Succinate Ligand Research Articles

Progress Toward Understanding Protein Control of Reaction Outcome in the Diverse Reactivity of Iron(II)‐ and 2‐Oxoglutarate‐dependent Oxygenases

In mammals, iron(II)‐ and 2‐oxoglutarate‐dependent (Fe/2OG) dioxygenases have roles in oxygen and body‐mass homeostasis, connective tissue synthesis, and control of transcription and epigenetic inheritance.1 Related enzymes in plants, fungi, and bacteria enable diverse biosynthetic pathways to valuable natural‐product drugs by catalyzing halogenation, epimerization, desaturation, cyclization, ring‐opening/expansion, and endoperoxidation reactions; some of these enzymes even catalyze multiple reaction types within the same pathway!2 Almost every enzyme in this class initiates its reaction by using a common oxoiron(IV) (ferryl) intermediate, first demonstrated by the Penn State group in 2003,3,4 to abstract a hydrogen atom from its target substrate (Figure 1). The iron(II)‐chelating co‐substrate, 2OG, is oxidatively decarboxylated to a succinate ligand in formation of the ferryl complex. To mediate an outcome other than hydroxylation, an enzyme must avoid what can be a facile “oxygen rebound,” Groves term for the coupling of the substrate radical with the iron‐coordinated oxygen just after it abstracts the hydrogen. By direct biophysical observation and “metallomimicry” of intermediates, we have rationalized several of these outcomes in terms of the alternative fates of the substrate radical and the structural features of the enzyme that avert oxygen rebound to enable these alternative fates.5‐11 Very recently, we explained how the most unusual Fe/2OG oxygenase discovered to date, the microbial ethylene‐forming enzyme (EFE), branches from the canonical pathway even before the ferryl intermediate is formed (Figure 2),12,13 leading to global fragmentation of 2OG to three carbon dioxide equivalents and ethylene, a reaction that requires but does not transform the amino acid L‐arginine. The elucidation of the unusual “radical‐polar‐crossover” mechanism of EFE13 significantly expands the paradigm of 2OG‐assisted dioxygen activation pathways and suggests unexpected uses of EFE in biotechnology.1. Hausinger, R. P. Crit. Rev. Biochem. Mol. Biol., 2004, 39, 21–68.2. Bollinger, J. M., Jr., et al. 2015 in RSC Metallobiology Series No. 3. R.P. Hausinger and C.J. Schofield, eds. pp. 95‐122. Royal Society of Chemistry, Washington, D.C.3. Price, J. C., et al. Biochemistry,2003,42,7497‐7508.4. Price, J. C., et al. J. Am. Chem. Soc., 2003, 125, 13008‐13009.5. Matthews, M. L., et al. Proc. Natl. Acad. Sci. USA, 2009, 106, 17723‐17728.6. Chang, W.‐c., et al. Science 2014, 343, 1140‐1143.7. Martinie, R. J., et. al. J. Am. Chem. Soc. 2015,137, 6912‐6919.8. Martinie, R. J., et al. Inorg. Chem. 2017, 56, 13382‐13389.9. Dunham, N. P. et al. J. Am. Chem. Soc. 2018, 140, 7116‐7128.10. Dunham N. P., et al. J. Am. Chem. Soc. 2019, 141, 9964‐9979.11. Pan, J., et al. J. Am. Chem. Soc.2019, 141, 15153−15165.12. Copeland, R. A., et al. J. Am. Chem. Soc. 2021, 143, 2293‐2303.13. Copeland, R. A., et al. Science2021, 373, 1489‐1493.

Impact of flexible succinate connectors on the formation of tetrasulfonylcalix[4]arene based nano-sized polynuclear cages: structural diversity and induced chirality study

The formation of three types of supramolecular coordination cages is described. Tetrasulfonylcalixarene, combined with metallic salts (Ni, Co and Zn) and the flexible succinate ligand, led to cages. H bonded induced chirality was observed for both isomorphous cages.

Molecular docking and simulation of IcaC protein as O-succinyltransferase function in staphylococcus epidermidis biofilm formation.

Intercellular adhesion (IcaADBC) operon is necessary for PNAG (Polyβ-1,6-N-acetyl-D-glucosamine) biosynthesis of biofilm formation in Staphylococcus epidermidis. IcaC protein has a wide range of functions in terms of growth phase variation, migration, transposon insertion, PNAG modification, biofilm formation. Unusual TTTA signature motifs were identified from nucleotide sequence. Asparagine-linked glycosylation consensus motifs were identified at position 169 and 240. S. epidermidis was a close evolutionary association with S. haemolyticus and other Staphylococcus spp. Due to the non-availability of crystal structure, protein threading procedure was selected for constructing a full length IcaC three-dimensional structure. QMEANBrane structure quality assessment with model scores −100000 range within predicted integral membrane structure. IcaC motif constitutes 18 transmembrane helix, 37 helix-helix interaction, 8 beta turn, 2 gamma turn. Binding free energy was calculated with their succinate ligand docking form hydrogen bond with critical amino acids showed ΔG score −2.574 ​kJ/mol using Schrödinger. Serine (Ser96), Glutamic acid (Glu99), Tryptophan (Trp191) were active site amino acids form the catalytic core required for O-succinyltransferase function. Molecular dynamics simulation (MDS) was performed to evaluate the stability of IcaC protein and IcaC-Succinate binding complexes with the active site amino acids throughout trajectories captured with time scale 100 ns simulation period using GROMACS 4.5.

Crystal structure and Hirshfeld surface analysis of one-dimensional copper(II) coordination polymer incorporating succinate and tetra-methyl-ethylene-diamine ligands.

The reaction of copper nitrate with succinic acid (succH) and N,N,N',N'-tetra-methyl-ethylenedi-amine (TMEDA) in basic solution produces the complex catena-poly[[[(N,N,N',N'-tetra-methyl-ethylenedi-amine-κ2 N,N')copper(II)]-μ-succinato-κ2 O 1:O 4] tetra-hydrate], {[Cu(C4H4O4)(C6H16N2)]·4H2O} n or {[Cu(succ)(tmeda)]·4H2O} n . Each carboxyl-ate group of the succinate ligand coordinates to a CuII atom in a monodentate fashion, giving rise to a distorted square-planar geometry. The succinate ligands bridge the CuII centres, forming one-dimensional polymeric chains. Hydrogen bonds between the ligands and water mol-ecules link these chains into sheets that lie parallel to the ac plane. Hirshfeld surface analysis, d norm and two-dimensional fingerprint plots were examined to verify the contributions of the different inter-molecular contacts within the supra-molecular structure.

Reviewing Rare Earth Succinate Frameworks from the Reticular Chemistry Point of View: Structures, Nets, Catalytic and Photoluminescence Applications

AbstractThe intense development that Metal‐Organic Frameworks have experienced along the last two decades, reflects the interest on these compounds as a new generation of multifunctional materials with diverse applications. The first works of Prof. Omar Yaghi devoted to obtain open frameworks by combining rigid aromatic linkers and a variety of metal centers, encouraged the creativity of the scientific community to designcoordination polymers employing aliphatic ligands as multitopic building blocks . Here, a revision of the literature dedicated to rare earth coordination networks mainly based in succinate ligand and derivatives is performed. A structural analysis of 2D and 3D frameworks based on rare earth elements and succinate, was carried out considering their inner connectivities and topologies with focus on those compounds with potential photoluminescent and catalytic technological applications. Thus, a variety of optical behaviours regarding the emission mechanisms, colours, lifetimes, quantum yields as well as chemical/thermal sensing properties are presented and compared with related phases found in literature. The catalytic performance of several rare earth‐succinates in three important reactions is discussed in terms of their acidity, dimensionality and available active centers towards the formation of the desired products analysing parameters such as selectivity, yields and TOFs.

A one-dimensional copper(II) coordination polymer incorporating succinate and N,N-diethylethylenediamine ligands: crystallographic analysis, vibrational and surface features, and DFT analysis.

Transition metal atoms can be bridged by aliphatic dicarboxylate ligands to produce chains, layers and frameworks. The reaction of copper sulfate with succinic acid (H2succ) and N,N-diethylethylenediamine (deed) in basic solution produces the complex catena-poly[[[(N,N-diethylethylenediamine-κ2N,N')copper(II)]-μ-succinato-κ2O1:O4] tetrahydrate], {[Cu(C4H4O4)(C6H16N2)]·4H2O}n or {[Cu(succ)(deed)]·4H2O}n. Each carboxylate group of the succinate ligand coordinates to a CuII atom in a monodentate fashion, giving rise to a square-planar coordination environment. The succinate ligands bridge the CuII centres to form one-dimensional polymeric chains. Hydrogen bonds between the ligands and water molecules link these chains into sheets that lie in the ab plane. Density functional theory (DFT) calculations were used to support the experimental data. From these calculations, a good linear correlation was observed between the experimental and theoretically predicted structural and spectroscopic parameters (R2 ∼ 0.97).

Pt(IV) prodrugs designed to bind non-covalently to human serum albumin for drug delivery.

Albumin is the most abundant protein in human serum and drugs that are administered intravenously inevitably interact with it. We present here a series of platinum(IV) prodrugs designed specifically to enhance interaction with human serum albumin (HSA) for drug delivery. This goal is achieved by asymmetrically functionalizing the axial ligands of the prodrug so as to mimic the overall features of a fatty acid. Systematic variation of the length of the aliphatic tail tunes the cellular uptake and, consequently, the cytotoxicity of cis,cis,trans-[Pt(NH3)2Cl2(O2CCH2CH2COOH)(OCONHR)], 4, where R is a linear alkyl group. Investigation of an analogue bearing a fluorophore conjugated to the succinate ligand confirmed that these compounds are reduced by biological reductants with loss of the axial ligands. Intracellular release of cisplatin from 4 was further confirmed by observing the characteristic effects of cisplatin on the cell cycle and morphology following treatment with the prodrug. The most potent member of series 4, for which R is a hexadecyl chain, interacts with HSA in a 1:1 stoichiometry to form the platinum-protein complex 7. The interaction is non-covalent and extraction with octanol completely removes the prodrug from an aqueous solution of HSA. Construct 7 is robust and can be isolated following fast protein liquid chromatography. The nature of the tight interaction was investigated computationally, and these studies suggest that the prodrug is buried below the surface of the protein. Consequently, complexation to HSA is able to reduce the rate of reduction of the prodrug by ascorbate. The lead compound from series 4 also exhibited significant stability in whole human blood, attributed to its interaction with HSA. This favorable redox profile, in conjunction with the established nonimmunogenicity, biocompatibility, and enhanced tumor accumulation of HSA, produces a system that holds significant therapeutic potential.

Effect of temperature on formation of two new lanthanide metal-organic frameworks: Synthesis, characterization and theoretical studies of Tm(III)-succinate

Two new metal-organic frameworks (MOFs) have been synthesized under different hydrothermal conditions and characterized by single-crystal X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and elemental analysis. Compound 1, crystallized in space group P1̄ with the formula [Tm2(L)3(H2O)2]·H2O, (H2L=succinic acid), has triclinic cell parameters of a=7.61780(10), b=10.58050(10), c=12.71030(10), α=95.3130(10), β=107.4370(10), γ=111.0960(10) and a cell volume of 888.446(16)Å3. Compound 2, crystallized in space group I2/a with the same formula, is monoclinic, with cell parameters of a=13.77020(10), b=7.63170(10), c=17.2410(2), β=101.303(10) and a cell volume of 1776.72(3)Å3. The results of this work indicate that a flexible succinate ligand that provides several modes of coordination can lead to different conformations, depending on the temperature used in the reaction. In the theoretical part of this study, semiempirical quantum chemistry methods using AM1, PM3 and PM6 models are employed to predict the structure of MOFs, calculate the geometric and crystallographic parameters, and make comparisons with experimental data.

Kinetics and mechanism of aquation of bromopentammine cobalt(III) cation assisted by ion-pairing succinate anion in ethane-2-diol-water mixtures

The aquation kinetics of bromopentammine cobalt(III) ion has been investigated in the presence of different concentrations of succinate ion in aqueous medium and that mixed with ethane-1,2-diol (up to 50%, w/w) within the temperature range (35-65 o C). The ion-pairing succinate ion concentration (L) and the observed rate constant have been determined at different experimental conditions. The thermodynamic parameters of activation have been calculated and discussed in terms of solvent effects. Also the extrathermodynamic analyses of the obtained results have been discussed on the basis of solute-solvent and solvent-solvent interactions. An empirical correlation between the rate coefficient and the concentration of the ion-pairing succinate ligand (L) has been established and a suggested reaction mechanism is proposed.

Succinate Receptors in the Kidney

The G protein-coupled succinate and α-ketoglutarate receptors are closely related to the family of P2Y purinoreceptors. Although the α-ketoglutarate receptor is almost exclusively expressed in the kidney, its function is unknown. In contrast, the succinate receptor, SUCRN1, is expressed in a variety of tissues, including blood cells, adipose tissue, liver, retina, and the kidney. Recent evidence suggests SUCRN1 and its succinate ligand are novel detectors of local stress, including ischemia, hypoxia, toxicity, and hyperglycemia. Local levels of succinate in the kidney also activate the renin-angiotensin system and together with SUCRN1 may play a key role in the development of hypertension and the complications of diabetes mellitus, metabolic disease, and liver damage. This makes the succinate receptor a promising drug target to counteract an expanding number of interrelated disorders.

Two-Dimensional Hydrogen-Bonded Polymer from Nickel(II) Tetraaza Macrocyclic Complex and Succinate Ligand

The reaction of [Ni(L)]Cl2·2H2O (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,01.18,07.12] docosane) with succinic acid (C4H6O4) yields a 2D hydrogen-bonded polymer with formula [Ni(L)(C4H5O4)2] (1). This polymer complex has been characterized by X-ray crystallography, spectroscopy and cyclic voltammetry. The complex has a center of symmetry. The crystal structure of 1 exhibits a distorted octahedral geometry about Ni atom with four nitrogen atoms of the macrocycle and two oxygen atoms of the succinate ligand at the trans position. Compound 1 crystallizes in the monoclinic system C2/c with a = 14.8203(11), b = 12.3070(8), c = 17.4164(12) A, β = 107.356(6)°, V = 3032.1(4) A3, Z = 4. Electronic spectrum of 1 reveals a high-spin octahedral environment. Cyclic voltammetry of 1 undergoes two waves of a one-electron transfer corresponding to NiII/NiIII and NiII/NiI processes. The reaction of [Ni(L)]Cl2·2H2O (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,01.18,07.12]docosane) with succinic acid (C4H6O4) yields a 2D hydrogen-bonded polymer with formula [Ni(L)(C4H5O4)2], which exhibits a high-spin nickel(II) ion in a O h environment with four nitrogen atoms of the macrocycle and two oxygen atoms of the succinate ligand at the trans position.

Synthesis and fluorescence of multi-dimensional structures of two cobalt (II) complexes between 2,2′-bipyridine and different chain length of aliphatic dicarboxylic, succinic or glutaric acid

Two coordination polymers [Co(μ-succinato)(H 2O) 2(2,2′-bipy)] 1 and [Co 2(μ-H 2O)(μ-glutarato) 2(2,2′-bipy) 2] 2 have been synthesized and characterized by single crystal X-ray diffraction, IR, thermal analysis (TGA) and fluorescence measurement. The crystallographic analysis reveals that these two compounds exhibit different in structures. Compound 1, cobalt (II) complex with succinic acid shows 1-D helical chain whereas compound 2, cobalt (II) complex with glutaric acid shows 1-D dinuclear polymeric chain. In compound 1, hydrogen bond are formed between water of crystalline, coordination water and uncoordinated carboxyl group of succinate ligand with adjacent chain extended 1-D chain into 2-D layer and also weak π– π interaction extend 2-D layer into 3-D network. Compound 2, π– π interaction between 2,2′-bipyridine in adjacent chain are formed resulting in 2-D layer. Each 2-D layer form Van der Waals interaction to each other building 3-D framework. In addition, these two compounds exhibit strong fluorescence at room temperature in the solid state.

Synthesis, characterization and crystal structure of copper(II) complex of succinate and 2,2′-bipyridyl

Abstract The mixed ligand copper(II) complex of succinate and 2,2′-bipyridyl was synthesized from disodium succinate, 2,2′-bipyridine and copper nitrate. The structure of the synthesized complex was determined by micro-analysis, IR, thermogravimetric analysis and X-ray crystallography. The thermal decomposition of the complex under an inert atmosphere has been studied. The crystal structure is monoclinic space group P21/n with parameters a = 15.080(9) A, b = 22.406(13) A, c = 15.138(9) A, β = 91.539°, V = 5113(5) A3, Z = 4, 1.534 Mg/m3, R = 0.0911 and Mr = 1181.08. The geometry around copper atom is distorted octahedral. The complex consists of a dimer in which each Cu atom is linked through two carboxylate–oxygen atoms from a tetradentate succinate ligand and four nitrogen atoms from two chelating 2,2′-bipyridyl groups. The succinate ligand bridges between the two Cu atoms.

Three-dimensional ionic frameworks built up from La (III) and Ce (III) succinates

Two three-dimensional ionic open-framework rare-earth succinates have been synthesized. The lanthanum-based compound, 1, was obtained by the silica gel technique and the cerium-based compound, 2, via grown phase under reflux. These two coordination polymers are isostructural. Their layer-type structure is built up from infinite chains of one-edge-sharing polyhedra, discrete chloride ions and lattice water molecules. Strong hydrogen bonds cross link the two-dimensional substructure into a three-dimensional open-framework exhibiting wide channels parallel to [1 0 0] direction. The tetratopic succinate ligand, involved in a syn–anti bridging-chelating mode, links the metal atoms through μ 2-oxo bridges. The thermal analysis confirms the high stability of the materials, probably due to the infinite metal–oxygen–metal arrays.

Poly[[tetraaquadi-μ4-succinato-μ5-succinato-diytterbium(III)] hexahydrate

The title compound, {[Yb2(C4H4O4)3(H2O)4]·6H2O}n, is a two-dimensional open-framework built up from centrosymmetric binuclear units developed along [100] through the spacers of four extended ligands, and inter­connected along [101] by two twisted ligands, forming a layered coordination polymer in the (010) plane embedding six uncoordinated water mol­ecules. The water-coordinated YbIII atom completes a nine-coordination mode via seven O atoms from four carboxyl­ate ligands, in a monocapped square anti­prism. One independent succinate ligand, located on an inversion center, is in a bidentate coordination mode, exhibiting an anti conformation. The second independent succinate ligand, in a gauche conformation, is bidentate and bridging–chelating, involving one triply ligating O atom displaying the longest Yb—O bond [2.598 (2) Å]. In addition to inter­layer hydrogen bonds, intra­layer hydrogen bonds involve, as acceptors, carboxyl­ate O atoms which are in bidentate mode.

Diamine Substitution Reactions of Tetrahydrate Succinato Nickel, Cobalt, and Zinc Coordination Polymers

Investigation on the substitution reactions of tetrahydrate succinato metal coordination polymers with diamine ligands results in the isolations of four new coordination polymers, [M(suc)(bpy)(H2O)2]n·nH2O (M = Ni, 2; M = Co, 2a), [Ni(suc)(phen)(H2O)]n (3), and [Zn(suc)(bpy)]n·2nH2O (4) (H2suc = succinic acid, bpy = 2,2‘-bipyridine, and phen = 1,10-phenanthroline). In the isomorphous compounds of 2 and 2a, the metal(II) ions are linked by a bridging succinate ligand to form 1D helix chains in bis-monodentate mode. In compounds 3 and 4, the succinate ligand connects adjacent nickel/zinc(II) atoms through three oxygen atoms from two carboxyl groups, forming an infinite zipper like chain along the a axis. The nickel compound 3 forms a double helix chain through strong hydrogen bonding. Notably, the double-stranded ribbons in compound 4 formed through moderately strong face-to-face π−π stacking segregated an unprecedented water chain constructed from dimeric water molecules.

Blue-greenish photoluminescent Gd(III) complexes with flexible succinate ligand

Two gadolinium complexes, [Gd 2L 3(H 2O) 2] n ( 1) and [Gd 2L 3(H 2O) 2] n · nH 2O ( 2) (L=succinate) have been hydrothermally synthesized. Complexes 1 and 2 crystallize in space group P-1 and C2/ c, respectively. The structure of 1 has a 3D open framework containing different channels, while the structure of 2 possesses a similar 3D framework but containing water guests within the channels. Succinate ligands in 1 and 2 adopt three and two conformations, respectively. Both complexes exhibit intense blue-greenish photoluminescence upon UV excitation in the solid state at room temperature.

The chemistry of fumarate and maleate inhibitors with platinum hydrosilylation catalysts

Pt(M viM vi) x (M viM vi = 1.3-divinyltetramethyl disiloxane), 1, was reacted with dimethyl fumarate to give 2. Compound 2 was investigated by 1H and 13C NMR spectroscopy which showed it to be a mono-nuclear platinum compound containing one dimethyl fumarate and one chelating M viM vi ligand. The reaction of 1 with dimethyl maleate gave 3 which was analogous in structure to the fumarate product as shown by 1H and 13C NMR spectroscopy and extended X-ray absorption fine structure spectroscopy (EXAFS). The EXAFS analysis showed the presence of Pt-C bonds and a through space close contact between Pt and the O from the carbonyl. The NMR assignments were confirmed by comparing the NMR spectra of 2 and 3 with that of (PPh 3)Pt(M viM vi), 4. Reaction of 2 or 3 with an excess of an SiH-containing compound (either MD HD HM (MD HD HM = 1,3-bis(trimethylsiloxy)-1,3-dimethylsiloxane) or Et 3SiH) gave 5 in all cases. Compound 5 contains an alkyl succinate ligand. Hydrogenation of the fumarate ligand (of 2) or of the maleate ligand (of 3) occurs by reaction with SiH; 5 appears to be an intermediate in the hydrogenation process. The reaction between 4, dimethylmaleate, and MD HD HM also gives dimethyl succinate. Differential scanning calorimetry was used to compare the effectiveness of the inhibitors in a curable formulation composed of vinyl-stopped-polydimethyl siloxane, polydimethylsiloxanemethylhydrogen-copolymer, a platinum catalyst and either a maleate or fumarate inhibitor.