Synthesis and glutathione peroxidase (GPx)-like activity of selenocystine (SeC) bioconjugates of biotin and lipoic acid.

The conjugation of active biomolecules provides insight into their bioreactivity, leading to many applications in biotechnology and materials science. Herein, we report L-selenocystine (SeC) bioconjugates of lipoic acid (universal antioxidant) and biotin (Vitamin-H). The SeC-bioconjugates, SeC-Biotin (1) and SeC-Lipoic acid (2) were synthesized using solid phase peptide synthesis (SPPS) method and were characterized by multinuclear 1D (1H, 13C, 77Se) and 2D (1H-1H COSY and 1H-13C TOCSY) NMR spectroscopy, ESI-MS spectrometry, and RP-HPLC. The GPx-like enzyme mimicking activity of the SeC-bioconjugates 1 and 2 has been investigated through the coupled reductase assay method for the catalytic reductions of hydrogen peroxide into water. A significant enhancement in GPx-like enzymatic activity was observed for both novel bioconjugates SeC-Biotin (1) and SeC-Lipoic acid (2) as compared to diphenyl diselenide (Ph2Se2), L-selenocystine (SeC), biotin, lipoic acid, and ebselen.

Coordination Behavior of the Tellurium Incorporated Mercuraazametallamacrocycle and Investigation of d10 ⋠⋠⋠d10 Interactions between Closed Shell (Ag+ Hg2+ ) Metal Ions.

Herein, a new tellurium and mercury containing mercuraazametallamacrocycle has been prepared via (2+2) condensation of bis(o-aminophenyl)telluride and bis(o-formylphenyl)mercury(II). The isolated bright yellow solid of mercuraazametallamacrocycle has adopted unsymmetrical figure-of-eight conformation in the crystal structure. To study the metallophilic interactions between closed shell metal ions, the macrocyclic ligand has been treated with two equiv. of AgOTf (OTf=trifluoromethansulfonate) and AgBF4 , which afforded greenish-yellow bimetallic silver complexes. The isolated silver complexes displayed intramolecular Hg⋅⋅⋅Ag, Te⋅⋅⋅Ag interactions as well as intermolecular Hg⋅⋅⋅Hg interactions and formed an extended 1D molecular chain by directing six atoms to interact as TeII ⋅⋅⋅AgI ⋅⋅⋅HgII ⋅⋅⋅HgII ⋅⋅⋅AgI ⋅⋅⋅TeII in a non linear fashion. The Hg⋅⋅⋅Ag, Te⋅⋅⋅Ag interactions have also been studied in solution by 199 Hg, 125 Te NMR spectroscopy, absorption, and emission spectroscopy. In DFT calculations, the Atom in Molecule (AIM) analysis, non-covalent interactions (NCI), natural bonding orbital (NBO) analysis strongly supported for experimental evidences and revealed that the intermolecular Hg⋅⋅⋅Hg interaction is stronger than the intramolecular Hg⋅⋅⋅Ag interactions.

Pushing the Boundary of Covalency in Lanthanoid-Tellurium Bonds: Insights from the Synthesis, Molecular and Electronic Structures of Low-Coordinate, Monomeric Europium(II) and Ytterbium(II) Tellurolates.

Owing to the strict hard/soft dichotomy between the lanthanoids and tellurium atoms, and the strong affinity of lanthanoid ions for high coordination numbers, low-coordinate, monomeric lanthanoid tellurolate complexes have remained elusive as compared to the lanthanoid complexes with lighter group 16 elements (O, S, and Se). This makes the development of suitable ligand systems for low-coordinate, monomeric lanthanoid tellurolate complexes an appealing endeavor. In a first report, a series of low-coordinate, monomeric lanthanoid (Yb, Eu) tellurolate complexes were synthesized by utilizing hybrid organotellurolate ligands containing N-donor pendant arms. The reaction of bis[2-((dimethylamino)methyl)phenyl] ditelluride, 1 and 8,8'diquinolinyl ditelluride, 2 with Ln0 metals (Ln=Eu, Yb) resulted in the formation of monomeric complexes [LnII (TeR)2 (Solv)2 ] [R=C6 H4 -2-CH2 NMe2 ] [3: Ln=Eu, Solv=tetrahydrofuran; 4: Ln=Eu, Solv=acetonitrile; 5: Ln=Yb, Solv=tetrahydrofuran; 6: Ln=Yb, Solv=pyridine] and [EuII (TeNC9 H6 )2 (Solv)n ] (7: Solv=tetrahydrofuran, n=3; 8: Solv=1,2-dimethoxyethane, n=2), respectively. Complexes 3-4 and 7-8 represent the first sets of examples of monomeric europium tellurolate complexes. The molecular structures of complexes 3-8 are validated by single-crystal X-ray diffraction studies. The electronic structures of these complexes were investigated using Density Functional Theory (DFT) calculations, which revealed appreciable covalency between the tellurolate ligands and lanthanoids.

Chalcogen Bonds in Selenocysteine Seleninic Acid, a Functional GPx Constituent, and in Other Seleninic or Sulfinic Acid Derivatives.

The controlled oxidation reaction of L-selenocystine under neutral pH conditions affords selenocysteine seleninic acid (3-selenino-L-alanine) which is characterized also by means of single-crystal X-ray diffraction. This technique shows that selenium forms three chalcogen bonds (ChBs), one of them being outstandingly short. A survey of seleninic acid derivatives in the Cambridge Structural Database (CSD) confirms that the C-Se(=O)O- functionality tends to act as a ChB donor robust enough to systematically influence the interactional landscape in the solid. Quantum Theory of Atom in Molecules (QTAIM) analysis proves the attractive nature of the short contacts observed in crystals containing the seleninic functionality and calculation of surface molecular electrostatic potential (MEP) reveals that remarkably positive σ-holes can frequently be found opposite to the covalent bonds at selenium. Both CSD searches and QTAIM and MEP approaches show that also the sulfinic acid moiety can function as a ChB donor, albeit less frequently than the seleninic acid one. These findings may contribute to a better understanding, at the atomic level, of the mechanism of action of the enzymes that control oxidative stress and ROS deactivation and that contain selenocysteine seleninic acid and cysteine sulfinic acid in the active site.

Bis(2-nitrophenyl) selenide, bis(2-aminophenyl) selenide and bis(2-aminophenyl) telluride: structural and theoretical analysis.

Three organoselenium and organotellurium compounds containing ortho substitutents, namely, bis(2-nitrophenyl) selenide, C12H8N2O4Se, 2, bis(2-aminophenyl) selenide, C12H12N2Se, 3, and bis(2-aminophenyl) telluride, C12H12N2Te, 7, have been investigated by both structural and theoretical methods. In the structures of all three compounds, there are intramolecular contacts between both Se and Te with the ortho substituents. In the case of 2, this is achieved by rotation of the nitro group from the arene plane. For 3, both amino groups exhibit pyramidal geometry and are involved in intramolecular N-H...Se interactions, with one also participating in intermolecular N-H...N hydrogen bonding. While 3 and 7 are structurally similar, there are some significant differences. In addition to both intramolecular N-H...Te interactions and intermolecular N-H...N hydrogen bonding, 7 also exhibits intramolecular N-H...N hydrogen bonding. In the packing of these molecules, for 2, there are weak intermolecular C-H...O contacts and these, along with the O...N interactions mentioned above, link the molecules into a three-dimensional array. For 3, in addition to the N-H...N and N-H...Se interactions, there are also weak intermolecular C-H...Se interactions, which also link the molecules into a three-dimensional array. On the other hand, 7 shows intermolecular N-H...N interactions linking the molecules into R22(16) centrosymmetric dimers. In the theoretical studies, for compound 2, AIM (atoms in molecules) analysis revealed critical points in the Se...O interactions with values of 0.017 and 0.026 a.u. These values are suggestive of weak interactions present between Se and O atoms. For 3 and 7, the molecular structures displayed intramolecular, as well as intermolecular, hydrogen-bond interactions of the N-H...N type. The strength of this hydrogen-bond interaction was calculated by AIM analysis. Here, the intermolecular (N-H...N) hydrogen bond is stronger than the intramolecular hydrogen bond. This was confirmed by the electron densities for 3 and 7 [ρ(r) = 0.015 and 0.011, respectively].

Self-Assembly of Nicotinic Acid-Conjugated Selenopeptides into Mesotubes.

The study of controlling the morphology for designing advanced supramolecular architectures by tuning the molecular motif at the elemental level has been rarely carried out. Here, we report the synthesis of a nicotinic acid-conjugated selenopeptide, which induced the formation of an unbranched mesoscale elongated tubular morphology. We rationally designed two additional peptides to find out the decisive role played by the nitrogen atom (in nicotinic acid) and selenium (in the peptide backbone) toward the formation of the mesotube. We found that the peptide, devoid of nitrogen, forms a fibrillar structure, whereas the peptide without selenium self-assembled into a cylindrical filled rodlike morphology. Here, we report an entirely different class of peptide inspired from the selenopeptide chemistry that forms a tubular structure and unambiguously establish that both nicotinic acid and selenium are essential toward the formation of such mesotubes.

Structure of a diorganotelluroxonium(IV) cation, {[2,6-(CH2NMe2)2C6H3Te(µ-O)]2}2+, with the tri-chlorido-(dimethyl sulfoxide)-platinum(II) anion.

In the title salt, di-µ-oxido-bis-{2,6-bis-[(di-methyl-amino)-meth-yl]phenyl-κC 1}tellurium(-IV) bis[tri-chlorido-(dimethyl sulfoxide-κS)platinate(II)], (C24H38N4O2Te2)[PdCl3(C2H6OS)]2, which crystallizes in the triclinic space group P , each Te atom is in a distorted five-coordinated TeO2N2C square-pyramidal geometry (τ values of 0.026 and 0.001) with the C atoms of the phenyl rings occupying the apical positions. The phenyl rings in the [C24H38N4O2Te2]2+ cation are in a cis arrangement to enable this species to participate in Te⋯Cl cation-anion inter-actions. There are also C-H⋯O inter-actions involving the dimethyl sulfoxide ligands and numerous cation-anion and anion-anion C-H⋯Cl inter-actions, which link the ions into a complex three-dimensional array.

Structural characterization of the derivatives of bis{[2,6-(dimethylamino)methyl]phenyl} selenide with palladium(II) and mercury(II).

The intramolecularly coordinated homoleptic diorgano selenide bis{2,6-bis[(dimethylamino)methyl]phenyl} selenide, C24H38N4Se or R2Se, where R is 2,6-(Me2NCH2)2C6H3, 14, was synthesized and its ligation reactions with PdII and HgII precursors were explored. The reaction of 14 with SO2Cl2 and K2PdCl4 resulted in the formation of the meta C-H-activated dipalladated complex {µ-2,2'-bis[(dimethylamino)methyl]-4,4'-bis[(dimethylazaniumyl)methyl]-3,3'-selanediyldiphenyl-κ4C1,N2:C1',N2'}bis[dichloridopalladium(II)], [Pd2Cl4(C24H38N4Se)] or [{R(H)PdCl2}2Se], 15. On the other hand, when ligand 14 was reacted with HgCl2, the reaction afforded a dimercurated selenolate complex, {µ-bis{2,6-bis[(dimethylamino)methyl]benzeneselanolato-κ4N2,Se:Se,N6}-µ-chlorido-bis[chloridomercury(II)], [Hg2(C12H19N2Se)Cl3] or RSeHg2Cl3, 16, where two HgII ions are bridged by selenolate and chloride ligands. In palladium complex 15, there are two molecules located on crystallographic twofold axes and within each molecule the Pd moieties are related by symmetry, but there are still two independent Pd centers. Mercury complex 16 results from the cleavage of one of the Se-C bonds to form a bifurcated SeHg2 moiety with the formal charge on the Se atom being -1. In addition, one of the Cl ligands bridges the two Hg atoms and there are two terminal Hg-Cl bonds. Each Hg atom is in a distorted environment which can be best described as a T-shaped base with the bridging Cl atom in an apical position, with several angles close to 90° and with one angle much larger and closer to 180°.

Metallophilic interactions: observations of the shortest metallophilicinteractions between closed shell (d10d10, d10d8, d8d8) metal ions [MM' M = Hg(ii) and Pd(ii) and M' = Cu(i), Ag(i), Au(i), and Pd(ii)].

The salt metathesis reaction of two equivalents of 8-lithioquinoline (C6H6NLi) with HgBr2 afforded bis(quinoline-8-yl)mercury, [(C6H6N)2Hg]. Bis(quinoline-8-yl)mercury has been used for the synthesis of a series of heteronuclear complexes of the type [(C6H6N)2M·M']·X-n [M = Hg; {M' = Cu, X- = ClO4; X = I; X- = CF3SO3}, {M' = Ag, X- = ClO4; X- = CF3SO3; X- = BF4}, {M' = Au, X- = CF3SO3}; {M' = Pd, X- = CF3CO2}], [M = Pd; M' = Pd, X- = CF3CO2; n = 2]. All the complexes were well characterized by multinuclear NMR (1H, 13C, 19F, 11B, 199Hg) spectroscopic analysis. Their structures were determined by single crystal X-ray diffraction studies, which displayed the shortest HgM' (M' = Cu, Ag, Au, Pd) metallophilic interactions. The electronic properties of the molecular structures were determined by DFT calculations. ELF (Electron Localization Function) analysis provided the information about the localization of electrons between metalmetal bonds and dispersion of electron density around the metal ions. The AIM (Atoms in Molecule) analysis revealed the presence of electron density at the bond critical points (bcp) and the strengths of MM' [M = Hg, M' = Cu, Ag, Au, Pd; M, M'=Pd] interactions. The NBO (Natural Bond Orbital) analysis was used to identify the donor-acceptor character of the orbitals involved in the bonding.

Isolation of the novel example of a monomeric organotellurinic acid.

The stoichiometrically controlled alkaline hydrolysis of 4, (ppy)TeCl3, [ppy = 2-(2'-pyridyl)phenyl] afforded the partially hydrolyzed µ-oxo-bridged dinuclear telluroxane 5, [(ppyTeCl2)2(µ-O)] and a novel example of an Intramolecular Chalcogen Bonding (IChB) stabilized, monomeric organotellurinic acid 6, (ppy)Te(O)OH. The oxidation of diaryl ditelluride 7, (ppyTe)2 using H2O2 resulted in the isolation of µ-oxo-bridged dimethyl ester 8, [(ppy)Te(O)(OH)(OMe)]2(O). The molecular structures of 4-6 and 8 are unambiguously authenticated by single crystal X-ray diffraction studies. The electronic structure of monomeric tellurinic acid 6 is investigated using DFT calculations. The Natural Bond Order (NBO) analysis, in corroboration with Atoms in Molecules (AIM) analysis reveals that tellurinic acid 6 is stabilized by σ-hole participation of the tellurium atom with the pyridyl N-atom resulting in strong electrostatic interactions between the N and Te atoms.

Facile synthesis of stable selenocystine peptides and their solution state NMR studies.

A facile general route for the synthesis of various selenocystine tripeptides containing acidic, basic and neutral side chain amino acids is reported. Here, TFA labile side chain protected selenocysteine has been used as a precursor for the synthesis of selenopeptides. The peptides are highly stable in dimethyl sulphoxide, thus enabling detailed NMR studies by solution phase 1- and 2-dimensional NMR spectroscopy.

Oxidation behavior of intramolecularly coordinated unsymmetrical diorganotellurides: isolation of novel tetraorganoditelluronic acids, [RR'Te(µ-O)(OH)2]2.

The oxidation reaction of unsymmetrical diorganotellurides, namely, bis[2-{(dimethylamino)methyl}aryl]tellurides [aryl = phenyl (6), 2-methylphenyl (7), 2,6-dimethylphenyl (8) and 2,6-diisopropylphenyl (9)] with meta-chloroperbenzoic acid afforded the first examples of tetraorganoditelluronic acids, [RR'Te(µ-O)(OH)2]2, where R = 2-NMe2CH2C6H4, R' = C6H5 (10), 2-MeC6H4 (11), 2,6-MeC6H3 (12) and 2,6-iPrC6H3 (13). The structures of tetraorganoditelluronic acids 10-13 were authenticated by single crystal X-ray diffraction studies. From the molecular structures of 10-13, it was observed that the sp3 N-donor atoms, which were initially involved in intramolecular TeN bonding interactions in diorganotellurides 6-9, did not interact with the tellurium atoms in tetraorganoditelluronic acids 10-13. The 125Te chemical shifts for 10-13 were considerably downfield shifted as compared with the values observed for the corresponding tellurides 6-9. The relative stabilities of the tetraorganoditelluronic acids 10-13 with respect to their lighter analogues (S and Se) have been assessed using DFT calculations.

Isolation and structure of an 18-membered macrocycle containing two diselenide linkages and its precursor.

The structures of the 18-membered diselenide-linked macrocycle 10,27-di-tert-butyl 11,28-dioxo-2,3,19,20-tetraselena-10,12,27,29-tetraazapentacyclo[28.4.0.04,9.013,18.021,26]tetratriaconta-1(30),4(9),5,7,13,15,17,21,23,25,31,33-dodecaene-10,27-dicarboxylate, C36H34N4O6Se4, and its precursor di-tert-butyl 2,2'-[diselane-1,2-diylbis(2,1-phenylene)]dicarbamate, C22H28N2O4Se2, are reported. The precusor to the macrocycle contains two tert-butyl phenylcarbamate arms connected to a diselenide group, with Se-C and Se-Se bond lengths of 1.914 (4) and 2.3408 (6) Å, respectively. The macrocycle resides on a crystallographic center of inversion in space group P-1 with one molecule in the unit cell (Z' = 1/2). It contains an 18-membered macrocyclic ring with two diselenide linkages. In this macrocycle, there are two free and two protected amino groups.

Synthesis of selenopeptides: an alternative way of incorporating selenocystine.

Selenocysteine (Sec) residue cannot be directly attached to a peptide sequence unless the selenol form is protected beforehand and several problems have been reported in the preparation of Sec building blocks. In this article a series of selenocystine, the oxidized form of Sec, containing peptides has been synthesized using a new methodology, where Boc-NH-chloroalanine is coupled with methyl ester protected residues (Ala, Met, Phe) using DCC/HOBt as the coupling reagents providing di- and tripeptides. Further, the treatment of disodium diselenide with chloroalanine peptides (Boc-ClAla-Ala-OMe, Boc-ClAla-Met-OMe and Boc-ClAla-Ala-Phe-OMe) afforded the respective selenocystine-containing peptides (Boc-Sec-Ala-OMe, Boc-Sec-Met-OMe and Boc-Sec-Ala-Phe-OMe).

Hypervalent organoselenium compounds stabilized by intramolecular coordination: synthesis and crystal structures.

Two novel hypervalent selenium(IV) compounds stabilized by intramolecular interactions, namely 6-phenyl-6,7-dihydro-5H-2,3-dioxa-2aλ4-selenacyclopenta[hi]indene, C14H12O2Se, 14, and 5-phenyl-5,6-dihydro-4H-benzo[c][1,2]oxaselenole-7-carbaldehyde, C14H12OSe2, 15, have been synthesized by the reaction of 2-chloro-1-formyl-3-(hydroxymethylene)cyclohexene with in-situ-generated disodium diselenide (Na2Se2). The title compounds were characterized by FT-IR spectroscopy, ESI-MS, and single-crystal X-ray diffraction studies. For 14, there is whole-molecule disorder, with occupancies of 0.605 (10) and 0.395 (10), a double bond between C and Se, and the five-membered selenopentalene rings are coplanar. The packing is stabilized by π-π stacking interactions involving one of the five-membered Se/C/C/C/O rings [centroid-centroid (Cg...Cg) distance = 3.6472 (18) Šand slippage = 1.361 Å], as well as C-H...π interactions involving a C-H group and the phenyl ring. In addition, there are bifurcated C-H...Se,O interactions which link the molecules into ribbons in the c direction. For 15, the C-Se bond lengths are longer than those of 14. The two five-membered rings are coplanar. There are no π-π or C-H...π interactions; however, molecules are linked by C-H...O interactions into centrosymmetric dimers, with graph-set notation R22(16).

Adaptive responses of sterically confined intramolecular chalcogen bonds.

The responsive behavior of an entity towards its immediate surrounding is referred to as an adaptive response. The adaptive responses of a noncovalent interaction at the molecular scale are reflected from its structural and functional roles. Intramolecular chalcogen bonding (IChB), an attractive interaction between a heavy chalcogen E (E = Se or Te) centered sigma hole and an ortho-heteroatom Lewis base donor D (D = O or N), plays an adaptive role in defining the structure and reactivity of arylchalcogen compounds. In this perspective, we describe the adaptive roles of a chalcogen centered Lewis acid sigma hole and a proximal Lewis base (O or N) in accommodating built-in steric stress in 2,6-disubstituted arylchalcogen compounds. From our perspective, the IChB components (a sigma hole and the proximal Lewis base) act in synergism to accommodate the overwhelming steric force. The adaptive responses of the IChB components are inferred from the observed molecular structures and reactivity. These include (a) adaptation of a conformation without IChBs, (b) adaptation of a conformation with weak IChBs, (c) twisting the skeletal aryl ring while maintaining IChBs, (d) ionization of the E-X bond (e.g., X = Br) to relieve stress and (e) intramolecular cyclization to relieve steric stress. A comprehensive approach, involving X-ray data analysis, density functional theory (DFT) calculations, reaction pattern analysis and principal component analysis (PCA), has been employed to rationalize the adaptive behaviors of IChBs in arylchalcogen compounds. We believe that the perception of ChB as an adaptive/stimulus responsive interaction would profit the futuristic approaches that would utilise ChB as self-assembly and molecular recognition tools.

Self-assembly of penta-selenopeptides into amyloid fibrils.

Here, we report the synthesis of a penta-selenopeptide consisting of five benzyl protected selenocysteine residues. This selenopeptide was well characterized by both one- and two-dimensional (D) NMR spectroscopies. We find that the solution conformation is enriched with ß-sheet structures, which have a propensity to self-assemble and form amyloid fibrils.

Reactivity of Selenocystine and Tellurocystine: Structure and Antioxidant Activity of the Derivatives.

l-Selenocystine (5) and l-tellurocystine (6) have been prepared and the reactivity of these amino acids, i.e., oxidation of 5 and 6, has been performed at various pH values. Hydrogen peroxide was used as an oxidant and it was treated with 5 and 6 in excess in acidic and basic media. Compound 5, upon oxidation, afforded SeIV and SeVI products. Selenocysteic acid [HO3 SeCH2 CH(NH2 )COOH] 9, a novel SeVI compound, was isolated and characterised by single-crystal X-ray diffraction studies. In contrast, l-tellurocystine, upon oxidation with H2 O2 , afforded TeII and TeIV products. Zwitterionic organotellurolate(IV), [TeCl3 CH2 CH(NH3 )COOH] 13, was isolated and characterised by NMR and IR spectroscopy, mass spectrometry and elemental analysis. Compound 13 crystallizes in an orthorhombic space group. l-Tellurocystine, when reduced with NaBH4 , produced the desired tellurolate intermediate, which was trapped with bromoacetic acid. Furthermore, l- and d-tellurocysteine derivatives, [(RTeCH2 CH(NH2 )COOH) R=phenyl, substituted phenyl and naphthyl (24-39)] were synthesised and evaluated for their glutathione peroxidase (GPx)-like activities. The results show that l-tellurocysteine derivatives have higher activity than their D-tellurocysteine analogues. DFT calculations for l-tellurocysteine derivatives provided information about the bond lengths and bond angles. This study reveals that the introduction of naphthyl substituents (35-38) leads to twisted conformation of the amino acid derivatives.

{N1-[2-(Butyl-selan-yl)benz-yl]-N2,N2-di-methyl-ethane-1,2-di-amine}-dichlorido-mercury(II).

In the title compound, [HgCl2(C16H28N2Se)], the primary geometry around the Se and Hg atoms is distorted trigonal-pyramidal and distorted square-pyramidal, respectively. The distortion of the mol-ecular geometry in the complex is caused by the steric demands of the ligands attached to the Se atom. The Hg atom is coordinated through two chloride anions, an N atom and an Se atom, making up an unusual HgNSeCl2 coordination sphere with an additional long Hg⋯N inter-action. Inter-molecular C-H⋯Cl inter-actions are the only identified inter-molecular hydrogen-bonding inter-actions that seem to be responsible for the self assembly. These relatively weak C-H⋯Cl hydrogen bonds possess the required linearity and donor-acceptor distances. They act as mol-ecular associative forces that result in a supra-molecular assembly along the b-axis direction in the solid state of the title compound.