Big flies, small repeats: the "Thr-Gly" region of the period gene in Diptera

The region of the clock gene period (per) that encodes a repetitive tract of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran species both within and outside the Drosophilidae. All the non- Drosophilidae sequences in this region are short and present a remarkably stable picture compared to the Drosophilidae, in which the region is much larger and extremely variable, both in size and composition. The accelerated evolution in the repetitive region of the Drosophilidae appears to be mainly due to an expansion of two ancestral repeats, one encoding a Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and asparagine or threonine. In some drosophilids the expansion involves a duplication of the pentapeptide sequence, but in Drosophila pseudoobscura both the dipeptide and the pentapeptide repeats are present in larger numbers. In the nondrosophilids, however, the pentapeptide sequence is represented by one copy and the dipeptide by two copies. These observations fulfill some of the predictions of recent theoretical models that have simulated the evolution of repetitive sequences.      

Synthetic analogue approach to metallobleomycins: syntheses, structure and properties of mononuclear and tetranuclear gallium(III) complexes of a ligand that resembles the metal-binding site of bleomycin

As part of our interest into the bioinorganic chemistry of gallium, gallium(III) complexes of the peptide ligand N-(2-(4-imidazolyl)ethyl)pyridine-2-carboxamide (pypepH2) resembling a fragment of the metal-binding domain of bleomycins (BLMs), have been isolated. Reaction of pypepH2 with (Et4N)[GaCl4] and Ga(acac)3 [acac- is the acetylacetonate(-1) ion] affords the mononuclear complex [Ga(pypepH)2]Cl.2H2O (1) and the tetranuclear complex [Ga4(acac)4(pypep)4].4.4H2O (2), respectively. Both complexes were characterized by single-crystal X-ray crystallography, IR spectroscopy and thermal decomposition data. The pypepH- ion in 1 behaves as a N(pyridyl), N(deprotonated amide), N(pyridine-type imidazole) chelating ligand. The doubly deprotonated pypep2- ion in 2 behaves as a N(pyridyl), N(deprotonated amide), N(imidazolate), N'(imidazolate) mu2 ligand and binds to one Ga(III) atom at its pyridyl, amide and one of the imidazolate nitrogens, and to a second metal ion at the other imidazolate nitrogen; a chelating acac- ligand completes six coordination at each Ga(III) centre. The IR data are discussed in terms of the nature of bonding and known structures. The 1H NMR spectrum of 1 suggests that the cation of the complex maintains its integrity in dimethylsulfoxide (DMSO) solution. Complexes 1 and 2 are the first synthetic analogues of metallobleomycins with gallium(III).     

Novel lipophilic amidate oxorhenium and oxotechnetium complexes as potential brain agents: synthesis, characterization and biological evaluation

Novel oxorhenium and oxotechnetium complexes based on the tetradentate 1-(2-hydroxybenzamido)-2-(pyridinecarboxamido)benzene, H3L, ligand have been synthesized and characterized herein. Thus, by reacting equimolar quantities of the triply deprotonated ligand L3- with the suitable MO3+ precursor, the following neutral MOL complexes could be easily produced following similar synthetic routes: M = Re (1), M = 99gTc (2), and M = 99mTc (3). Complexes 1 and 2, prepared in macroscopic amounts, were chemically characterized and their structure determined by single-crystal X-ray analysis. They are isostructural metal chelates, adopting a distorted square pyramidal geometry around the metal. The N3O donor atom set of the tetradentate ligand defines the basal plane and the oxygen atom of the M = O core occupies the apex of the pyramid. Complex 3 forms quantitatively at tracer level by mixing the H3L ligand with Na99mTcO4 generator eluate in aqueous alkaline media and using tin chloride as reductant in the presence of citrate. Its structure was established by chromatographic comparison with prototypic complexes 1 and 2 using high-performance liquid chromatographic techniques. When challenged with excess glutathione in vitro, complex 3 is rapidly converted to hydrophilic unidentified metal species. Tissue distribution data after administration of complex 3 in vivo revealed a significant uptake and retention of this compound in brain tissue.     

A nearly symmetric trinuclear chromium(III) oxo carboxylate assembly: preparation, molecular and crystal structure, and magnetic properties of [Cr3O(O2CPh)6(MeOH)3](NO3) · 2MeOH

Complex [Cr₃O(O₂CPh)₆(MeOH)₃](NO₃) · 2MeOH (1 · 2MeOH) has been synthesized from the one-pot reaction between Cr(NO₃)₃ · 9H₂O and NaO₂CPh in MeOH. The structure of the complex has been solved by single-crystal X-ray crystallography. It crystallizes in the monoclinic space group P2₁/n with a=14.716(6) Å, b=22.569(8) Å, c=15.755(6) Å, β=95.02(1)°, V=5212.5(4) ų and Z=4. Although the cation does not possess any crystallographically imposed symmetry element, its {Cr₃(μ₃-O)} core is nearly symmetric. Each Cr^III…Cr^III vector is further bridged by two η¹:η¹:μ₂ benzoates, with a terminal MeOH molecule completing octahedral coordination at each metal ion. The crystal structure consists of layers that are parallel to (0 1 0) crystallographic plane and are formed through π-π stacking interactions and hydrogen bonds. Variable-temperature magnetic susceptibility and solid-state ¹H NMR studies indicate that the total spin value of the ground state is 1/2. EPR experiments reveal the existence of a distribution of trimers with axial anisotropy in the g tensor.     

Zinc(II) complexes of the second-generation quinolone antibacterial drug enrofloxacin: Structure and DNA or albumin interaction

Zinc mononuclear complexes with the second-generation quinolone antibacterial drug enrofloxacin in the absence or presence of a nitrogen donor heterocyclic ligand 1,10-phenanthroline or 2,2′-bipyridine have been synthesized and characterized. Enrofloxacin is on deprotonated mode acting as a bidentate ligand coordinated to zinc ion through the ketone and a carboxylato oxygen atoms. The crystal structure of bis(enrofloxacinato)(1,10-phenanthroline)zinc(II), 2, has been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV and fluorescence spectroscopies. UV studies of the interaction of the complexes with DNA have shown that they can bind to CT DNA and the DNA binding constants have been calculated. Competitive studies with ethidium bromide (EB) have shown that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The complexes exhibit good binding propensity to human and bovine serum albumin proteins having relatively high binding constant values.     

Neutral and cationic mononuclear copper(II) complexes with enrofloxacin: structure and biological activity

The mononuclear copper complexes with the quinolone antibacterial drug enrofloxacin (=Herx) in the presence or not of a nitrogen donor heterocyclic ligand 1,10-phenanthroline (=phen) and 2,2'-bipyridine (=bipy) have been prepared and characterized. Interaction of copper(II) with deprotonated enrofloxacin leads to the formation of the neutral complex Cu(erx)2(H2O), 1, while the presence of phen or bipy leads to the formation of a neutral or a cationic mononuclear complex, respectively. The crystal structures of (chloro)(1,10-phenanthroline)(enrofloxacinato)copper(II), 2, and (aqua)(2,2'-bipyridine)(enrofloxacinato)copper(II) chloride, 3, have been determined with X-ray crystallography. The complexes have been studied with X-band electron paramagnetic resonance in aqueous solutions at liquid helium temperature. The study of the interaction of the complexes with calf-thymus DNA has been performed with diverse spectroscopic techniques and has showed that all complexes are bound to DNA by the intercalative mode. The antimicrobial efficiency of the complexes has been tested on three different microorganisms and the available evidence supports that the best inhibition is provided by Cu(erx)2(H2O) (minimum inhibitory concentration=0.125 microg mL(-1)) against Escherichia coli and Pseudomonas aeruginosa.     

Synthesis, structure and biological activity of copper(II) complexes with oxolinic acid

The neutral mononuclear copper complexes with the quinolone antibacterial drug oxolinic acid in the presence or not of a nitrogen donor heterocyclic ligand 1,10-phenanthroline, 2,2'-bipyridine or 2,2'-dipyridylamine have been synthesized and characterized with infrared, UV-visible and electron paramagnetic resonance spectroscopies. The experimental data suggest that oxolinic acid acts as a deprotonated bidentate ligand and is coordinated to the metal ion through the pyridone and one carboxylate oxygen atoms. The crystal structure of (chloro)(1,10-phenanthroline)(oxolinato) copper(II), 2, has been determined with X-ray crystallography. For all complexes a distorted square pyramidal environment around Cu(II) is suggested. The EPR (electron paramagnetic resonance) behavior of 2 in aqueous solutions indicates mixture of dimeric and monomeric species. The investigation of the interaction of the complexes with calf-thymus DNA has been performed with diverse spectroscopic techniques and showed that the complexes are bound to calf-thymus DNA. The antimicrobial activity of the complexes has been tested on three different microorganisms. The complexes show a decreased biological activity in comparison to the free oxolinic acid.