Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link between Enzyme Superfamilies

Mandelate racemase (MR), a member of the enolase superfamily, catalyzes the Mg2+-dependent interconversion of the enantiomers of mandelate. Several α-keto acids are modest competitive inhibitors of MR [e.g., mesoxalate (Ki = 1.8 ± 0.3 mM) and 3-fluoropyruvate (Ki = 1.3 ± 0.1 mM)], but, surprisingly, 3-hydroxypyruvate (3-HP) is an irreversible, time-dependent inhibitor (kinact/KI = 83 ± 8 M–1 s–1). Protection from inactivation by the competitive inhibitor benzohydroxamate, trypsinolysis and electrospray ionization tandem mass spectrometry analyses, and X-ray crystallographic studies reveal that 3-HP undergoes Schiff-base formation with Lys 166 at the active site, followed by formation of an aldehyde/enol(ate) adduct. Such a reaction is unprecedented in the enolase superfamily and may be a relic of an activity possessed by a promiscuous progenitor enzyme. The ability of MR to form and deprotonate a Schiff-base intermediate furnishes a previously unrecognized mechanistic link to other α/β-barrel enzymes utilizing Schiff-base chemistry and is in accord with the sequence- and structure-based hypothesis that members of the metal-dependent enolase superfamily and the Schiff-base-forming N-acetylneuraminate lyase superfamily and aldolases share a common ancestor

Use of metal catalysts bearing Schiff base macrocycles for the ring opening polymerization (ROP) of cyclic esters

© 2017 by the authors. Schiff base macrocycles are emerging as useful scaffolds for binding two or more catalytic metals in close proximity. Such coordination chemistry allows for the evaluation of potentially beneficial catalytic cooperative effects. In the field of ring opening polymerization (ROP) of cyclic esters, only a handful of metal systems bound by Schiff base [2 + 2] type macrocycles have been studied. Nevertheless, results to date have, for certain metals, identified some interesting structure activity relationships, whilst for other systems results have revealed particular combinations of metals and macrocycles to be virtually inactive. This perspective review takes a look at two types of recently-reported Schiff base macrocycles that have been employed as pro-ligands in the metal-catalyzed ROP of cyclic esters, specifically ε-caprolactone and rac-lactide

Atomistic Insight into the Role of Threonine 127 in the Functional Mechanism of Channelrhodopsin-2

Channelrhodopsins (ChRs) belong to the unique class of light-gated ion channels. The structure of channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2) has been resolved, but the mechanistic link between light-induced isomerization of the chromophore retinal and channel gating remains elusive. Replacements of residues C128 and D156 (DC gate) resulted in drastic effects in channel closure. T127 is localized close to the retinal Schiff base and links the DC gate to the Schiff base. The homologous residue in bacteriorhodopsin (T89) has been shown to be crucial for the visible absorption maximum and dark–light adaptation, suggesting an interaction with the retinylidene chromophore, but the replacement had little effect on photocycle kinetics and proton pumping activity. Here, we show that the T127A and T127S variants of CrChR2 leave the visible absorption maximum unaffected. We inferred from hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and resonance Raman spectroscopy that the hydroxylic side chain of T127 is hydrogen-bonded to E123 and the latter is hydrogen-bonded to the retinal Schiff base. The C=N–H vibration of the Schiff base in the T127A variant was 1674 cm−1, the highest among all rhodopsins reported to date. We also found heterogeneity in the Schiff base ground state vibrational properties due to different rotamer conformations of E123. The photoreaction of T127A is characterized by a long-lived P2380 state during which the Schiff base is deprotonated. The conservative replacement of T127S hardly affected the photocycle kinetics. Thus, we inferred that the hydroxyl group at position 127 is part of the proton transfer pathway from D156 to the Schiff base during rise of the P3530 intermediate. This finding provides molecular reasons for the evolutionary conservation of the chemically homologous residues threonine, serine, and cysteine at this position in all channelrhodopsins known so far

Mononuclear Cu(II) complexes of novel salicylidene Schiff bases: synthesis and mesogenic properties

Two new Schiff base ligands 1 and 2 (where 1 = 4-(2-hydroxybenzilidenamino)-phenyl-4-(decyloxy)-2-(pent-4-enyloxy)benzoate, 2 = 4-(4-(decyloxy)-2-hydroxybenziliden amino)-phenyl-4-(decyloxy)-2-(pent-4-enyloxy)benzoate) and their copper (Cu)(II) complexes have been synthesised and characterised. The derivatives were fully characterised structurally, and their mesomorphic behaviour was investigated by polarised optical microscopyand differential scanning calorimetry. The structure of Cu(II) complex having 1 as ligand (3) was determined by X-ray diffraction. The Schiff base ligands exhibit enantiotropic nematic phases, the Cu(II) complex 4 shows monotropic nematic phase behaviour, while compound 3 does not show mesomorphism

Concentration dependent tautomerism in green [Cu(HL1)(L2)] and brown [Cu(L1)(HL2)] with H2L1 = (E)-N’-(2-hydroxy-3-methoxybenzylidene)- benzoylhydrazone and HL2 = pyridine-4-carboxylic (isonicotinic) acid

The in situ formed hydrazone Schiff base ligand (E)-N’-(2-hydroxy-3-methoxybenzylidene)-benzoylhydrazone (H2L1) reacts with copper(II) acetate in ethanol in the presence of pyridine-4-carboxylic acid (isonicotinic acid, HL2) to green-[Cu(HL1)(L2)]・H2O・C2H5OH (1) and brown-[Cu(L1)(HL2)] (2) complexes which crystallize as concomitant tautomers where either the mono-anion (HL1)- or di-anion (L1)2- of the Schiff base and simultaneously the pyridine-carboxylate (L2)- or the acid (HL2) (both through the pyridine nitrogen atom) function as ligands. The square-planar molecular copper(II) complexes differ in only a localized proton position either on the amide nitrogen of the hydrazone Schiff base in 1 or on the carboxyl group of the isonicotin ligand in 2. The proportion of the tautomeric forms in the crystalline solid-state can be controlled over a wide range from 1:2 = 95 : 5 to ~2 : 98 by increasing the solution concentration. UV/Vis spectral studies show both tautomers to be kinetically stable (inert), that is, with no apparent tautomerization, in acetonitrile solution. The UB3LYP/6-31+G* level optimized structures of the two complexes are in close agreement with experimental findings. The solid-state structures feature 1D hydrogen-bonded chain from charge-assisted O(-) … H–N and O–H … (-)N hydrogen bonding in 1 and 2, respectively. In 1 pyridine-4-carboxylate also assumes a metal-bridging action by coordinating a weakly bound carboxylate group as a fifth ligand to a Cu axial site. Neighboring chains in 1 and 2 are connected by strong π-stacking interactions involving also the five- and six-membered, presumably metalloaromatic Cu-chelate rings

Polymeric Schiff bases. 17 - Azomethine copolymers

Chemical synthesis of azomethine copolymers by melt polymerization techniques - polymeric Schiff base

Synthesis, characterisation and biological activities of 2-Methylbenzyl 2-(dipyridin-2-yl methylene) hydrazinecarbodithioate.

A new tridentate nitrogen–sulphur Schiff base has been synthesised from the condensation of di-2-pyridylketone and a novel dithiocarbazate, S-2-methylbenzyl-dithiocarbazate (S2MBDTC). The Schiff base was characterized using various physico-chemical and spectroscopic techniques. The X-ray crystallographic analysis of the Schiff base is reported. The Schiff base crystallized in a monoclinic system with a space group of P 21/n, with crystal cell parameters a = 10.8128 (2) Å, b = 9.3832 (2) Å, c = 18.0352 (4) Å, β = 97.1311 (9)°. The Schiff base was found to be inactive against selected microbes and two breast cancer cell lines (MCF-7 = Human breast cancer cell line with positive estrogen receptor and MDA-MB-231 = Human breast cancer cell line with negative estrogen receptor)

(E,E)-N1,N2-Bis(2,6-di­fluoro­benzyl­idene)ethane-1,2-di­amine.

The asymmetric unit of the title compound, C16H12F4N2, comprises half of the potentially bidentate Schiff base ligand, with an inversion centre located at the mid-point of the central C—C bond. The crystal packing is stabilized by inter­molecular C—H⋯N and π–π inter­actions [centroid–centroid distance = 3.6793 (12) Å and inter­planar spacing = 3.4999 (7) Å]

Near-Infrared (NIR) Luminescent Homoleptic Lanthanide Salen Complexes Ln(4)(Salen)(4) (Ln = Nd, Yb Or Er)

The series of homoleptic tetranuclear [Ln(4)(L)(2)(HL)(2)(NO3)(2)(OH)(2)]center dot 2(NO3) (Ln = Nd, 1; Ln = Yb, 2; Ln = Er, 3; Ln = Gd, 4) have been self-assembled from the reaction of the Salen-type Schiff-base ligand H2L with Ln(NO3)(3)center dot 6H(2)O (Ln = Nd, Yb, Er or Gd), respectively (H2L: N, N'-bis(salicylidene) cyclohexane-1,2-diamine). The result of their photophysical properties shows that the strong and characteristic NIR luminescence for complexes 1 and 2 with emissive lifetimes in microsecond ranges are observed and the sensitization arises from the excited state (both (LC)-L-1 and (LC)-L-3) of the Salen-type Schiff-base ligand with the flexible linker.National Natural Science Foundation 21173165, 20871098Ministry of Education of China NCET-10-0936Higher Education of China 20116101110003State Key Laboratory of Structure Chemistry 20100014Education Committee Foundation of Shaanxi Province 11JK0588Hong Kong Research Grants Council, P. R. of China HKBU 202407, FRG/06-07/II-16)Hong Kong Research Grants Council, Robert A. Welch Foundation F-816Texas Higher Education Coordinating Board ARP 003658-0010-2006Petroleum Research Fund 47014-AC5Chemistr

Synthesis and Characterization of Enamine- And Schiff-Base Metal Complexes

Mentor: Dr. Colin CairnsEnamine- and Schiff-Base metal complexes have shown the potential to be catalysts in oxidation reduction reactions. To model these potential catalytic abilities, acetylacetone and 2-acetyldimedone were used to prepare enamine- and Schiff-Base metal complexes. Preliminary characterization of the ligands and metal complexes was carried out using infrared spectroscopy and cyclic voltammetry.Drake University, College of Arts & Science