H2L 5765834

Differences in nuclearity, molecular shapes, and coordination modes of azide in the complexes of Cd(II) and Hg(II) with a "metalloligand" [CuL] (H2L = N,N'-bis(salicylidene)-1,3-propanediamine): characterization in solid and in solutions, and theoretical calculations.[Pubmed:23131113]

Inorg Chem. 2012 Nov 19;51(22):12407-18.

Two new heterometallic copper(II)-mercury(II) complexes [(CuL)Hg(N3)2]n (1) and [(CuL)2Hg(N3)2] (2) and one copper(II)-cadmium(II) complex [(CuL)2Cd(N3)2] (3) have been synthesized using "metalloligand" [CuL] (where H2L = N,N'-bis(salicylidene)-1,3-propanediamine) and structurally characterized. Complex 1 is a one-dimensional (1D) helical coordination polymer constructed by the joining of the dinuclear [(CuL)Hg(N3)2] units through a single mu-l,l azido bridge. In the dinuclear unit the Hg(II) is bonded with two phenoxido oxygen atoms of "metalloligand" [CuL] and two nitrogen atoms of azido ligands. Complex 2 is a linear trinuclear entity, in which two terminal "metalloligands" [CuL] are coordinated to central Hg(II) through double phenoxido bridges. The azido ligands link the central mercury atom with the terminal copper atoms via mu-l,3 bridges. In contrast, the trinuclear complex 3 is bent. Here, in addition to two double phenoxido bridges, central Cd(II) is bonded to two mutually cis nitrogen atoms of two terminal azido ligands. The variation in the coordination modes of the azido ligand seems to be responsible for the different molecular shapes of 2 and 3. Interestingly, bond distances between the Hg atoms and the central nitrogen atom of the azido ligands are 2.790(4) and 2.816(5) A in 1 and 2.823(4) A in 2. These bond distances are significantly less than the sum of van der Waals radii of mercury (2.04 A) and nitrogen (1.55 A) and considerably longer than the sum of their covalent radii (2.03 A). However the distances are similar to reported Hg-N bond distances of some Hg(II) complexes. Therefore, we have performed a theoretical density functional theory study to know whether there is any interaction between the central nitrogen atom of the azido ligand and the mercury atoms. We have used the Bader's "atoms-in-molecules", energetic and orbital analyses to conclude that such interaction does not exist. The probable reason for different molecular shapes observed in trinuclear complexes of 2 and 3 also has been studied and explained by theoretical calculations and using the CSD. Electronic spectra, EPR spectra and ESI mass spectra show that all three complexes lose their solid state identity in solution.

Programmable self-assembly of water-soluble organo-heterometallic cages [M12M'4L12] using 3-(3,5-dimethyl-1H-pyrazol-4-yl)pentane-2,4-dione (H2L).[Pubmed:28361135]

Chem Commun (Camb). 2017 Apr 11;53(30):4238-4241.

A bifunctional ligand H2L featuring primary (pyrazole) and secondary (acetylacetone) coordination sites was preferentially reacted with dimetallic [M2(NO3)2](NO3)2 linkers at the pyrazolyl end of H2L, giving rise to dimetallic corners. Subsequently, the corners serve as the secondary site with M' to form water-soluble organo-heterometallic [M12M'4L12] cages in a stepwise mode.

Use of metalloligands [CuL] (H2L = salen type di-Schiff bases) in the formation of heterobimetallic copper(II)-uranyl complexes: photophysical investigations, structural variations, and theoretical calculations.[Pubmed:23786416]

Inorg Chem. 2013 Jul 1;52(13):7508-23.

Five heterobimetallic copper(II)-uranium(VI) complexes [(CuL(1))UO2(NO3)2] (1), [{CuL(1)(CH3CN)}UO2(NO3)2] (2), [{CuL(1)(CH3COCH3)}UO2(NO3)2] (3), [{CuL(2)(CH3CN)}UO2(NO3)2](4), and [{CuL(2)(CH3COCH3)}UO2(NO3)2][{CuL(2)}UO2(NO3)2] (5) have been synthesized by reacting the Cu(II)-derived metalloligands [CuL(1)] and [CuL(2)] (where, H2L(1) = N,N'-bis(alpha-methylsalicylidene)-1,3-propanediamine and H2L(2) = N,N'-bis(salicylidene)-1,3-propanediamine) with UO2(NO3)2.6H2O in 1:1 ratio by varying the reaction temperature and solvents. Absorption and fluorescence quenching experiments (steady-state and time-resolved) indicate the formation of 1:1 ground-state charge transfer copper(II)-uranium(VI) complexes in solution. X-ray single-crystal structure reveals that each complex contains diphenoxido bridged Cu(II)-U(VI) dinuclear core with two chelated nitrato coligands. The complexes are solvated (acetonitrile or acetone) in the axial position of the Cu(II) in different manner or desolvated. The supramolecular interactions that depend upon the co-ordinating metalloligands seem to control the solvation. In complexes 2 and 3 a rare NO3(-)...NO3(-) weak interaction plays an important role in forming supramolecular network whereas an uncommon U horizontal lineO...NO3(-) weak interaction helps to self-assemble heterobinuclear units in complex 5. The significance of the noncovalent interactions in terms of energies and geometries has been analyzed using theoretical calculations.

Influence of the central metal ion in controlling the self-assembly and magnetic properties of 2D coordination polymers derived from [(NiL)2M](2+) nodes (M = Ni, Zn and Cd) (H2L = salen-type di-Schiff base) and dicyanamide spacers.[Pubmed:25418864]

Dalton Trans. 2015 Jan 21;44(3):1292-302.

Three new 2D coordination polymers (CPs) (2)infinity[(NiL)2Ni(mu1,5-N(CN)2)2]n (), (2)infinity[(NiL)2Cd(mu1,5-N(CN)2)2]n () and (2)infinity[(NiL)2Zn(mu1,5-N(CN)2)2]n () have been synthesized by reacting a [NiL] "metalloligand" (where H2L = N,N'-bis(salicylidene)-1,3-propanediamine) with three different metal(ii) (Ni, Cd and Zn) perchlorates and sodium dicyanamide, with identical molar ratios of the reactants. All three products have been characterized by IR and UV-Vis spectroscopies, elemental analyses, powder and single crystal X-ray diffraction and variable temperature magnetic measurements. The isomorphous compounds and consist of similar [(NiL)2M(mu1,5-N(CN)2)] (M = Ni for and Cd for ) angular trinuclear units in which two terminal "metalloligands" [NiL] coordinate to the central nickel(ii) (in ) or cadmium(ii) (in ) ion through phenoxido oxygen atoms. The mu1,5-bridging dicyanamido spacers connect the central Ni(ii) or Cd(ii) of one node to terminal Ni(ii) of two different nodes giving rise to 2D CPs. Compound also contains trinuclear units with the same formula as those of and : [(NiL)2M(mu1,5-N(CN)2)] (M = Zn in ). The main differences are that these units are linear in and the dicyanamide spacers link only the nickel atoms of neighbouring nodes. As in and , these trinuclear units are connected to four other units via four mu1,5-bridging dicyanamido ligands, giving rise to 2D CP with a similar topology: a uninodal 4-connected underlying net with the sql (Shubnikov tetragonal plane net) topology and (4(4).6(2)) point symbol. The magnetic properties show the presence of moderate intra-trimer antiferromagnetic interactions in (J = -12.9 cm(-1)) and weak antiferromagnetic interactions between the terminal Ni(ii) ions in (J = -2.4 cm(-1)). In the Ni(ii) ions are well isolated by the central Zn(ii) ion and accordingly, only a very weak antiferromagnetic interaction through the single mu1,5-bridging dicyanamido ligands is observed (J = -0.44 cm(-1), D = -3.9 cm(-1)).

2D binary QSAR modeling of LPA3 receptor antagonism.[Pubmed:20356772]

J Mol Graph Model. 2010 Jun;28(8):828-33.

A structurally diverse dataset of 119 compounds was used to develop and validate a 2D binary QSAR model for the LPA(3) receptor. The binary QSAR model was generated using an activity threshold of greater than 15% inhibition at 10 microM. The overall accuracy of the model on the training set was 82%. It had accuracies of 55% for active and 91% for inactive compounds, respectively. The model was validated using an external test set of 10 compounds. The accuracy on the external test set was 60% overall, identifying three out of seven actives and all three inactive compounds. This model was combined with similarity searching to rapidly screen libraries and select 14 candidate LPA(3) antagonists. Experimental assays confirmed 13 of these (93%) met the 15% inhibition threshold defining actives. The successful application of the model to select candidates for screening demonstrates the power of this binary QSAR model to prioritize compound selection for experimental consideration.

Aiming drug discovery at lysophosphatidic acid targets.[Pubmed:20735414]

Br J Pharmacol. 2010 Sep;161(2):241-70.

Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is the prototype member of a family of lipid mediators and second messengers. LPA and its naturally occurring analogues interact with G protein-coupled receptors on the cell surface and a nuclear hormone receptor within the cell. In addition, there are several enzymes that utilize LPA as a substrate or generate it as a product and are under its regulatory control. LPA is present in biological fluids, and attempts have been made to link changes in its concentration and molecular composition to specific disease conditions. Through their many targets, members of the LPA family regulate cell survival, apoptosis, motility, shape, differentiation, gene transcription, malignant transformation and more. The present review depicts arbitrary aspects of the physiological and pathophysiological actions of LPA and attempts to link them with select targets. Many of us are now convinced that therapies targeting LPA biosynthesis and signalling are feasible for the treatment of devastating human diseases such as cancer, fibrosis and degenerative conditions. However, successful targeting of the pathways associated with this pleiotropic lipid will depend on the future development of as yet undeveloped pharmacons.

Unique ligand selectivity of the GPR92/LPA5 lysophosphatidate receptor indicates role in human platelet activation.[Pubmed:19366702]

J Biol Chem. 2009 Jun 19;284(25):17304-19.

Lysophosphatidic acid (LPA) is a ligand for LPA(1-3) of the endothelial differentiation gene family G-protein-coupled receptors, and LPA(4-8) is related to the purinergic family G-protein-coupled receptor. Because the structure-activity relationship (SAR) of GPR92/LPA(5) is limited and whether LPA is its preferred endogenous ligand has been questioned in the literature, in this study we applied a combination of computational and experimental site-directed mutagenesis of LPA(5) residues predicted to interact with the headgroup of LPA. Four residues involved in ligand recognition in LPA(5) were identified as follows: R2.60N mutant abolished receptor activation, whereas H4.64E, R6.62A, and R7.32A greatly reduced receptor activation. We also investigated the SAR of LPA(5) using LPA analogs and other non-lysophospholipid ligands. SAR revealed that the rank order of agonists is alkyl glycerol phosphate > LPA > farnesyl phosphates >> N-arachidonoylglycine. These results confirm LPA(5) to be a bona fide lysophospholipid receptor. We also evaluated several compounds with previously established selectivity for the endothelial differentiation gene receptors and found several that are LPA(5) agonists. A pharmacophore model of LPA(5) binding requirements was developed for in silico screening, which identified two non-lipid LPA(5) antagonists. Because LPA(5) transcripts are abundant in human platelets, we tested its antagonists on platelet activation and found that these non-lipid LPA(5) antagonists inhibit platelet activation. The present results suggest that selective inhibition of LPA(5) may provide a basis for future anti-thrombotic therapies.