Binding Conformation of 2-Oxoamide Inhibitors to Group IVA Cytosolic Phospholipase A2 Determined by Molecular Docking Combined with Molecular Dynamics

The group IVA cytosolic phospholipase A2 (GIVA cPLA2) plays a central role in inflammation. Long chain 2-oxoamides constitute a class of potent GIVA cPLA2 inhibitors that exhibit potent in vivo anti-inflammatory and analgesic activity. We have now gained insight into the binding of 2-oxoamide inhibitors in the GIVA cPLA2 active site through a combination of molecular docking calculations and molecular dynamics simulations. Recently, the location of the 2-oxoamide inhibitor AX007 within the active site of the GIVA cPLA2 was determined using a combination of deuterium exchange mass spectrometry followed by molecular dynamics simulations. After the optimization of the AX007-GIVA cPLA2 complex using the docking algorithm Surflex-Dock, a series of additional 2-oxoamide inhibitors have been docked in the enzyme active site. The calculated binding affinity presents a good statistical correlation with the experimental inhibitory activity (r 2 = 0.76, N = 11). A molecular dynamics simulation of the docking complex of the most active compound has revealed persistent interactions of the inhibitor with the enzyme active site and proves the stability of the docking complex and the validity of the binding suggested by the docking calculations. The combination of molecular docking calculations and molecular dynamics simulations is useful in defining the binding of small-molecule inhibitors and provides a valuable tool for the design of new compounds with improved inhibitory activity against GIVA cPLA2

Copper(I)/(II) or silver(I) ions towards 2-mercaptopyrimidine: An exploration of a chemical variability with possible biological implication

Direct reaction of copper(I) chloride with 2-mercaptopyrimidine (pmtH) in the presence of the triphenylphosphine (tpp) in 1:1:2 M ratio forms the mixed ligand Cu(I) complex with formula [CuCl(tpp)2(pmtH)] (1). The dimeric {[Cu(tpp)(pmt)]2 0.5(MeOH)} (2) complex was derived from the reaction of 1 with twofold molar amount of sodium hydroxide. However, the reaction of copper(II) sulfate or nitrate with pmtH and tpp in 1:2:2 M ratio, unexpectedly results in the formation of the [CuSH(tpp)2(pmtH)] (3) complex. Further studies have shown that the [Cu(tpp)2(pmt)] (4) complex is formed by reacting copper(II) acetate with pmtH in the presence of tpp in 1:2:2 M ratio, while in the absent of tpp, the Cu(CH3COO)2 or CuSO4 is found to oxidizes pmtH to its corresponding disulfide (pmt)2. For comparison the mixed ligand silver(I) chloride or nitrate complexes with formula [AgCl(tpp)2(pmtH)] (5) or [Ag(NO3)(tpp)2(pmtH)] (6) are also synthesized by reacting of the AgCl or AgNO3 with pmtH and tpp in 1:2:2 M ratio. The complexes have been characterized by elemental analyses, m.p., vibrational spectroscopy (mid-, far-FT-IR and Raman), 1 H NMR, UV–Vis, ESI-MS, TG–DTA spectroscopic techniques and single crystal X-ray crystallography at ambient conditions. Photolysis of 1–6, was also studied and the results showed formation of triphenylphosphine oxide. The complexes 1–6, were used to study their influence upon the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX) experimentally and theoretically. The binding of 1–4 with LOX was also investigated by saturation transfer difference 1 H NMR experiments (STD

Oxalamide based coordination polymers

Employment of N,N′-bis(2-dicarboxyphenyl)-oxalamide (H4L) in the M2+ chemistry (M = Mg, Mn, Co, Ni, and Zn) afforded five 2-D coordination polymers and one 1-D coordination polymer. The crystal structures of all complexes have been determined by single-crystal X-ray crystallography. The five 2-D polymers with the general formula [M(H2L)(H2O)2] n (M = Mg 1, Mn 2, Co 3, Ni 4, Zn 6) are based on the di-anion of the oxalamide ligand (H2L2–) while the poorly diffracting complex 5, {[Ni2(L)(H2O)3]·(H2O)2} n, is based on the tetra-anion of the oxalamide ligand (L4–). The magnetic properties of 2–4 revealed weak antiferromagnetic interactions between the spin carriers. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Synthesis, experimental and theoretical investigation of a new type nickel dithiolene complex

A new nickel complex with an extended multisulfur dithiolene ligand, [Ni(dmeodddt)2] (dmeodddt = 5,6-dimethoxy-5,6-dihydro-1,4-dithiine-2, 3-dithiolate), has been synthesized and characterized by IR, Raman, UV-Vis and NMR spectroscopy. Its crystal structure has been determined by X-ray crystallography, showing that the Ni atom is tetra-coordinated and has a square planar geometry with the methoxy groups placed above and below the metal dithiolene core, due to stereochemical hindrance. Electrochemical measurements showed that the complex exhibits four 1e reversible redox waves. The results of theoretical calculations showed a good agreement with the experimental findings and gave answers about its electronic structure. © 2013 Elsevier Ltd. All rights reserved

New type dithiolene complex based on 4,5-(1,4-dioxane-2,3-diyldithio)-1,3-dithiol ligand: Synthesis, experimental and theoretical investigation

A new Nickel complex with an extended multisulfur dithiolene ligand Ni(edodddt)2 (edodddt = 2,3,4α,8α-tetrahydro-dithiine [2,3-b] [1,4] dioxo-6,7-dithiolene) has been synthesized and characterized by electrochemical measurements, IR, UV-Vis and NMR spectroscopy. Its crystal structure was resolved by X-ray diffraction on a single crystal. DFT calculations were made in order to compare the results with the experimental findings and gain an insight of the properties of this new dithiolene complex. © 2009 Elsevier Ltd. All rights reserved

Metallo-Ligand Based 3d/4f Coordination Polymers: Synthesis, Structure and Magnetic Properties

Employment of N,N′-bis(2-hydroxy-4-carboxyphenyl)oxalamide (H6L) in Cu2+ chemistry afforded the mononuclear complex (Et4N)4[CuL] ⋅ 13H2O (A) which comprises a square planar [CuL]4− complex with several O donor atoms in its periphery. The 1 : 1 reaction between complex A and Ln(NO3)3 ⋅ xH2O (Ln=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er and Yb, x=6 or 9) in 1 : 4 mixture of ethanol/water in the presence of excess of KCl yielded two families of isomorphous 3d/4f coordination polymers, namely (Et4N)0.5[K0.5(H2O)Ln(H2O)4(CuL)] ⋅ 3H2O [Ln=La(1), Ce(2), Pr(3), Nd(4), Sm(5), Eu(6) and Gd(7)] and [K(H2O)Ln(H2O)4(CuL)] ⋅ ⋅6H2O [Ln=Tb(8), Dy(9), Ho(10), Er(11) and Yb(12)]. The crystal structures of 2–4 revealed the presence of 3D coordination polymers while the crystal structure of 9 the presence of a 2D coordination polymer. In both 3d/4f families, complex A retains its original structure and serves as a “metallo-ligand”. The magnetic properties of 2–4, 7–9, 11 and 12 are discussed. © 2022 Wiley-VCH Gmb

A Microporous Co(II)-Based 3-D Metal Organic Framework Built from Magnetic Infinite Rod-Shaped Secondary Building Units

Invited for the cover of this issue is Anastasios Tasiopoulos from the University of Cyprus. The cover image shows photos from the southwestern Cyclades island group of the Aegean Sea, which contain a wealth of minerals and rocks. Some of these exhibit porous structures and interesting magnetic properties. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Synthesis and non-linear optical properties of some novel nickel derivatives

The synthesis of a new nickel complex with an extended multi-sulfur dithiolene ligand Ni(etodddt)2 (etodddt = 4,5-(1,4-oxathiane-2,3- diyldithio)-1,3-dithiole) is described. It is characterized analytically and spectroscopically. The structure of the compound is determined by single crystal X-ray crystallography. Its redox potentials are determined using cyclic voltammetry and are compared with similar dithiolene complexes. Several other nickel derivatives are synthesized: bis(5,6-dihydro-1,4-dithiine-2,3-dithiole) nickel (Ni(dddt)2) and bis(6,7-dihydro-5H-[1,4] dithiepine-2,3- ddithiole) nickel (Ni(pddt)2). The non-linear optical response of the synthesized dithiolenes is measured in the visible (532 nm) and in the infrared (1064 nm) using the Z-scan technique with picosecond laser pulses. Both the refractive and absorptive parts of the third-order susceptibility χ(3) are determined and the second-order hyperpolarizabilities γ of the dithiolenes are determined and compared between them and with other reported in the literature data. The second hyperpolarizabilities of the synthesized metal derivatives are calculated by employing a series of computational approaches, involving density functional theory and a semi-empirical method. The first strong transition of the derivatives is attributed mainly to HOMO-LUMO pair connected with the intramolecular charge transfer π → π. Similar trends are observed between the experimental and the theoretical second hyperpolarizabilities, although the former are much larger due to resonance enhancement. The reported analysis demonstrates the complementarity of both experimental and theoretical results. It is shown that modest substitution of Ni(SCH)4, for example substitution of four H atoms by two S2C2H4 groups, leads to a very large increase of the second hyperpolarizability. © 2010 Elsevier B.V. All rights reserved