properties which could help in the efficient functioning of the proposed molecular switch supporting synaptic memory.

Star formation in giant extragalactic H II regions

Star formation properties in Giant Extragalactic H II Regions (GEHRs) are investigated using optical photometry and evolutionary population synthesis models. Photometric data in $BVR$ bands and in the emission line of H-alpha are obtained by CCD imaging at Vainu Bappu Observatory, Kavalur. Aperture photometry is performed for 180 GEHRs in galaxies NGC 1365, 1566, 2366, 2903, 2997, 3351, 4303, 4449, 4656 and 5253. Thirty six of these GEHRs having published spectroscopic data are studied for star formation properties. The population synthesis model is constructed based on Maeder's stellar evolutionary and Kurucz stellar atmosphere models, to synthesize observational quantities of embedded clusters in GEHRs. The observed H-alpha luminosity is a measure of the number of massive stars while the contribution to BVR bands is from intermediate mass (5-15 solar mass) stars when the cluster is young and from evolving supergiants when the cluster is old (age >/= 6~Myr). Differential reddening between gas and embedded stars is essential to constrain the dereddened cluster colors within the range of youngest clusters. Obscuring dust closely associated with gas, which is distributed in filaments and clumps, as in the case of 30 Doradus, is the most likely configuration giving rise to net reduction of extinction towards stars. The fraction of the stellar photons escaping the nebula unattenuated is estimated to be 50%. GEHRs are rarely found to be simple systems containing stars from single generation. In the present sample such regions in addition to being older than 3~Myr, have their Lyman continuum luminosity reduced by as much as 60%, compared to the observed $B$ band luminosity for a normal IMF. The missing ionizing photons may be escaping the nebula, leading to the ionization of extra-H II region ionized medium. Co-existence of young (age dences for the co-existence of young and old populations in giant star forming complexes. Triggering of star formation from earlier bursts is the most likely cause of new generation of stars, and may be a common phenomenon in GEHRs. Spatial separation between the young and old stars (~30 pc) had been earlier reported in 30 Doradus. Thus GEHRs in nearby galaxies share many of the properties shown by 30 Dor, the nearest GEHR. (SECTION: Dissertation Summaries)

Synthesis based on cyclohexadienes. Part 15. Total synthesis of (±)-prezizaene, (±)-prezizanol and (±)-jinkohol II

A new methodology for the synthesis of the complex ring system tricyclo[6.2.1.0(1.5)]undecane. present in the zizaene group of sesquiterpenes, is described. Acid-catalysed rearrangement of the endo alcohol 20 afforded the enone 12, which was transformed stereoselectively into the key intermediate. (+/-)-norprezizanone 10. The features of the synthesis are the transformation of a bicycle[2.2.2] octane framework into a bicycle[3.2.1] octane system by an acid-catalysed rearrangement and a stereoselective conjugate addition of a methyl group on an alpha,beta-unsaturated keto ester at -100 degrees C. Norprezizanone was converted into the sesquiterpenes (+/-)-prezizanol 5 and(+/-)-prezizaene 4. The first total synthesis of (+/-)-jinkohol II 6 is also presented.

Constructions of 2D-Metallamacrocycles Using Half-Sandwich Ru-2(II) Precursors: Synthesis, Molecular Structures, and Self-Selection for a Single Linkage Isomer

Coordination-driven self-assembly of oxalato-bridged half-sandwich p-cymene ruthenium complex Ru-2(mu-eta(4)-C2O4)(MeOH)(2)(eta(6)-p-cymene)(2)] (O3SCF3)(2) (1a) with several ditopic donors (L-a-L-d) in methanol affords a series of bi- and tetranuclear metallamacrocycles (2a and 3-5). Similarly, the combination of 2,5-dihydroxy-1,4-benzoquinonato (dhbq)-bridged binuclear complex Ru-2(mu-eta(4)-C6H2O4)(MeOH)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (1b) with a flexible bidentate amide linker (L-a) in 1:1 molar ratio gave the corresponding tetranuclear complex 2b. All the macrocycles were isolated as their triflate salts in high yields and were fully characterized by various spectroscopic techniques. Finally, the molecular structures of all the assemblies were determined unambiguously by single-crystal X-diffraction analysis. Interestingly, the combination of acceptor 1a or 1b with an unsymmetrical linear ditopic donor L-a results in a self-sorted linkage isomeric (head-to-tail) macrocycle (2a or 2b) despite the possibility of formation of two different isomeric macrocycles (head-to-head or head-to-tail) due to different connectivity of the donor. Molecular structures of the complexes 2a and 2b showed tetranuclear rectangular geometry with dimensions of 5.51 angstrom x 13.29 angstrom for 2a and 7.91 angstrom x 13.46 angstrom for 2b. In both cases, two binuclear Ru-2(II) building blocks are connected by a mu-N-(4-pyridyl)isonicotinamide donor in a head-to-tail fashion. Surprisingly, the macrocycle 2a loses one counteranion and cocrystallizes with monodeprotonated 1,3,5-trihydroxybenzene via strong intermolecular pi-pi stacking and hydrogen bonding. The tweezer complex 3 showed strong fluorescence in solution, and it showed fluorescence sensing toward nitroaromatic compounds. A fluorescence study demonstrated a marked quenching of the initial fluorescence intensity of the macrocycle 3 upon gradual addition of trinitrotoluene and exhibits significant fluorescence quenching response only for nitroaromatic compounds compared to various other aromatic compounds tested.

(+/-)-cis-Dichloro[P-(isopropylamino)-dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine](triethylphosphine)platinum(II) dichloromethane solvate

In the racemic title compound, [PtCl2(C23H20NO2P)-(C6H15P)].CH2Cl2, the platinum(II) ion, which has approximately square-planar coordination geometry, is coordinated to two different monophosphorus ligands in a cis arrangement along with two chloride ions. A significant shortening of the P-N bond [1.604(7) Angstrom] relative to that in phosphinoamines and their complexes was observed.

Brownian dynamics simulation of dense binary colloidal mixtures. II. Translational and bond-orientational order

We report the Brownian dynamics simulation results on the translational and bond-angle-orientational correlations for charged colloidal binary suspensions as the interparticle interactions are increased to form a crystalline (for a volume fraction phi = 0.2) or a glassy (phi = 0.3) state. The translational order is quantified in terms of the two- and four-point density autocorrelation functions whose comparisons show that there is no growing correlation length near the glass transition. The nearest-neighbor orientational order is determined in terms of the quadratic rotational invariant Q(l) and the bond-orientational correlation functions g(l)(t). The l dependence of Q(l) indicates that icosahedral (l = 6) order predominates at the cost of the cubic order (l = 4) near the glass as well as the crystal transition. The density and orientational correlation functions for a supercooled liquid freezing towards a glass fit well to the streched-exponential form exp[-(t/tau)(beta)]. The average relaxation times extracted from the fitted stretched-exponential functions as a function of effective temperatures T* obey the Arrhenius law for liquids freezing to a crystal whereas these obey the Vogel-Tamman-Fulcher law exp[AT(0)*/(T* - T-0*)] for supercooled Liquids tending towards a glassy state. The value of the parameter A suggests that the colloidal suspensions are ''fragile'' glass formers like the organic and molecular liquids.

Low-temperature structure of two copper-based precursors for MOCVD: Aquabis(tert-butyl acetoacetato)copper(II) and Bis(dipivaloylmethanido)copper(II)

The Cu atoms in aquabis(tert-butyl acetoacetato)copper(II),[Cu(C8H13O3)(2)(H2O)], and bis(dipivaloylmethanido)copper(II), [Cu(C11H19O2)(2)], adopt square-pyramidal and planar conformations, respectively, with average Cu--O distances of 1.933 Angstrom in the former (not including the water ligand) and 1.892 Angstrom in the latter. It is interesting to note that the lability of the tert-butyl and methyl groups in both structures, which renders even the location of the terminal C atoms difficult, is reduced at T = 130 K, enabling location of all the protons in the difference Fourier map.

Stabilisation of unusual simultaneous binding of four cytosine nucleobases to copper(II) by a novel network of bifurcated hydrogen bonding

The crystal structure of tetrakis(cytosine)copper(II) perchlorate dihydrate has been determined. All the hydrogen atoms were obtained from Fourier-difference synthesis. The geometry around. copper is a bicapped octahedron (4 + 2 + 2*). The adjacent cytosine rings are oriented head-to-tail with respect to each other and are roughly at right angles to the co-ordination plane. The exocyclic oxo groups form an interligand, intracomplex hydrogen-bonding network above and below the co-ordination plane with the exocyclic amino groups of alternate cytosine bases. The EPR and electronic spectra are consistent with the retention of the solid-state structure in solution. The steric effect of the C(2)=O group of cytosine is offset by the presence of the intracomplex hydrogen-bonding network. The trend in Ei values of Cu-II-Cu-I couples for 1.4 complexes of cytosine, cytodine, pyridine, 2-methylpyridine and N-methylimidazole suggests that both steric effects and pi-delocalization in imidazole and pyridine ligands and the steric effect of C(2)=O in pyrimidine ligands are important in stabilising Cu-I relative to Cu-II.

Synthesis, characterisation and superoxide dismutase activity of a manganese(II) complex

A potent superoxide dismutase mimic; Mn-II(HL)(2) [H(2)L = 2,6-bis(benzimidazol-2-yl)pyridine] has been synthesised and characterised by its crystal structure determination and EPR spectroscopy.

Structure of diaquadichlorobis(hydrazinium)iron(II) dichloride

[Fe(N2H5)2(H2O)2Cl2].Cl2, M(r) = 299.65, monoclinic, P2(1)/c, a = 8.027 (1), b = 5.725 (2), c = 11.430 (2) angstrom, beta = 97.08 (1)-degrees, V = 521.3 (2) angstrom 3, Z = 2, D(m) = 1.92, D(x) = 1.910 g cm-3, lambda(Mo K-alpha) = 0.71069 angstrom, mu = 24.5 cm-1, F(000) = 304, T = 295 K, final R = 0.0242 and wR = 0.0292 for 1411 significant [F(o) > 5.0-sigma(F(o))] reflections. The crystal contains discrete Cl- ions and complex [Fe(N2H5)2(H2O)2Cl2]2+ cations. In the complex cation, the Fe atom is bonded to two hydrazinium cations, two Cl atoms and two water molecules. The coordinated atoms are trans to each other. The ions are connected by both N-H...Cl and O-H...Cl type hydrogen bonds.