ABSTRACT
The ΔP(-)PBS analog of the DNA primary binding sequence (PBS) of the HIV-1 genome labeled at different positions by 2-aminopurine (2-AP) is investigated by a novel femtosecond fluorescence down-conversion experiment with 0.3-ps time resolution. The high signal-to-noise ratio of the fluorescence kinetics makes it possible to reveal four distinct decay times ranging from 0.8 ps to 2-3 ns for all the three labeling positions. This suggests the existence of at least four different quenching conformations of 2-AP with its nearest neighbors, and underscores the structural heterogeneity of the loop region of ΔP(-)PBS. Sub-5-ps components are found and attributed to stacking interactions of 2-AP with the flanking guanine (G) side chains, consistent with the NMR structure of ΔP(-)PBS. The observation of a significant increase of their total amplitude when 2-AP is positioned close to the rigid 3'-half of the G-rich stem gives further support to this assignment. Only a minor portion of conformations involves slow nanosecond collisional quenching.
Subject(s)
2-Aminopurine/chemistry , DNA, Viral/chemistry , Guanine/chemistry , HIV-1/chemistry , Inverted Repeat Sequences , Fluorescence , Humans , Kinetics , Nucleic Acid Conformation , Oligonucleotides/chemistry , Signal-To-Noise Ratio , Solutions , Spectrometry, Fluorescence , Thermodynamics , Time FactorsABSTRACT
Cobalt, nickel, copper and zinc coordination compounds of two thiosemicarbazones with general composition ML(2) (L: monodeprotonated ligand corresponding to 2-acetyl-gamma-butyrolactone thiosemicarbazone, HL(1), and 2-furancarbaldehyde thiosemicarbazone, HL(2)) and also complexes with general composition MCl(2)(HL(2)) were synthesized (except [NiCl(2)(HL(2))] and [Co(L(2))(2)]). The interaction of CuCl(2) with HL(2) gave [CuCl(HL(2))], a copper(I) complex. The ligands and metal complexes were characterized by IR, (1)H and (13)C NMR spectroscopy, and magnetic susceptibility measurements. The crystal structure of [Ni(L(2))(2)]x 2dmso was determined and a trans-square planar coordination of the two kappa(2)-N,S chelate rings forming polymeric strips through H-bonds with dmso was observed. Actually, in all the reported complexes both ligands behaved as kappa(2)-N,S chelates, except in the case of [Co(L(1))(2)] in which HL(1) is tridentate kappa(3)-N,S,O. The antimicrobial properties of all compounds were studied using a wide spectrum of bacterial and fungal strains. The copper complexes of HL(2) were the most active against all strains, including dermatophytes and phytopathogenic fungi. Most of the studied compounds, especially [Cu(L(1))(2)], presented good activity against Haemophilus influenzae, a very harmful bacterium to humans.
Subject(s)
4-Butyrolactone/pharmacology , Aldehydes/pharmacology , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Furans/pharmacology , Thiosemicarbazones/pharmacology , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , Aldehydes/chemical synthesis , Aldehydes/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Bacteria/drug effects , Cobalt/chemistry , Copper/chemistry , Crystallography, X-Ray , Fungi/drug effects , Furans/chemical synthesis , Furans/chemistry , Nickel/chemistry , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/chemistry , Zinc/chemistryABSTRACT
Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin (HL(1) and HL(2), respectively) were synthesized and characterized, being the crystal structures of HL(1), HL(2) and [Ni(L(1))(2)].2CHCl(3) elucidated by X-ray diffraction techniques. The in vitro antimicrobial activity of all these compounds was tested against several bacteria and fungi. HL(1)and its complexes exhibited a strong inhibition of the growth of Haemophilus influenzae (MIC 0.15-1.50microg/mL) and good antibacterial properties towards Bacillus subtilis (MIC 3-25microg/mL). The minimal inhibitory concentration (MIC) was defined as the lowest concentration of compound inhibiting the growth of each strain. The antibacterial effectiveness was confirmed against a number of Gram positive bacteria, including methicillin-resistant Staphylococcus aureus. Yeasts and moulds showed a low susceptibility, except the dermatophyte mould Epidermophyton floccosum that is inhibited at concentrations ranging from 6 to 50microg/mL. In general, the antimicrobial activity of the thiophene derivatives was greater than that of the isonicotinic analogues.
