Oscar E. Piro

1,2,5-Oxadiazole N-oxide derivatives as potential anti-cancer agents: synthesis and biological evaluation. Part IV

Several new 1,2,5-oxadiazole N-oxide derivatives and some deoxygenated analogues were synthesized to be tested as potential selective hypoxic cell cytotoxins. Compounds prepared were designed in order to gain insight into the mechanism of action of this kind of cytotoxin. Compounds were tested in oxia and hypoxia and they proved to be non-selective. 3-Cyano-N(2)-oxide-4-phenyl-1,2,5-oxadiazole showed the best cytotoxic activity in oxia. The cytotoxicity observed for these derivatives could be explained in terms of the electronic characteristics of the 1,2,5-oxadiazole substituents. Electrochemical and ESR studies were performed on the more cytotoxic derivative.

Synthesis and characterization of three new Cu(II)-dipeptide complexes

Three new copper(II) complexes of stoichiometry [Cu(L-dipeptide)].nH(2)O, containing as ligands the dipeptides L-alanine-L-isoleucine, L-alanine-L-threonine and L-alanine-L-tyrosine were prepared. They were characterized by single crystal X-ray diffractometry, and electronic and infrared spectroscopy. In all cases, the Cu(II) cation has essentially the same elongated square pyramidal coordination, being equatorially cis coordinated by a N(2)O(2) arrangement of ligand atoms and axially by a carbonyl oxygen atom. The compounds show rather similar polymeric structures which resemble those recently reported for the [Cu(ala-val)] and [Cu(ala-phe)] complexes. The electronic and infrared spectra are briefly discussed on the basis of the structural peculiarities of the complexes. Superoxide dismutase (SOD)-like activity was also tested for the compounds.

Polarized infrared absorption spectra of Na2 [Fe (CN) 5NO] · 2H2O with part of the anions in the electronically excited metastable state

Abstract IR spectra of the nitroprusside ion in Na2[Fe (CN) 5NO]. 2H2O in the metastable electronic state produced by irradiation at boiling air temperature with the 514.5 nm line of an Ar+ LASER were obtained for thin (100) single crystal plates in the ranges 4000-430 cm-1 and 4000-550 cm-1 for polarizations along the 1b and c -axes, respectively. The spectra showed that the suggested bending of the FeNO group upon excitation occurs in the (a,b) mirror plane of the ground state crystal. In addition to bands corresponding to Raman lines reported as due to excited nitroprusside, new bands appeared in the infrared spectra. Some of them showed a strong dichroic behavior. On heating the samples some of the new bands disappeared earlier than the bands correspon d ing to the Raman lines. No explanation is still available for those bands.

Study of 5-nitroindazoles' anti-Trypanosoma cruzi mode of action: Electrochemical behaviour and ESR spectroscopic studies

New indazole derivatives have been developed to know about structural requirements for adequate anti-Trypanosoma cruzi activity. In relation to position 1 of indazole ring, we have observed that a butylaminopentyl substituent (14) affords good activity, but N-oxidation of omega-tertiary amino moiety yields completely inactive compounds (17, 18); the substituent at position 3 of indazole ring affects drastically the in vitro activity, 3-OH derivative 13 being completely inactive. On the other hand, since compound 22, denitro-analogue of active compound 4, does not show activity, the 5-nitro substituent of indazole ring seems to be essential. Intramolecular cyclization of side chain at position 1 also affords inactive compounds (19, 20). The electrochemical studies showed that the trypanocidal 5-nitroindazole derivatives yielded nitro-anion radical via one-electron process at physiological pH. This electrochemical behaviour occurs in the parasite according to ESR experiment with the T. cruzi microsomal fraction showing that 5-nitroindazole derivatives suffer bio-reduction without reactive oxygen species generation.

Analgesic and Anti-Inflammatory Activities of Salicylaldehyde 2-Chlorobenzoyl Hydrazone (H2LASSBio-466), Salicylaldehyde 4-Chlorobenzoyl Hydrazone (H2LASSBio-1064) and Their Zinc(II) Complexes

Salicylaldehyde 2-chlorobenzoyl hydrazone (H2LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H2LASSBio-1064) and their complexes [Zn(LASSBio-466)H2O]2 (1) and [Zn(HLASSBio-1064)Cl]2 (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the anti-nociceptive activity was favored in the complex 1. H2LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H2LASSBio-466. H2LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.

Infrared absorption spectra of electronically excited long-lived metastable states in Na2[Ru(CN)5NO]·2H2O

Abstract [Ru(CN)5NO]2− can be excited selectively by two very long-lived electronic metastable states (MSI and MSII) by irradiation at low temperature with blue-near UV light. Upon excitation to MSI and MSII states, CN and NO modes suffer frequency down-shifts, a fact which implies softening of the named bonds. Shifts of vibrational modes of the RuNO group are far larger than shifts of CN modes, a fact that indicates that the metastable states involve electronic transitions mainly located at that group. The MSI and MSII states decay when heating at two different onset temperatures TI T > TI shows that MSII is energetically below MSI.

1,3-Dipolar cycloaddition reactions of azomethine ylides with a cellulose-derived chiral enone. A novel route for organocatalysts development.

Cellulose-derived chiral pyrrolidines were synthesized in excellent yields, regioselectivities, and stereoselectivities via a 1,3-dipolar cycloaddition reaction between levoglucosenone and azomethine ylides. An unprecedented isomerization event led to a new family of pyrrolidines with an unusual relative stereochemistry. Preliminary results showed that these compounds are promising organocatalysts for iminium ion-based asymmetric Diels-Alder reactions.

Structural and spectroscopic characterization of two new Cd(II) complexes: bis(thiosaccharinato)bis(imidazole) cadmium(II) and tris(thiosaccharinato)aquacadmate(II)

Abstract The crystal structures of [Cd(tsac)2(im)2] (1) (tsac=anion of thiosaccharine; im=imidazole) and of (Him)[Cd(tsac)3(H2O)] (2) (Him=imidazolium cation) have been determined at 120 K by single crystal X-ray diffractometry. Complex 1 crystallises in the monoclinic space group P21/a with Z=4 whereas compound 2 is triclinic, space group P(−1) and Z=2. In both compounds, Cd(II) is in a distorted tetrahedral environment. In the neutral complex 1 the metal is coordinated to the S-atom of the two thiosaccharinato ligands and to the N-atom of the imidazole molecules. In the anionic complex 2, Cd(II) is coordinated to three thiosaccharinato S-atoms and to the O-atom of the water molecule. The FTIR spectra of both compounds were also recorded and briefly discussed.

Spectroscopic evidence of vibrational dipole-dipole coupling between nitrosyl groups in some nitroprussides

The nature and magnitude of the intermolecular vibrational coupling between nitrosyl groups in Sr[Fe(CN)5NO]⋅4H2O and Ba[Fe(CN)5NO]⋅2H2O have been studied quantitatively by IR spectroscopy. The isotopic dilution technique has been used by incorporating in the first compound up to 40% of 18O as N18O ligand in the crystal. The results can be interpreted by postulating a dynamic electric dipole–dipole interaction which operates between the polar NO stretching vibrations. The main features of the fine structure displayed by the NO stretching band in the infrared spectra of polycrystalline Sr[Fe(CN)5N(16O/18O)]⋅4H2O, and in single crystals of Ba[Fe(CN)5NO]⋅2H2O can be explained in terms of a linear‐chain model of nitrosyls vibrationally coupled through transition dipole–dipole forces, with interactions between nearest neighbors. The value ‖(∂m/∂S)0‖=13 D/A calculated on the basis of this model for the NO dipole‐moment derivative agrees satisfactorily with the value reported from integrated IR absorption intens...

X-ray diffraction study of copper(I) thiourea complexes formed in sulfate-containing acid ­solutions

The formation of three different copper(I) thiourea complexes in sulfate-containing acid solutions was observed. The ratio between Cu(I) and thiourea (tu) in these complexes depends on the amount of thiourea and copper sulfate in the solution. The crystal and molecular structure of a new complex, [Cu(2)(tu)(6)](SO(4)).H(2)O, was determined, and the formation and structures of [Cu(2)(tu)(5)](SO(4)).3H(2)O and [Cu(4)(tu)(7)](SO(4))(2).H(2)O were confirmed. The compound [Cu(2)(tu)(6)](SO(4)).H(2)O crystallizes in the P1; space group, with a = 11.079 (2), b = 11.262 (1), c = 12.195 (2) A, alpha = 64.84 (1), beta = 76.12 (1), gamma = 66.06 (1) degrees, and Z = 2. The Cu-thiourea complex is arranged as a Cu(I) tetranuclear ion, [Cu(4)(tu)(12)](4+), sited on a crystallographic inversion center. All copper ions are in a tetrahedral coordination with thiourea ligands and located at alternate sites on an eight-membered, crown-like ring.