New symmetrical dinucleating ligand based assembly of bridged dicopper(II) and dizinc(II) centers: Synthesis, structure, spectroscopy, magnetic properties and glycoside hydrolysis

Two dinuclear copper(II) complexes Li(H2O)(3)(CH3OH)](4)Cu2Br4]Cu-2(cpdp)(mu-O2CCH3)](4)(OH)(2) (1), Cu (H2O)(4)]Cu-2(cpdp)(mu-O2CC6H5)](2)Cl-2 center dot 5H(2)O (2), and a dinuclear zinc(II) complex Zn-2(cpdp)(mu-O2CCH3)] (3) have been synthesized using pyridine and benzoate functionality based new symmetrical dinucleating ligand, N, N'-Bis2-carboxybenzomethyl]-N, N'-Bis2-pyridylmethyl]-1,3-diaminopropan-2-ol (H(3)cpdp). Complexes 1, 2 and 3 have been synthesized by carrying out reaction of the ligand H3cpdp with stoichiometric amounts of Cu-2(O2CCH3)(4)(H2O)(2)], CuCl2 center dot 2H(2)O/C6H5COONa, and Zn(CH3COO)(2)center dot 2H(2)O, respectively, in methanol in the presence of NaOH at ambient temperature. Characterizations of the complexes have been done using various analytical techniques including single crystal X-ray structure determination. The X-ray crystal structure analyses reveal that the copper(II) ions in complexes 1 and 2 are in a distorted square pyramidal geometry with Cu-Cu separation of 3.455(8) angstrom and 3.492(1)angstrom, respectively. The DFT optimized structure of complex 3 indicates that two zinc(II) ions are in a distorted square pyramidal geometry with Zn-Zn separation of 3.492(8)angstrom. UV-Vis and mass spectrometric analyses of the complexes confirm their dimeric nature in solution. Furthermore, H-1 and C-13 NMR spectroscopic investigations authenticate the integrity of complex 3 in solution. Variable-temperature (2-300 K) magnetic susceptibility measurements show the presence of antiferromagnetic interactions between the copper centers, with J = -26.0 cm(-1) and -23.9 cm(-1) ((H) over cap = -2JS(1)S(2)) in complexes 1 and 2, respectively. In addition, glycosidase-like activity of the complexes has been investigated in aqueous solution at pH similar to 10.5 by UV-Vis spectrophotometric technique using p-nitrophenyl-alpha-D-glucopyranoside (4) and p-nitrophenyl-beta-D-glucopyranoside (5) as model substrates. (C) 2015 Elsevier B.V. All rights reserved.

Mononuclear five-coordinate cobalt(II) complexes with N-4-coordinate pyrazole based ligand and pseudohalogens: synthesis, structures, DNA and protein binding study

A series of mononuclear five-coordinate cobalt(II) complexes, Co(dbdmp)(X)]Y, where dbdmp=N,N-diethyl-N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)ethane-1, 2-diamine, X=N-3(-)/NCO-/NCS- and Y=PF6-/BF4-/ClO4-, have been synthesized and characterized by microanalyses and spectroscopic techniques. Crystal structures of Co(N-3)(dbdmp)]PF6 (1), Co(N-3)(dbdmp)]ClO4 (3), Co(NCO)(dbdmp)]PF6 (4), Co(NCO)(dbdmp)]ClO4 (6), and Co(NCS)(dbdmp)]ClO4 (9) have been solved by single-crystal X-ray diffraction studies and showed that all the complexes have distorted trigonal bipyramidal geometry; PF6- counter anion containing complexes Co(N-3)(dbdmp)]PF6 and Co(NCO)(dbdmp)]PF6 have chiral space groups. The binding ability of synthesized complexes with CT-DNA and bovine serum albumin (BSA) has been studied by spectroscopic methods and viscosity measurements. The experimental results of absorption titration of cobalt(II) complexes with CT-DNA indicate that the complexes have ability to form adducts and they can stabilize the DNA helix. The cobalt(II) complexes exhibit good binding propensity to BSA protein.

Multivariate PLS Modeling of Apicomplexan FabD-Ligand Interaction Space for Mapping Target-Specific Chemical Space and Pharmacophore Fingerprints

Biomolecular recognition underlying drug-target interactions is determined by both binding affinity and specificity. Whilst, quantification of binding efficacy is possible, determining specificity remains a challenge, as it requires affinity data for multiple targets with the same ligand dataset. Thus, understanding the interaction space by mapping the target space to model its complementary chemical space through computational techniques are desirable. In this study, active site architecture of FabD drug target in two apicomplexan parasites viz. Plasmodium falciparum (PfFabD) and Toxoplasma gondii (TgFabD) is explored, followed by consensus docking calculations and identification of fifteen best hit compounds, most of which are found to be derivatives of natural products. Subsequently, machine learning techniques were applied on molecular descriptors of six FabD homologs and sixty ligands to induce distinct multivariate partial-least square models. The biological space of FabD mapped by the various chemical entities explain their interaction space in general. It also highlights the selective variations in FabD of apicomplexan parasites with that of the host. Furthermore, chemometric models revealed the principal chemical scaffolds in PfFabD and TgFabD as pyrrolidines and imidazoles, respectively, which render target specificity and improve binding affinity in combination with other functional descriptors conducive for the design and optimization of the leads.

Anomalous lifetime statistics of ligand-receptor binding in a tethered polymer system

In this paper, motivated by observations of non-exponential decay times in the stochastic binding and release of ligand-receptor systems, exemplified by the work of Rogers et al on optically trapped DNA-coated colloids (Rogers et al 2013 Soft Matter 9 6412), we explore the general problem of polymer-mediated surface adhesion using a simplified model of the phenomenon in which a single polymer molecule, fixed at one end, binds through a ligand at its opposite end to a flat surface a fixed distance L away and uniformly covered with receptor sites. Working within the Wilemski-Fixman approximation to diffusion-controlled reactions, we show that for a flexible Gaussian chain, the predicted distribution of times f(t) for which the ligand and receptor are bound is given, for times much shorter than the longest relaxation time of the polymer, by a power law of the form t(-1/4). We also show when the effects of chain stiffness are incorporated into this model (approximately), the structure of f(t) is altered to t(-1/2). These results broadly mirror the experimental trends in the work cited above.

Pd-Catalyzed Hydroborylation of Alkynes: A Ligand Controlled Regioselectivity Switch for the Synthesis of alpha- or beta-Vinylboronates

A ligand controlled selective hydroborylation of alkynes to alpha- or beta-vinylboronates has been developed using a Pd catalyst. The high alpha-selectivity displayed by this reaction can be switched to furnish beta-vinylboronates by altering the ligand from a trialkylphosphine to N-heterocyclic carbene. A variety of terminal alkynes are shown to furnish the corresponding alpha- or beta-vinylboronates in good to excellent selectivity and yield. The mechanistic studies suggest that the solvent is the proton source and bromobenzene functions as an important additive in driving this reaction forward.

Pd-Catalyzed Hydroborylation of Alkynes: A Ligand Controlled Regioselectivity Switch for the Synthesis of alpha- or beta-Vinylboronates

A ligand controlled selective hydroborylation of alkynes to alpha- or beta-vinylboronates has been developed using a Pd catalyst. The high alpha-selectivity displayed by this reaction can be switched to furnish beta-vinylboronates by altering the ligand from a trialkylphosphine to N-heterocyclic carbene. A variety of terminal alkynes are shown to furnish the corresponding alpha- or beta-vinylboronates in good to excellent selectivity and yield. The mechanistic studies suggest that the solvent is the proton source and bromobenzene functions as an important additive in driving this reaction forward.

Electrical and Plasmonic Properties of Ligand-Free Sn4+-Doped In2O3 (ITO) Nanocrystals

Sn4+-doped In2O3 (ITO) is a benchmark transparent conducting oxide material. We prepared ligand-free but colloidal ITO (8nm, 10% Sn4+) nanocrystals (NCs) by using a post-synthesis surface-modification reaction. (CH3)(3)OBF4 removes the native oleylamine ligand from NC surfaces to give ligand-free, positively charged NCs that form a colloidal dispersion in polar solvents. Both oleylamine-capped and ligand-free ITO NCs exhibit intense absorption peaks, due to localized surface plasmon resonance (LSPR) at around =1950nm. Compared with oleylamine-capped NCs, the electrical resistivity of ligand-free ITO NCs is lower by an order of magnitude (approximate to 35mcm(-1)). Resistivity over a wide range of temperatures can be consistently described as a composite of metallic ITO grains embedded in an insulating matrix by using a simple equivalent circuit, which provides an insight into the conduction mechanism in these systems.

Mycobacteria-responsive sonic hedgehog signaling mediates programmed death-ligand 1-and prostaglandin E-2-induced regulatory T cell expansion

CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are exploited by mycobacteria to subvert the protective host immune responses. The Treg expansion in the periphery requires signaling by professional antigen presenting cells and in particularly dendritic cells (DC). However, precise molecular mechanisms by which mycobacteria instruct Treg expansion via DCs are not established. Here we demonstrate that mycobacteria-responsive sonic hedgehog (SHH) signaling in human DCs leads to programmed death ligand-1 (PD-L1) expression and cyclooxygenase (COX)-2-catalyzed prostaglandin E-2 (PGE(2)) that orchestrate mycobacterial infection-induced expansion of Tregs. While SHH-responsive transcription factor GLI1 directly arbitrated COX-2 transcription, specific microRNAs, miR-324-5p and miR-338-5p, which target PD-L1 were downregulated by SHH signaling. Further, counter-regulatory roles of SHH and NOTCH1 signaling during mycobacterial-infection of human DCs was also evident. Together, our results establish that Mycobacterium directs a fine-balance of host signaling pathways and molecular regulators in human DCs to expand Tregs that favour immune evasion of the pathogen.

Amidinato- and triazenido-bridged binuclear complexes of palladium and platinum

The reaction of [M2Cl2(mu-Cl)(2)(PR3)(2)] (M=Pd or Pt; PR3=PEt3, PBu3, PMe2Ph, PMePh2) with lithium amidinate or sodium triazenide gave binuclear complexes containing amidinato- or triazenido-bridges, [M2Cl2(mu-ArNENAr)(2)(PR3)(2)] (E=CH, CMe or N). These complexes were characterized by elemental analysis and NMR (H-1, P-31 or Pt-195) data. The structures of two complexes, [(PdCl2)-Cl-2(mu-PhNC(Me)NPh)(2)(PMe2Ph)(2)] (10) and [Pt2Cl2(mu-PhNNNPh)(2)(PEt3)(2)] (11) were established by single crystal X-ray structural analyses. The Pt-195 NMR data Show coupling between two metal centers in the cis triazenido-bridged complex. The corresponding amidinate bridged complex does not show coupling. The role of the bridging ligand in mediating interaction between the metal centers is probed through Extended Huckel Theory (EHT) calculations. It is suggested that M-M interactions are primarily affected by the bridging ligands

Synthesis of some copper(II)-chelating (dialkylamino)pyridine amphiphiles and evaluation of their esterolytic capacities in cationic micellar media

Three new (dialkylamino)pyridine (DAAP)-based ligand amphiphiles 3-5 have been synthesized. All of the compounds possess a metal ion binding subunit in the form of a 2,6-disubstituted DAAP moiety. In addition, at least one ortho-CH2OH substituent is present in all the ligands. Complex formation by these ligands with various metal ions were examined under micellar conditions, but only complexes with Cu(II) ions showed kinetically potent esterolytic capacities under micellar conditions. Complexes with Cu(II) were prepared in host comicellar cetyltrimethylammonium bromide (CTABr) media at pH 7.6. Individual complexes were characterized by UV-visible absorption spectroscopy and electron paramagnetic resonance spectroscopy. These metallomicelles speed the cleavage of the substrates p-nitrophenyl hexanoate or p-nitrophenyl diphenyl phosphate. To ascertain the nature of the active esterolytic species, the stoichiometries of the respective Cu(II) complexes were determined from the kinetic version of Job's plot. In all the instances, 2:1 complex ligand/Cu(II) ion are the most kinetically competent species. The apparent pK(a) values of the Cu(II)-coordinated hydroxyl groups of the ligands 3, 4, and 5, in the comicellar aggregate, are 7.8, 8.0, and 8.0, respectively, as estimated from the rate constant vs pH: profiles of the ester cleavage reactions. The nucleophilic metallomicellar reagents and the second-order "catalytic" rate constants toward esterolysis of the substrate p-nitrophenyl hexanoate (at 25 degrees C, pH 7.6) are 37.5 for 3, 11.4 for 4, and 13.8 for 5. All catalytic systems comprising the coaggregates of 3, 4, or 5 and CTABr demonstrate turnover behavior in the presence of excess substrate.

Void Geometry Driven Spin Crossover in Zeolite-Encapsulated Cobalt Tris(bipyridyl) Complex Ion

The cobalt(II) tris(bipyridyl) complex ion encapsulated in zeolite-Y supercages exhibits a thermally driven interconversion between a low-spin and a high-spin state-a phenomenon not observed for this ion either in solid state or in solution. From a comparative study of the magnetism and optical spectroscopy of the encapsulated and unencapsulated complex ion, supported by molecular modeling, such spin behavior is shown to be intramolecular in origin. In the unencapsulated or free state, the [Co(bipy)(3)](2+) ion exhibits a marked trigonal prismatic distortion, but on encapsulation, the topology of the supercage forces it to adopt a near-octahedral geometry. An analysis using the angular overlap ligand field model with spectroscopically derived parameters shows that the geometry does indeed give rise to a low-spin ground state, and suggests a possible scenario for the spin state interconversion.

Solid state stacked trimers of 1,10-phenanthroline in a supramolecular tubular motif of C-methyl calix[4]resorcinarene

The self-assembly of bidentate ligand, 1,10-phenanthroline with C-methyl calix[4]resorcinarene (CMCR) in presence of coumarin results in a unique trimer stacking arrangement of phenanthroline molecules in a nanotubular motif generated by the supramolecular assembly of the host.

Synthesis, crystal structure and DNA cleavage activity of (aqua)bis(dipyridophenazine)copper(II) complex

A copper(II) complex of dipyridophenazine, viz., [Cu(dppz)(2)(H2O)](ClO4)(2) (I), has been prepared and structurally characterized by X-ray crystallography. The crystal structure of the complex shows a five-coordinate structure in which two N,N-donor dipyridophenazine (dppz) and one aqua ligand bind to the copper(II) center giving Cu-O and Cu-N bond distances in the range of 1.981(6) to 2.043(6) angstrom. The ESI-MS spectrum of 1 in MeCN shows a peak at m/z value of 313 (100%) indicating the dissociation of the aqua ligand in the solution phase. The complex is one-electron paramagnetic (mu(eff), 1.86 mu(B)). It displays a quasi-reversible Cu(II)/Cu(I) redox process at 0.096 V. The complex is an avid binder to CT DNA giving a binding constant value of 3.5 x 10(5) M-1. It shows significant hydrolytic cleavage of supercoiled pUC19 DNA in dark ill the absence of any external agents. The complex exhibits chemical nuclease activity oil treatment with 3-mercaptopropionic acid as a reducing agent forming hydroxyl radicals. Complex 1 is a model synthetic nuclease and hydrolase showing both modes of DNA cleavage under different reaction conditions. The DNA cleavage activity of 1 is significantly better than its phen analogue but similar to that of the bis-dpq complex.

Identification of amino groups in the carbohydrate binding activity of winged bean acidic agglutinin

Chemical modification studies reveal that the modification of amino groups in WBA II leads to a complete loss in the hemagglutinating and saccharide binding activities. Since WBA II is a dimeric molecule and contains two binding sites, one amino group in each of the binding sites is inferred to be essential for its activity. The presence of amino group which has a potential to form hydrogen bonded interactions with the ligand, substantiates our observation regarding the forces involved in WBA II-receptor and WBA II-simple sugar interactions.