M.V. Rajasekharan

Bis chelate Cu(II) complexes of dafone—synthesis, structural, EPR and optical spectral studies

Abstract Three examples of Cu(II) complexes with dafone, Cu(dafone)2Br2 (1), [Cu(dafone)2(H2O)2](NO3)2 (2) and [Cu(dafone)2(H2O)2](ClO4)2 (3) have been synthesized and characterized structurally and spectroscopically. All complexes show unsymmetric chelation of dafone with one Cu—N bond being much longer than the other. Powder diffuse reflectance spectra have been recorded for 1, 2 and the known complex, Cu(dafone)2Cl2 (4) and correlated with the molecular g-values for this relatively new type of Cu(II) chromophore. Compounds 1 and 2 were found to be sensitive to grinding leading to additional EPR signals for 1 and changes in the X-ray powder diffraction patterns.

Development of selective DprE1 inhibitors: Design, synthesis, crystal structure and antitubercular activity of benzothiazolylpyrimidine-5-carboxamides

Decaprenylphosphoryl-b-D-ribose 20-epimerase (DprE1) is a potential drug target for development of antitubercular agents. Structure based drug discovery approach yielded twenty novel derivatives of benzothiazolylpyrimidine-5-carboxamides (7a-t) which were synthesised by three component one pot reaction involving benzothiazolyl oxobutanamide, thiourea and substituted aromatic benzaldehydes. These derivatives were evaluated for antitubercular activity to determine MIC and compound 7a, 7e, 7f and 7o were found to be potentially active against Mycobacterium tuberculosis (H37Rv). Log P of these compounds was found to be between 2.0 and 3.0 making them suitable for oral dosing. DprE1 selectivity and pharmacokinetic studies were carried out for these compounds of which 7a and 7o were found to be highly selective and bioavailability was found to be above 52% by oral dose. Crystal structure of 7a was studied and molecular packing was determined, it exhibited a triclinic crystal lattice arrangement having hydrogen bonded dimeric arrangement. Drug receptor interactions were studied which exhibited docking in the active site of receptor with hydrogen bonding, hydrophobic interactions, vdW interactions with amino acid residues such as Cys387, Asn385, Lys418, Tyr314, Gln334 and Lys367 respectively. 3D QSAR analysis was carried out by kNN-MFA method to determine and develop theoretical model, best suitable model was found to be based on Simulated Annealing k-Neariest Neighbour Molecular Field Analysis (SA kNN-MFA). The model provided with hydrophobic descriptors in positive side indicating the need of bulky groups, steric and electronegative descriptors in negative coordinates hints with contribution by the electronegative substitutions as favourable and desirable moieties for enhancing the activity. The q(2), q(2)_se and Pred_r(2)se were found to be 0.5000, 0.6404 and 1.0094 respectively. A pharmacophore model was generated which suggested for necessity of aromatic, aliphatic carbon centre and hydrogen bond donor for development of newer DprE1 selective inhibitors.

A mononuclear bis-chelate complex of manganese(III) with 1,10-phenanthroline. Crystal and molecular structure of [Mn(phen)2Cl2]NO3·2.5CH3COOH

Abstract The title complex was synthesized by oxidizing manganese(II) with (NH4)2Ce(NO3)6 in acetic acid in the presence of the ligand. The structure of the complex was determined by X-ray crystallography. The nitrate ion and acetic acid molecules are severely disordered. The cis-MnN4Cl2 coordination sphere is Jahn—Teller distorted the axial MnN(2)(2.231 A) bond being longer than the equatorial MnN(1)(2.073 A) bond. Structural comparison are made with the analogous manganese(II) complex Mn(bpy)2Cl2. The observed optical and EPR spectra show that the complex undergoes disproportionation in various solvents giving manganese (III, IV) species.

Synthesis and structural characterization of an unsymmetrical (μ-OXO)-DI-(μ-ACETATO) manganese(III,III) complex ([Mn2O(OAc)2(H2O)(NO3)(bpy)2](ClO4)·CH3COOH)

Abstract The Ce4+ oxidation of Mn2+ in acetic acid in the presence of 2,2′-bipyridine gives the unsymmetrical complex [Mn2O(OAc)2(H2O)(NO3)(bpy)2](ClO4)·CH3COOH. The crystal structure of the complex shows the coordination of both nitrate and water to the metal ion. Each metal centre exhibits Jahn-Teller distortion and results in two types of MnOOAc bonds. The formation of different high-valent manganese complexes by Ce4+ oxidation under different conditions is discussed in the light of possible disproportionation and proton-coupled electron transfer reactions. The mode of (pseudo) Jahn-Teller distortion seen in manganese(III,III) complexes having the Mn2O(OAc)22+ core is reviewed.

Mononuclear manganese(III) aquo complexes. Crystal and molecular structures of [Mn(phen)(OH2)Cl3] and [Mn(acac)2-(OH2)2]ClO4·2H2O (acacH = acetylacetone, phen = 1,10-phenanthroline)

SummaryThe crystal and molecular structures of [Mn(phen)-(OH2)Cl3] (1) and [Mn(acac)2(OH2)2]ClO4·2H2O (2) were determined. A comparison is made of the Jahn-Teller distortion in these compounds with those observed in other manganese(III) complexes with monodentate axial ligands.

Influence of intermolecular interactions on coordination geometry-crystal and molecular structure of Ag(dmp)NO3· 2H2O (dmp = 2,9-DIMETHYL-1,10-PHENANTHROLINE)

Abstract Non-bonded interactions stabilise a normal Ag(dmp)NO3 molecule and a highly distorted [Ag2(dmp)2NO3]+ in the crystal of Ag(dmp)NO3 · 2H2O. The structure consists of two complex molecules, a mononuclear Ag(dmp)NO3 and NO3 bridged dinuclear cation [Ag2(dmp)2NO3]+ . The coordination around Ag in Ag(dmp)NO3 is of a regular 3+1 type while the dinuclear cation has a highly distorted geometry. The ring-ring stacking, CH3-CH3 interactions and C-H · O H-bonding stabilise the two complex molecules.

Design, synthesis and pharmacological evaluation of pyrimidobenzothiazole-3-carboxylate derivatives as selective L-type calcium channel blockers.

L-type voltage gated calcium channels play essential role in contraction of various skeletal and vascular smooth muscles, thereby plays important role in regulating blood pressure. Dihydropyridine receptors have been targeted for development of newer antihypertensive agents, one of the structurally analogs nucleus dihydropyrimidines have been reported earlier by us as a potential agent toward development of calcium channel modulator. A pre-synthetic QSAR was run and on the basis of structure activity relationship a series of twenty three molecules was synthesized and studied by myosin light chain kinase assay (MLCK), Angiotensin Converting Enzyme (ACE) colorimetric assay, non-invasive blood pressure (NIBP) and invasive blood pressure (IBP) methods. Molecules with significant efficacy were studied for their single crystal X-ray diffraction, molecular docking, molecular dynamics and post-synthetic QSAR. The NIBP and IBP methods screened molecules with better percentage inhibition versus time compared to standard drug Nifedipine. The lead compound ethyl 2-methyl-4-(3-nitrophenyl)-4H-pyrimido [2,1-b] [1,3] benzothiazole-3-carboxylate (26) presented a triclinic structure with polymeric chain packing in lattice. 26 exhibited IC50 on MLCK assay of 2.1±1.7 μM with selectivity of L-type calcium channels and comparative to Nifedipine. It offered satisfactory physicochemical properties with partition coefficient of (ClogP) 4.64. Its pharmacokinetic profile is also good with Cmax at 0.40 μg/ml by oral route with Tmax reaching in 0.5 h which means in 30 min. 26 also exhibits superior t1/2 of 5.4 h and oral bioavailability of (F) 56.75% with an AUC0-∞ of 0.84 μg h/ml. Molecular docking studies indicates toward the interaction of lead compound via hydrogen bonds with Lys144, Glu181 and Asp183, it forms the Van der Walls interactions with Ser18, Asp20, Asn187, Pro185, Glu180, Glu181 and Arg10 with Glide score and Glide energy to be -3.602 and -47.098, respectively. Post-synthetic QSAR of newly synthesized molecules indicates toward improvement with respect to steric descriptor which contributed negatively in former series.

Structure of [2-(aminomethyl)pyridine]silver(I) nitrate and EPR studies of its oxidation product

Abstract Reaction of AgNO3 with excess 2-(aminomethyl)pyridine (amp) in water led to the crystallization of Ag(amp)NO3 (1). Nearly linear coordination of silver (I) by pyyridine-N and amino-N from two different amp molecules results in a polymeric chain structure of 1. The packing is stabilized by ring-ring stacking interactions between two inversion-related polymer chains. Oxidation of 1 with (NH4)2S2O8 resulted in an orange solution from which a magnetically dilute AgII complex was crystallized by the addition of NH4PF6. It gave a well-resolved EPR spectrum and is formulated as silver(II) picolinate co-crystallized with NH4PF6.

Crystal and molecular structure of nitrato(6,6′-dimethyl-2,2′-bipyridine)silver(I). A dimer held by stacking and silver-silver interactions

SummaryThe crystal and molecular structure of Ag(dmbp)NO3, where dmbp=6,6′-dimethyl-2,2′-bipyridine, has been determined. The crystal consists of dimers formed by two symmetry-related molecules. Each dimeric unit is held together by (weak) Ag−Ag and heteroaromatic ring stacking interactions. Stacking interactions lead to a slipped stack arrangement of the dimers. The coordination around silver is very nearly planar (tetrahedral distortion angle=15°), with the nitrate ion acting as an unsymmetrical chelating ligand.

Synthesis, Characterization, and Crystal Structures of [Cu(phen)2Cl]Cl. 6.5H2O and [Cu(phen)2Br]Br

Two mixed-ligand complexes of copper(II) with 1,10-phenanthroline and halides [Cu(phen)2Cl]Cl.6.5H2O (1) and [Cu(phen)2 Br]Br (2), have been synthesized and characterized by microanalysis, spectroscopic, magnetic and single-crystal X-ray diffraction studies. The two complexes are isostructural in which the coordination geometry about the copper(II) ion is that of a trigonal bipyramid, with the central copper atom bound to one chloride (I) and one bromide (2) atom and four nitrogen atoms of the two phenanthroline ligands. The result of IR, electronic spectra, electron spin resonance (ESR) and magnetic measurements are discussed.