Synthesis and structural studies of Rh, Pd, Ni complexes and one-pot synthesis of binuclear Ru complex [(η-p-cymene)Ru(μ2-Cl)3Ru{PhN(P(OC6H4OMe-o)2)2}Cl]

The Rh^I, Ru^II, Pd^I and Ni^II complexes of the aminobis(phosphonite), PhN(P(OC₆H₄OMe-o)₂)₂ (1) are reported. The reactions of 1 with [Rh(COD)Cl]₂ in 1:1 and 2:1 molar ratio afford the mono- and diolefin substituted chloro bridged chelate complexes, [(COD)Rh₂(μ₂-Cl)₂{PhN(P(OC₆H₄OMe-o)₂)₂}] (2) and [Rh(μ₂-Cl){PhN(P(OC₆H₄OMe-o)₂)₂}]₂ (3), respectively. Similarly, the cationic mono- and bis-chelate complexes, [Rh(COD){PhN(P(OC₆H₄OMe-o)₂)₂}]OTf (4) and [Rh{PhN(P(OC₆H₄OMe-o)₂)₂}₂]OTf (5) are obtained by treating 1 with [Rh(COD)Cl]₂ in the presence of AgOTf in appropriate ratios. The dinuclear Rh^I carbonyl complex, [RhCl(CO){μ-PhN(P(OC₆H₄OMe-o)₂)₂}]₂ (6) is prepared by treating 1 with 0.5 equiv. of [Rh(CO)₂Cl]₂. Reaction of 1 with cis-[NiBr₂(DME)] (DME = 1,2-dimethoxyethane) affords [{PhN(P(OC₆H₄OMe-o)₂)₂}NiBr₂] (7) whereas with [Ru-(η⁶-p-cymene)Cl₂]₂ in refluxing THF medium produces an interesting and rare bimetallic Ru^II complex, [(η⁶-p-cymene)Ru(μ₂-Cl)₃Ru{PhN(P(OC₆H₄OMe-o)₂)₂}Cl] (8). Redox condensation of the Pd⁰ and Pd^II derivatives with 1 affords the dinuclear Pd^I complex, [PdBr{μ-PhN(P(OC₆H₄OMe-o)₂)₂}]₂ (9). The formation and structure of complexes 2-9 are assigned through various spectroscopic and micro analysis data. The molecular structures of 5 and 7-9 are confirmed by single crystal X-ray diffraction studies.     

Crystal and Molecular Structure of Desmodin

The crystal structure of the title compound has been determined from X‐ray diffraction. The compound crystallizes from benzene in the orthorhombic system, space group P2₁2₁2₁, with unit cell parameters: a = 8.485(2), b = 9.816(2), c = 22.597(4) Å, Z = 4, V = 1881.9(7) ų. The structure was determined by direct methods and refined to a final R‐factor of 0.04. Six membered rings B and E are planar. Ring A and ring C are in slightly distorted sofa conformation. Ring D is in envelope conformation. The structure is stabilised by weak intermolecular C‐H...O hydrogen bonds.     

Phosphine free diamino-diol based palladium catalysts and their application in Suzuki-Miyaura cross-coupling reactions

Inexpensive air and moisture stable diamino-diol ligands [(2-OH-C₁₀H₆)CH₂(μ-NC₄H₈N)CH₂(C₁₀H₆-2-OH)] (1) and [(5-^tBuC₆H₃-2-OH)CH₂(μ-NC₄H₈N)CH₂(5-^tBuC₆H₃-2-OH)] (2) were synthesized by reacting corresponding alcohols with formaldehyde and piperazine. Treatment of ligands 1 and 2 with Pd(OAc)₂ in 1:1 molar ratio afforded neutral palladium complexes [Pd{(OC₁₀H₆)CH₂(μ-NC₄H₈N)CH₂(C₁₀H₆O)}] (3) and [Pd{(5-^tBuC₆H₃-2-O)CH₂(μ-NC₄H₈N)CH₂(5-^tBuC₆H₃-2-O)}] (4) in good yield. The palladium complexes 3 and 4 are employed in Suzuki-Miyaura cross-coupling reactions between phenylboronic acid and several aryl chlorides or bromides. They are found to be competent homogeneous catalysts for a variety of substrates to afford the coupled products in good to excellent yields. The crystal structures of compounds 2 and 4 are also reported.     

Synthesis of neutral (Pd(II), Pt(II)), cationic (Pd(II)), and water-induced anionic (Pd(II)) complexes containing new mesocyclic thioether-aminophosphonite ligands and their application in the Suzuki cross-coupling reaction

Mesocyclic thioether-aminophosphonite ligands, {-OC10H6(mu-S)C10H6O-}PNC4H8O (2a, 4-(dinaphtho[2,1-d:1',2'-g][1,3,6,2]dioxathiaphosphocin-4-yl)morpholine) and {-OC10H6(mu-S)C10H6O-}PNC4H8NCH3 (2b, 1-(dinaphtho[2,1-d:1',2'-g][1,3,6,2]dioxathiaphosphocin-4-yl)-4-methylpiperazine) are obtained by reacting {-OC10H6(mu-S)C10H6O-}PCl (1) with corresponding nucleophiles. The ligands 2a and 2b react with (PhCN)2PdCl2 or M(COD)Cl2 (M = Pd(II) or Pt(II)) to afford P-coordinated cis-complexes, [{(-OC10H6(mu-S)C10H6O-)PNC4H8X-kappaP}2MCl2] (3a, M = Pd(II), X = O; 3b, M = Pd(II), X = NMe; 4a, M = Pt(II), X = O; 4b, M = Pt(II), X = NMe). Compounds 2a and 2b, upon treatment with [Pd(eta3-C3H5)Cl]2 in the presence of AgOTf, produce the P,S-chelated cationic complexes, [{(-OC10H6(mu-S)C10H6O-)PNC4H8X-kappaP,kappaS}Pd(eta3-C3H5)](CF3SO3) (5a, X = O and 5b, X = NMe). Treatment of 2a and 2b with (PhCN)2PdCl2 in the presence of trace amount of H2O affords P,S-chelated anionic complexes, [{(-OC10H6(mu-S)C10H6O-)P(O)-kappaP,kappaS}PdCl2](H2NC4H8X) (6a, X = O and 6b, X = NMe), via P-N bond cleavage. The crystal structures of compounds 1, 2a, 2b, 4a, and 6a are reported. Compound 6a is a rare example of crystallographically characterized anionic transition metal complex containing a thioether-phosphonate ligand. Most of these palladium complexes proved to be very active catalysts for the Suzuki-Miyaura reaction with excellent turnover number ((TON), up to 9.2 x 10(4) using complex 6a as a catalyst).     

Modeling the interface between islet amyloid polypeptide and insulin-based aggregation inhibitors: correlation to aggregation kinetics and membrane damage

Human islet amyloid polypeptide (hIAPP) forms cytotoxic fibrils in type-2 diabetes and insulin is known to inhibit formation of these aggregates. In this study, a series of insulin-based inhibitors were synthesized and assessed for their ability to slow aggregation and impact hIAPP-induced membrane damage. Computational studies were employed to examine the underlying mechanism of inhibition. Overall, all compounds were able to slow aggregation at sufficiently high concentrations (10× molar excess); however, only two peptides showed any inhibitory capability at the 1:1 molar ratio (EALYLV and VEALYLV). The results of density functional calculations suggest this is due to the strength of a salt bridge formed with the Arg11 side chain of hIAPP and the inhibitors' ability to span from the Arg11 to past the Phe15 residue of hIAPP, blocking one of the principal amyloidogenic regions of the molecule. Unexpectedly, slowing fibrillogenesis actually increased damage to lipid membranes, suggesting that the aggregation process itself, rather than the fibrilized peptide, may be the cause of cytotoxicity in vivo.     

Triclabendazole: An Intriguing Case of Co‐existence of Conformational and Tautomeric Polymorphism

The crystal polymorphism of the anthelmintic drug, triclabendazole ( TCB ), is described. Two anhydrates (Forms I and II), three solvates, and an amorphous form have been previously mentioned. This study reports the crystal structures of Forms I ( 1 ) and II ( 2 ). These structures illustrate the uncommon phenomenon of tautomeric polymorphism. TCB exists as two tautomers A and B. Form I (Z′=2) is composed of two molecules of tautomer A while Form II (Z′=1) contains a 1:1 mixture of A and B. The polymorphs are also characterized by using other solid‐state techniques (differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), PXRD, FT‐IR, and NMR spectroscopy). Form I is the higher melting form (m.p.: 177 °C, ΔH_f=≈105±4 J g^?1) and is the more stable form at room temperature. Form II is the lower melting polymorph (m.p.: 166 °C, ΔH_f=≈86±3 J g^?1) and shows high kinetic stability on storage in comparison to the amorphous form but it transforms readily into Form I in a solution‐mediated process. Crystal structure analysis of co‐crystals 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 further confirms the existence of tautomeric polymorphism in TCB . In 3 and 11 , tautomer A is present whereas in 4 , 5 , 6 , 7 , 8 , 9 , 10 the TCB molecule exists wholly as tautomer B. The DFT calculations suggest that the optimized tautomers A and B have nearly the same energies. Single point energy calculations reveal that tautomer A (in Form I) exists in two low‐energy conformations, whereas in Form II both tautomers A and B exist in an unfavorable high‐energy conformation, stabilized by a five‐point dimer synthon. The structural and thermodynamic features of 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 are discussed in detail. Triclabendazole is an intriguing case in which tautomeric and conformational variations co‐exist in the polymorphs.     

A one-pot catalysis: the strategic classification with some recent examples

In this "Emerging Area", the strategic classification of one-pot catalysis, i.e. cooperative, relay and sequential catalysis, is described. In order to illustrate this classification, we take the readers through a series of recent examples which utilize either metal-metal, metal-organo and organo-organo catalysts. The compilation clearly demonstrates the explosive growth and power of this field, which has become, in the last few years, an important technique particularly in the case of enantioselective catalysis.     

A meglumine catalyst–based synthesis,molecular docking,and antioxidant studies of dihydropyrano[3, 2-b]chromenedione derivatives

A simple method was employed for the synthesis of dihydropyrano[3, 2-b]chromenedione derivatives ( 4a-o) in high yields by condensation of 5, 5-dimethylcyclohexane-1, 3-dione( 1 ), different aromatic aldehydes ( 2a-o ), and 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one( 3 ), using meglumine as a stable and reusable catalyst. Meglumine, an amino sugar, was employed as an environmentally benign catalyst, due to its splendid properties such as being inexpensive, recyclable, and biodegradable. The accomplished protocol employs low catalyst loading and easy work-up for the synthesis of 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one derivatives. A great asset is that without any significant loss, the catalyst could be recovered and reused for extended synthetic steps. This offer huge advantage to overcome recyclability issues. Our synthesized compounds were analyzed by IR, ¹H, ¹³C NMR, mass spectra and evaluated for their antioxidant properties by 1, 1-diphenyl-2-picryl hydrazyl radical (DPPH), hydrogen peroxide(H₂O₂), and nitric oxide (NO) scavenging methods. The correlation in exhibition of antioxidant activity was effective at all doses. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein; 4k exhibited marked binding affinity with excellent docking score of −7.6 Kcal/mol and emerged as a lead compound.