SuperLigands – a database of ligand structures derived from the Protein Data Bank

Background  

Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function.     

Mesogenic and magnetic properties of nickel(II) complexes formed from 2′-(4-alkyloxyphenyl)malondialdehydes

The synthesis, characterization, thermal behavior and magnetic properties of a number of bis[2-(4-alkyloxyphenyl)malondialdehyde] nickel(II) complexes are reported. X-ray studies of the nickel(II) complexes were performed. It was found that the nickel(II) complexes show liquid-crystalline smectic A phases over a broad temperature range with low melting points. The temperature-dependent magnetic susceptibility measurements of the bis[2-(4-decyloxyphenyl)malondialdehyde] nickel(II) complex were carried out in the range of 4.2–480 K. The temperature dependent magnetic susceptibilities and magnetic moments of this compound (_eff=3.27 _B at 300 K) indicate that the nickel centers are octahedrally coordinated. Models for the molecular arrangement in the crystalline and liquid-crystalline phases are discussed on the basis of the magnetic data. In spite of the oxygen bridge between the nickel centers, no exchange interactions were found in the crystalline and liquid-crystalline phases.     

In-vitro antibacterial,antifungal activity of some transition metal complexes of thiosemicarbazone Schiff base (HL) derived from N4-(7′-chloroquinolin-4′-ylamino) thiosemicarbazide

The synthetic, spectroscopic, and biological studies of Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Fe(III) and Cr(III) complexes of N⁴-(7′-chloroquinoline-4′-ylamino)-N¹-(2-hydroxy-benzylidene)thiosemicarbazone (HL) obtained by the reaction of N⁴-(7′-chloroquinolin-4′-ylamino)thiosemicarbazide with 2-hydroxybenzaldehyde. The structures of the complexes were determined on the basis of the elemental analyses, spectroscopic data (IR, electronic, ¹H and ¹³C NMR and Mass spectra) along with magnetic susceptibility measurements, molar conductivity and thermogravimetric analyses. Electrical conductance measurement revealed the non-electrolytic nature of the complexes. The resulting colored products are mononuclear in nature. On the basis of the above studies, only one ligand was suggested to be coordinated to each metal atom by thione sulfur, azomethine nitrogen and phenolic oxygen to form mononuclear complexes in which the thiosemicarbazone behaves as a monobasic tridendate ligand. The ligand and its metal complexes were tested against Gram + ve bacteria (Staphylococcus aureus), Gram ? ve bacteria (Escherichia coli), fungi (Candida albicans) and (Fusarium solani). The tested compounds exhibited significant activity.     

Reversible switching of coordination modes of nickel(ΙΙ) complexes using a hemilabile 4,7-diazadecanediamide ligand

The reaction of NiCl₂·6H₂O with a hemilabile diaminodiamide ligand 4,7-diazadecanediamide gave a pale blue compound [Ni(C₈H₁₈N₄O₂)(H₂O)₂]·2Cl (1). In basic solution, 1 was transformed to a yellow species [Ni(C₈H₁₆N₄O₂)]·3H₂O (2) by the Ni-O to Ni-N bond rearrangement at two amide sites of the complex. Structures of 1 and 2 were characterized by single-crystal X-ray diffraction analysis. Structural data for 1 indicated that the nickel atom adopts a six-coordinated N₂O₄ environment and gives an octahedral geometry. The structure of 2 showed that the nickel atom adopts a four-coordinated N₄ environment, giving a square-planar geometry. Compounds 1 and 2 are structurally switchable in response to pH in an aqueous solution. The results presented could be useful in the design of new Ni(II)-based switching materials.     

Dioxo-, oxothio- and dithio-tungsten(VI) and tungsten(V) complexes of the ligand N,N′-Dimethyl-N,N′-bis(2-mercaptophenyl)ethylenediamine

Synthesis of complexes cis,cis-W^VOXL (X=Cl, NCS), cis,trans-W^VOXL (X=Cl, OPh, SPh) and cis,trans-W^VIE₂L (E₂=O₂, OS, S₂) of the title ligand LH₂ are reported. cis,cis-W^VOCIL crystallises in space group P2₁/c with a=13.6541(9) Å, b=7.1555(11) Å, c=18.198(2) Å, β=95.294(6)°, V=1770.4(3) ų and Z=4 while the cis,trans isomer crystallises in space group P2₁/n with a=10.361(3) Å, b=14.141(4) Å, c=12.213(5) Å, β=102.56(3)°, V=1747(2) ų and Z=4. cis,trans-W^VIS₂L crystallises in space group P2₁/n with a=10.645(2) Å, b=13.929(2) Å, c=12.189(2) Å, β=103.14(2)°, V=1760(1) ų and Z=4. A short CH₃···Cl distance of 3.067(7) Å and an acute OWCl angle of 94.1(2)° are seen in cis,cis-W^VOClL, which converts to the cis,trans form on heating in MeCN. The latter isomer features a CH₃···Cl distance of 3.38(2) Å and an OWCl angle of 105.1(8)°. Electrochemical and EPR data are reported. In particular, cis,trans-W^VIE₂L may be reduced to [W^VE₂L]^–. EPR properties of these anions and those of complexes W^VOXL are discussed in the context of W^V centres in tungsten enzymes.     

He(I) and He(II) photoelectron spectra of Hyprrole-2-CHN′t-Bu and the biscarbonyl Rh(I) and Ir(I) complexes of its anion

The He(I) and He(II) photoelectron spectra of a series of [(LL)M(CO)₂] (LL = pyrrole-2-CHN′ R; R = t-Bu; M = Rh, Ir) complexes are reported. Assignments are proposed based on He(I)/He(II) intensity differences, on molecular orbital calculations of related complexes and of free ligands, and by comparison with the spectra of the free ligands Hpyrrole-2-CHN′t-Bu, Hpyrrole-2-carbaldehyde and Hpyrrole.The electronic structure of the complexes is discussed and conclusions are drawn about the metal-ligand interaction.     

Multispectroscopic DNA-binding studies of a terbium(III) complex containing 2,2′-bipyridine ligand

Agarose gel electrophoresis, absorption, fluorescence, viscosity, and circular dichroism (CD) have been used in exploring the interaction of terbium(III) complex, [Tb(bpy)₂Cl₃(OH₂)] where bipy is 2,2′-bipyridine, with Fish salmon DNA. Agarose gel electrophoresis assay, along with absorption and fluorescence studies, reveal interaction between the corresponding complex and FS-DNA. Also, the binding constants (K_b) and the Stern–Volmer quenching constants (K_sv) of Tb(III) complex with FS-DNA were determined. The calculated thermodynamic parameters suggested that the binding of mentioned complex to FS-DNA was driven mainly by hydrophobic interactions. A comparative study of this complex with respect to the effect of iodide-induced quenching, ionic strength effect, and ethidium bromide exclusion assay reflects binding of explicit to the FS-DNA primarily in a groove fashion. CD and viscosity data also support the groove binding mode. Furthermore, Tb(III) complex have been simultaneously screened for their antibacterial and antifungal activities.     

Novel aminopeptidase N inhibitors derived from antineoplaston AS2–5 (Part I)

Overexpression of zinc-dependent metalloproteinase, aminopeptidase N (APN/CD13), is considered to be involved in the process of tumor invasion and metastasis. Herein we describe the synthesis and in vitro enzymatic inhibition assay of antineoplaston AS2–5 scaffold peptidomimetic compounds. The results demonstrated that most of these l-iso-glutamine derivatives displayed selective inhibitory activity against APN as compared with MMP-2, with IC₅₀ values in the micromole range. The structure–activity relationships were also briefly discussed.     

Carbonyl complexes of Rh(I), Ir(I) and Mo(0) containing substituted derivatives of 1,10-phenanthroline and 2,2′-bipyridine

The A₁ symmetry v_CO of the carbonyl complexes [Mo(chel)(CO)₄], [M(chel)(CO)₂] [PF₆] (M=Rh, Ir; chel=bipy, phen and substituted derivatives) are used for determining the electron donor-acceptor properties of the title ligands. The steric hindrance of the methyl groups in positions 2 and 9 of the phenanthroline favours the formation of Rh(I) and Ir(I) pentacoordinated derivatives.     

Oxoiron(IV) complexes of the tris(2-pyridylmethyl)amine ligand family: effect of pyridine α-substituents

The oxoiron(IV) complexes of two 6-substituted tris(2-pyridylmethyl)amine ligand derivatives have been generated and characterized with respect to their spectroscopic and reactivity properties. The introduction of an α-substituent maintains the low-spin nature of the oxoiron(IV) unit but weakens the ligand field, as evidenced by red shifts in its characteristic near-IR chromophore. While its hydrogen-atom abstraction ability is only slightly affected, the oxo-transfer reactivity of the oxoiron(IV) center is significantly enhanced relative to that of the parent complex. These results demonstrate that the ligand environment plays a key role in modulating the reactivity of this important biological oxidant. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. An erratum to this article can be found at     

A binuclear copper(II) complex of the schiff base derived from 1,1′-(2,6-pyridyl)-bis-1,3-butanedione and 3-amino-1-propanol

The reaction of Cu(ClO₄)₂·6H₂O with the Schiff base derived from 1,1′-(2,6-pyridyl)-bis-1,3-butanedione and 3-amino-1-propanol, (H₄L²), yields the complex Cu(H₄L²)(ClO₄)₂·H₂O. The crystal structure of this complex is triclinic, R = 0.0521, 5602 reflections. The species is dimeric leading to a binuclear copper(II) complex in which the well- separated (8.93 Å intramolecular and 5.46 Å inter- molecular) copper(II) atoms are in distorted square pyramidal geometries.     

Reactions of metal complexes with carbohydrates: Synthesis and characterization of novel nickel(II) complexes containing glycosylamines derived from a monosaccharide and a diamine. An X-ray crystallographic study of (ethylenediamine) {N-(2-aminoethyl)-d-fructopyranosylamine} nickel(II) · Cl2 · CH3OH

Tris(ethylenediamine)- or tris(trimethylenediamine)-nickel(II) salts react with d-glucose, d-mannose, or d-fructose to give novel, octahedral, nickel(II) complexes containing glycosylamine(s) derived from the reaction of the monosaccharide with the diamine. The complexes have been characterized by elemental analysis, magnetic susceptibility, and electronic absorption, infrared, and circular dichroism spectra. The complexes from aldoses contain two sugar entities, and those from a ketose have one sugar unit. The X-ray crystal structure was determined of one of the products, in which N-(2-aminoethyl)-d-fructopyranosylamine and ethylenediamine are coordinated to a nickel ion. Crystal data for the compound: a = 12.348(5) Å, b = 18.478(8) Å, c = 8.464(4) Å, Z = 4, space group P2₁2₁2₁, 2348 unique observed reflections [Fo > 3σ(Fo)] used in the structure analysis, R = 0.068, Rw = 0.053. The sugar is coordinated to the nickel ion at three points, through the 1- and 3-hydroxyl groups and the nitrogen atom on C-2.     

Biochemical characterization of CK2α and α′ paralogues and their derived holoenzymes: evidence for the existence of a heterotrimeric CK2α′-holoenzyme forming trimeric complexes

Altogether 2 holoenzymes and 4 catalytic CK2 constructs were expressed and characterized i.e. CK2alpha (2) (1-335) beta(2); CK2alpha'-derived holoenzyme; CK2alpha(1-335); MBP-CK2alpha'; His-tagged CK2alpha and His-tagged CK2alpha'. The two His-tagged catalytic subunits were expressed in insect cells, all others in Escherichia coli. IC(50) studies involving the established CK2 inhibitors DMAT, TBBt, TBBz, apigenin and emodin were carried out and the K(i) values calculated. Although the differences in the K(i) values found were modest, there was a general tendency showing that the CK2 holoenzymes were more sensitive towards the inhibitors than the free catalytic subunits. Thermal inactivation experiments involving the individual catalytic subunits showed an almost complete loss of activity after only 2 min at 45 degrees C. In the case of the two holoenzymes, the CK2alpha'-derived holoenzyme lost ca. 90% of its activity after 14 min, whereas CK2alpha (2) (1-335) beta(2) only showed a loss of ca. 40% by this time of incubation. Gel filtration analyses were performed at high (500 mM) and low (150 mM) monovalent salt concentrations in the absence or presence of ATP. At 500 mM NaCl the CK2alpha'-derived holoenzyme eluted at a position corresponding to a molecular mass of 105 kDa which is significantly below the elution of the CK2alpha (2) (1-335) beta(2) holoenzyme (145 kDa). Calmodulin was not phosphorylated by either CK2alpha (2) (1-335) beta(2) or the CK2alpha'-derived holoenzyme. However, in the presence of polylysine only the CK2alpha (2) (1-335) beta(2) holoenzyme could use calmodulin as a substrate such as the catalytic subunits, in contrast to the CK2alpha'-derived holoenzyme which only phosphorylated calmodulin weakly. This attenuation may be owing to a different structural interaction between the catalytic CK2alpha' subunit and non-catalytic CK2beta subunit.     

Identification of 2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide as a Sodium Valproate-like broad spectrum anti-epileptic drug candidate

By further optimizing compound A [2′-fluoro-N-methyl-[1,1′-biphenyl]-2-sulfonamide], we identified DSP-0565 [2-(2′-fluoro-[1,1′-biphenyl]-2-yl)acetamide, 17a] as a strong, broad-spectrum anti-epileptic drug (AED) candidate. Our efforts mainly focused on finding an alternative polar group for the sulfonamide in order to improve ADME profile of compound A including good metabolic stability and no reactive metabolic production. This led to the identification of biphenyl acetamide as a new scaffold for development of broad-spectrum AED candidates. DSP-0565 showed anti-convulsant activity in various models (scPTZ, MES, 6?Hz and amygdala kindling) with good safety margin, and was therefore selected as a clinical candidate.     

Aqueous Synthesis of Peptide Thioesters from Amino Acids and a Thiol Using 1,1′-Carbonyldiimidazole

A new method was developed for the synthesis of peptide thioesters from free amino acids and thiols in water. This one-pot simple method involves two steps: (1) activation in water of an amino acid presumably as its N-carboxyanhydride (NCA) using 1,1′-carbonyldiimidazole (CDI), and (2) subsequent condensation of the activated amino acid-NCA in the presence of a thiol. With this method citrulline peptide thioesters containing up to 10 amino acid residues were prepared in a single reaction. This aqueous synthetic method provides a simple way to prepare peptide thioesters for studies of peptide replication involving ligation of peptide thioesters on peptide templates. The relevance of peptide replication to the origin-of-life process is supported by previous studies showing that amino acid thioesters (peptide thioester precursors) can be synthesized under prebiotic conditions by reaction of small sugars with ammonia and a thiol.     

Synthesis of 2′ -Deoxypyrihidine Nucleosides Via Copper (I) Iodide Catalysis

Abstract

The high current interest in the use of 2′-deoxypyrimidine nucleosides as potential anti-viral agents has made a high-yield route favoring the biologically active 8-anocaers deslrable. To this end the coupling of pyrimidine with 2 in EDC or CHC1, was studied using weak Lewis Acid catalysts. Of the catalysts studied only copper (I) iodide gave 6-selective reactions.