Nivaldo L. Speziali

N(4)-tolyl-2-benzoylpyridine thiosemicarbazones and their copper(II) complexes with significant antifungal activity: crystal structure of N(4)-para-tolyl-2-benzoylpyridine thiosemicarbazone

) para os complexos. Nossos resultados sugerem que a coordenacao ao cobre constitui estrategia interessante de reducao da dose necessaria a atividade. Three new copper complexes of general formula [Cu(HL)Cl 2 ] have been obtained with N(4)-ortho (H2Bz4oT, HL1), N(4)-meta (H2Bz4mT, HL2) and N(4)-para-tolyl-2-benzoylpyridine thiosemicarbazone (H2Bz4pT, HL3), in which the thiosemicarbazone attaches to the metal through the N py -N-S chelating system. H2Bz4pT (HL3) crystallizes in the P1 – space group, with a = 9.509(3) A, b = 9.807(4) A, c = 11.564(4) A; α = 100.76(2)°, β = 105.99(2)°, γ = 114.59(2)°. The thiosemicarbazones and their copper(II) complexes exhibit high antifungal activities against Candida albicans with low values of minimum inhibitory concentration (MIC), in the 8-0.3 μg mL -1 (23 – 0.7 μmol L -1 ) range for the free bases and in the 1-0.1 μg mL -1 (2 – 0.3 μmol L -1 ) range for the complexes. Our results suggest that coordination to copper(II) could be an interesting strategy for dose reduction.

2-Acetylpyridine thiosemicarbazones: Cytotoxic activity in nanomolar doses against malignant gliomas

2-acetylpyridine N(4)-phenyl thiosemicarbazone (H2Ac4Ph), and its N(4)-ortho-tolyl (H2Ac4oT), N(4)-meta-tolyl (H2Ac4mT), N(4)-para-tolyl (H2Ac4pT), N(4)-ortho-chlorophenyl (H2Ac4oClPh), N(4)-meta-chlorophenyl (H2Ac4mClPh) and N(4)-para-chlorophenyl (H2Ac4pClPh) derivatives were assayed for their cytotoxicity against RT2 (expressing p53 protein) and against T98 (expressing mutant p53 protein) glioma cells. The compounds were highly cytotoxic against RT2 (IC50=24-1.4 nM) and T98 cells (IC50=50-1.0 nM). IC50 for cisplatin=5 (RT2) and 17 μM (T98). The thiosemicarbazones presented haemolytic activity with IC50>10(-3)M, indicating a very good therapeutic index. SAR studies suggested that stereo properties are critical to define the potential activity of the studied compounds against the RT2 cell line, while electronic properties seem to be important for interaction with the biological target in T98 cells.

New Families of Hetero-tri-spin 2p−3d−4f Complexes: Synthesis, Crystal Structures, and Magnetic Properties

In this work we report the synthesis, crystal structures, and magnetic behavior of 2p-3d-4f heterospin systems containing the nitroxide radical 4-azido-2,2,6,6-tetramethylpiperidine-1-oxyl radical (N3tempo). These compounds were synthesized through a one-pot reaction by using [Cu(hfac)2], [Ln(hfac)3] (hfac = hexafluoroacetylacetonate, Ln = Dy(III), Tb(III) or Gd(III)), and the N3tempo radical. Depending on the stoichiometric ratio used, the synthesis leads to penta- or trimetallic compounds, with molecular formulas [Cu3Ln2(hfac)8(OH)4(N3tempo)] (Ln = Gd, Tb, Dy) and [CuLn2(hfac)8(N3tempo)2(H2O)2] (Ln = Gd, Dy). The magnetic properties of all compounds were investigated by direct current (dc) and alternating current (ac) measurements. The ac magnetic susceptibility measurements of Tb(III)- and Dy(III)-containing compounds of both families revealed slow relaxation of the magnetization, with magnetic quantum tunneling in zero field.

Gold(I) complexes with thiosemicarbazones: Cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity

Complexes [Au(H2Ac4DH)Cl]∙MeOH (1) [Au(H(2)2Ac4Me)Cl]Cl (2) [Au(H(2)2Ac4Ph)Cl]Cl∙2H(2)O (3) and [Au(H(2)2Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action.

Organotin(IV) complexes with 2-acetylpyridine benzoyl hydrazones: antimicrobial activity

Reaction of n-butyltin trichloride, [BunSnCl3], and phenyltin trichloride, [PhSnCl3], with 2-acetylpyridine benzoyl hydrazone (H2AcPh), 2-acetylpyridine para-chloro-benzoyl hydrazone (H2AcpClPh) and 2-acetylpyridine para-nitro-benzoyl hydrazone (H2AcpNO2Ph) gave [BunSn(2AcPh)Cl2] (1), [BunSn(2AcpClPh)Cl2] (2), [BunSn(2AcpNO2Ph)Cl2] (3), [PhSn(2AcPh)Cl2] (4), [PhSn(2AcpClPh)Cl2] (5) and [PhSn(2AcpNO2Ph)Cl2] (6) as products. Among the hydrazones H2AcpClPh proved to be the most active against Staphylococcus aureus and Candida albicans. Upon coordination the antibacterial activity of both tin and the hydrazones significantly increases. Complexes 2 and 5 revealed to be the most active as antimicrobial agents.

Pyridine-derived thiosemicarbazones and their tin(IV) complexes with antifungal activity against Candida spp.

[(n-Bu)Sn(2Ac4oClPh)Cl2] (1), [(n-Bu)Sn(2Ac4oFPh)Cl2] (2), [(n-Bu)Sn(2Ac4oNO2Ph)Cl2] (3), [(n-Bu)Sn(2Bz4oClPh)Cl2] (4), [(n-Bu)Sn(2Bz4oFPh)Cl2] (5) and [(n-Bu)Sn(2Bz4oNO2Ph)Cl2] (6) were obtained by reacting [(n-Bu)SnCl3] with 2-acetylpyridine-N4-orthochlorophenyl thiosemicarbazone (H2Ac4oClPh), 2-acetylpyridine-N4-orthofluorphenyl thiosemicarbazone (H2Ac4oFPh), 2-acetylpyridine-N4-orthonitrophenyl thiosemicarbazone (H2Ac4oNO2Ph), and with the corresponding 2-benzoylpyridine-derived thiosemicarbazones (H2Bz4oClPh, H2ABz4oFPh and H2Bz4oNO2Ph). The antifungal activity of the studied compounds was evaluated against several Candida species. Upon coordination of H2Bz4oNO2Ph to tin in complex (6) the antifungal activity increased three times against Candida albicans and Candida krusei and six times against Candida glabrata and Candida parapsilosis. The minimum inhibitory concentration (MIC) values of H2Ac4oNO2Ph and its complex (3) against C. albicans, C. parapsilosis and C. glabrata are similar to that of fluconazole. All studied compounds were more active than fluconazole against C. krusei.

2-Benzoylpyridine-N(4)-tolyl thiosemicarbazones and their palladium(II) complexes: cytotoxicity against leukemia cells.

The palladium(II) complexes [Pd(2Bz4oT)Cl], [Pd(2Bz4mT)Cl], and [Pd(2Bz4pT)Cl] were prepared with N(4)-ortho- (H2Bz4oT) N(4)-meta- (H2Bz4mT) and N(4)-para- (H2Bz4pT) tolyl-thiosemicarbazones derived from 2-benzoylpyridine. The free thiosemicarbazones proved to be highly cytotoxic against Jurkat, HL60 and the resistant HL60.Bcl-X(L) leukemia cell lines at nanomolar concentrations, but were much less cytotoxic to HepG2human hepatoma cells. Upon coordination to palladium(II) the cytotoxic activity against all studied cell lines decreases. However, the high cytotoxicity of the free thiosemicarbazones against leukemia, together with their hepatotoxic profile similar to that of cisplatin suggest that N(4)-tolyl thiosemicarbazones have potential as chemotherapeutic drug candidates.

Structural and spectral studies of thiosemicarbazones derived from 3- and 4-formylpyridine and 3- and 4-acetylpyridine

Abstract Crystal structures of thiosemicarbazones prepared from 3- and 4-formylpyridine and 3- and 4-acetylpyridine are included along with their UV spectra. 4-Formylpyridine thiosemicarbazone has the following structural properties: monoclinic, P21/n, a=7.2420(5), b=13.961(1), c=8.415(1) A , β=90.90(1)°, V=850.7(1) A 3 and Z=4; for 3-formylpyridine thiosemicarbazone: monoclinic, C2/c, a=13.661(2), b=7.1120(4), c=19.046(2) A , β=107.71(1)°, V=1762.8(3) A 3 and Z=8; for 4-acetylpyridine thiosemicarbazone: triclinic, P-1, a=8.104(3), b=8.512(2), c=8.708(3) A , α=83.85(0), β=66.66(0), γ=62.87(0)°, V=488.9(3) A 3 and Z=2; for 3-acetylpyridine thiosemicarbazone monoclinic, P21/a, a=8.408(1), b=11.853(2),= c=9.777(3) A , β=97.66(2)°, V=985.7(4) A 3 and Z=4. Intramolecular and intermolecular hydrogen bonding are both present. There is a difference in the angles between the mean planes of the pyridine ring and thiosemicarbazone moiety in the two series.

Role of the Substituent Effect over the Squarate Oxocarbonic Ring: Spectroscopy, Crystal Structure, and Density Functional Theory Calculations of 1,2-Dianilinosquairane

This work presents the crystal structure and the investigation under a supramolecular perspective of a squaric acid derivative obtained from the replacement of the hydroxyl groups by anilines. The squaraine obtained (1,2-dianilinesquaraine) crystallizes in the Pbcn space group, in a unit cell with a = 26.5911(8) Å, b = 6.1445(10) Å, and c = 7.5515(5) Å. The bond lengths in the oxocarbon ring, squarate-N and C−O bonds present the character of double bonds. Also the difference between the longer and shorter C-C bond in the four-membered ring (ΔCC) is 0.0667 Å, showing a good degree of equalization of these bond lengths. The phenyl rings are slightly distorted in relation to the squarate ring, and the angle measured between the best plane fitted in each ring is 37.2(9)°. Each molecule is connected to the other through a hydrogen bond involving the N-H···O moieties, where the donor···acceptor distance is 2.826(1) Å, forming ribbons in a unidimensional arrangement C(5)R22(10) along the b axis. These structures are mutually connected by π-stacking interactions extending the supramolecular structure in a two-dimensional fashion. Besides, an interesting crossed structure can be easily identified in the formed sheets that are built through the C-H/π interactions. DFT calculations at the B3LYP/6-311++G(d,p) level of theory show an approximately planar molecular structure for the isolated molecule. However, when a dimer model built from hydrogen bonds is considered, the optimized structure presents considerable torsion between the phenyl and squarate rings, as observed in the experimental data. The electronic spectrum shows a strong absorption band at 341 nm that is red-shifted compared to the squarate maximum absorption (290 nm), indicating a more effective electronic delocalization. The most characteristic vibrational modes of the oxocarbon species were used as spectroscopic probe to understand how the substituent groups affect the oxocarbon moiety and, consequently, the vibrational spectra. The analysis shows that the modes associated with the C-Cox bonds are the most affected. Also the character of the double bond of squarate-N and the single bond for the phenyl-N are easily identified. In a general form, the calculated vibrational modes of the dimer model were in better accordance with the experimental data, mainly when the mode has a contribution from the acceptor molecule in the intermolecular interaction.

Synthesis of a polymetallic Pt, Sn complex containing square planar and trigonal bipyramidal platinum centres: Crystal and molecular structure of bis{chlorotriethylphosphinoplatinum(II)}μ-2,3,5,6-tetrakis(α-pyridyl)pyrazinetetrakis(trichlorostannyl)triethylphosphinoplatinate(II)

Abstract Reaction between 2,3,5,6-tetrakis(α-pyridyl)pyrazine (TPP) and the dimer [Pt2(PEt3)2Cl4] yielded an ionic complex of formula [{Pt(PEt3)Cl}2μ-(TPP)][Pt(PEt3)Cl3]2 (1), in which TPP behaves as a bis(bidentate) ligand between the two Pt atoms of the cation. Insertion of SnCl2 into the Pt–Cl bonds of this compound led to an unusual rearranged product, [{Pt(PEt3)Cl}2μ-(TPP)][Pt(SnCl3)4(PEt3)] (2), with a rare example of a pentacoordinate Pt(II) species in the anionic moiety, where Pt is at the centre of a trigonal bipyramid, in addition to two other square planar Pt atoms in the cationic moiety.