The possible role of 94-125 peptide fragment of histone H2B in nickel-induced carcinogenesis.

The molecular mechanism by which nickel carcinogenicity is exerted is not fully understood. However, it is believed to involve DNA damage and epigenetic effects in chromatin, resulting from metal binding to the cell nucleus. Histone nuclear proteins are the major candidates for metal binding not only due to their abundance but also due to the presence of strong binding sites within their sequence. In order to investigate the binding capacity of histone H2B toward Ni(2+) ions, we synthesized the peptide Ac-IQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK-Am (H2B(94-125)) as a model of the C-terminal tail. Complexation of H2B(94-125) with Ni(2+) starts at pH around 5 with the formation of a distorted octahedral complex. Over pH 8, this species shifts to a square-planar geometry, with the complete consumption of free Ni(2+) ions at pH 10. The formation of the diamagnetic square-planar complex was further studied by means of NMR spectroscopy. On the basis of the NOE connectivities we determined a well-resolved solution structure for the binding site of the H2B(94-125)-Ni(2+) complex, including residues E(12)LAKHAVS(19). Interestingly, nickel binding strongly affects the C-terminal of the peptide, forcing it to approach the coordination plane. If such a structural alteration is able to occur under physiological conditions, it is highly possible that it interferes with the histone's physiological role and particularly with the ubiquitination process, taking place at Lys(120). We believe that these findings will assist in a better understanding of the role of histone H2B in the mechanisms of metal-induced toxicity and carcinogenesis.

New antimony(III) bromide complexes with thioamides: synthesis, characterization, and cytostatic properties.

New antimony(III) bromide complexes with the heterocyclic thioamides, thiourea (TU), 2-mercapto-1-methylimidazole (MMI), 2-mercapto-benzimidazole (MBZIM), 2-mercapto-5-methyl-benzimidazole (MMBZIM), 5-ethoxy-2-mercapto-benzimidazole (EtMBZIM), 2-mercapto-3,4,5,6-tetrahydro-pyrimidine (tHPMT), 2-mercaptopyridine (PYT), 2-mercapto-thiazolidine (MTZD), 3-methyl-2-mercaptobenzothiazole (MMBZT), and 2-mercaptopyrimidine (PMTH) of formulas [SbBr(3)(TU)(2)] (1), [SbBr(3)(MMI)(2)] (2), {[SbBr(2)(MBZIM)(4)](+) [Br](-) H(2)O} (3), {[SbBr(2)(mu(2)-Br)(MMBZIM)(2)](2)} (4), {[SbBr(2)(mu(2)-Br)(EtMBZIM)(2)](2) MeOH} (5), {[SbBr(3)(mu(2)-S-tHPMT)(tHPMT)](n)} (6), {[SbBr(2)(mu(2)-Br)(PYT)(2))(n)} (7), {[SbBr(2)(mu(2)-Br)(MTZD)(2)](n)} (8), [SbBr(3)(MMBZT)(2)] (9), and {[SbBr(5)](2-)[(PMTH(2)(+))(2)]} (10) have been synthesized and characterized by elemental analysis, conductivity measurements, FTIR spectroscopy, FT-Raman spectroscopy, TG-DTA analysis, and X-ray powder diffraction. The crystal structures of 3, 4, 5, 6, 7, 8, and 10 were also determined by X-ray diffraction. In 3, four sulfur atoms from thione ligands and two bromide ions form an octahedral (O(h)) cationic [SbS(4)Br(2)](+) species in which the two bromide anions lie at axial positions. A third bromide counteranion neutralizes the whole complex. 4 and 5 are dimers, whereas 6, 7 and 8 are polymers, built up by monomeric units of square pyramidal (SP) geometry around the metal center, which were formed by two sulfur atoms of thioamide ligands and three bromide ions. Finally, 10 is ionic salt containing 1D polymeric network of {[SbBr(5)](2-)}(n) anions and (-)[(PMTH(2)(+))2] counter cations in the lattice. The complexes showed mostly a moderate cytostatic activity against a variety of tumor cell lines.

Synthesis, characterization, and biological studies of organotin(IV) derivatives with o- or p-hydroxybenzoic acids.

Organotin(IV) complexes with o- or p-hydroxybenzoic acids (o-H(2)BZA or p-H(2)BZA) of formulae [R(2)Sn(HL)(2)] (where H(2)L = o-H(2)BZA and R = Me- (1), n-Bu- (2)); [R(3)Sn(HL)] (where H(2)L = o-H(2)BZA and R = n-Bu- (3), Ph- (4) or H(2)L = p-H(2)BZA and R = n-Bu- (5), Ph- (6)) were synthesized by reacting a methanolic solution of di- and triorganotin(IV) compounds with an aqueous solution of the ligand (o-H(2)BZA or p-H(2)BZA) containing equimolar amounts of potassium hydroxide. The complexes were characterized by elemental analysis, FT-IR, Far-IR, TGA-DTA, FT-Raman, Mössbauer spectroscopy, (1)H, (119)Sn-NMR, UV/Vis spectroscopy, and Mass spectroscopy. The X-ray crystal structures of complexes 1 and 2 have also been determined. Finally, the influence of these complexes 1-6 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically studied and the results showed that triorganotin(IV) complex 6 has the lowest IC(50) value. Also complexes 1-6 were studied for their in vitro cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, and the results showed that the complexes have high activity against these cell lines with triphenyltin((IV) complex 4 to be the most active one.

Anti-proliferative and antitumor activity of organotin(IV) compounds. An overview of the last decade and future perspectives.

Organotins(IV) exhibit significant in vitro anti-proliferative activity, while the in vivo tests are encouraging. The recent reports on the anti-proliferative activity of organotin(IV) compounds are summarized in this review. The period covered by this work goes back to 2009 until late 2018, while the earlier ones, are included over the previous review of our group published by S.K. Hadjikakou, N. Hadjiliadis, in Coord Chem Rev, 253 (2009) 235-249. During the last decade (2009-2018), >300 organotin(IV) derivatives with oxygen-donor ligands, such as carboxylic acids, amino-acids, Non Steroidal Anti-inflammatory Drugs (NSAIDs), biological active derivatives or natural products, organotins(IV) with sulfur containing ligands such as thiones, thiosemicarbazones, dithiocarbamates, organotin(IV) compounds of oximes and organotins(IV) with amines or semicarbazones were screened for their anti-proliferative effect against various cancer cell lines and their results are included in numerous reports over this period. Although much work has been carried out on organotin(IV) derivatives with O-donor ligands, however significant fewer reports are found on organotins(IV) with oximes as ligands.

Biological studies of new organotin(IV) complexes of thioamide ligands.

New organotin(IV) complexes with heterocyclic thioamides 2-mercapto-benzothiazole (Hmbzt), 5-chloro-2-mercapto-benzothiazole (Hcmbzt) and 2-mercapto-benzoxazole (Hmbzo) of formulae [(C(6)H(5))(3)Sn(mbzt)] (1), [(C(6)H(5))(3)Sn(cmbzt)] (3) and [(C(6)H(5))(2)Sn(cmbzt)(2)] (4), together with the already known [(C(6)H(5))(3)Sn(mbzo)] (2), [(n-C(4)H(9))(2)Sn(cmbzt)(2)] (5) and [(CH(3))(2)Sn(cmbzt)(2)] (6) were used to study their influence on the peroxidation of oleic acid. The influence of complexes (3)-(6) upon peroxidation of oleic acid showed that the formation of reactive radicals caused the initiation of the chain radical oxidation of the substrate. The influence of complexes (1)-(6) upon the catalytic peroxidation of linoleic acid by the enzyme lipoxygenase (LOX) was also studied and compared to those of cisplatin. Compounds (1)-(6) were finally tested for in vitro cytotoxicity against leiomyosarcoma cells.

Synthesis, characterization and DNA binding properties of oligopyridine-ruthenium(II)-amino acid conjugates.

The DNA-binding properties of a number of ruthenium oligopyridine complexes with conjugated amino acids having the general formulae [Ru(terpy)(4-COY-4'-Mebpy)(X)](n)(+), X=NO (n=3), X=Cl (n=1) and NO(2) (n=1) and Y=AlaCONH(2) and TrpCONH(2) are reported. The new complexes were spectroscopically characterized and their DNA-binding properties were studied by means of circular dichroism (CD), (23)Na and (31)P NMR spectroscopy. The results show that the chlorido complexes interact by coordination to the DNA bases with the conjugated amino acid able to provide an additional interaction with the DNA helix. In addition, electrostatic interactions between all studied complexes and the DNA polyanion were observed. The nitro complexes were found to be insignificant, affecting only the (31)P NMR signal, probably due to changes in the hydration sphere of the DNA close to the phosphates.

An NMR study of the interaction between the human copper(I) chaperone and the second and fifth metal-binding domains of the Menkes protein.

The interaction between the human copper(I) chaperone, HAH1, and one of its two physiological partners, the Menkes disease protein (ATP7A), was investigated in solution using heteronuclear NMR. The study was carried out through titrations involving HAH1 and either the second or the fifth soluble domains of ATP7A (MNK2 and MNK5, respectively), in the presence of copper(I). The copper-transfer properties of MNK2 and MNK5 are similar, and differ significantly from those previously observed for the yeast homologous system. In particular, no stable adduct is formed between either of the MNK domains and HAH1. The copper(I) transfer reaction is slow on the time scale of the NMR chemical shift, and the equilibrium is significantly shifted towards the formation of copper(I)-MNK2/MNK5. The solution structures of both apo- and copper(I)-MNK5, which were not available, are also reported. The results are discussed in comparison with the data available in the literature for the interaction between HAH1 and its partners from other spectroscopic techniques.

Interpenetrated networks from a novel nanometer-sized pseudopeptidic ligand, bridging water, and transition metal ions with cds topology.

The combination of a new pseudopeptidic ligand, transition metal ions, and bridging water molecules results in the formation of [M(mu-TBG)(mu-H2O)(H2O)2].2H2O (M: Cu, Co and H2TBG: terephthaloylbisglycine); both compounds show rare two-fold interpenetrated three-dimensional cds-nets and reversible loss of coordinated and lattice water molecules.

Synthesis and characterization of the diastereomers Lambda- and Delta-[Ru(bpy)2(m-bpy-L-Arg-Gly-L-Asn-L-Ala-L-His-L-Glu-L-Arg)]Cl2 1H NMR studies on their interactions with the deoxynucleotide duplex d[(5'-GCGCTTAAGCGC-3')2] and d[(5'-CGCGATCGCG-3')2].

The diastereomeric complexes Lambda- and Delta-[Ru(bpy)(2)(m-bpy-7p)]Cl(2), (bpy=2,2'-bipyridine, m-bpy-7p=4-methyl-4'-Arg-Gly-Asn-Ala-His-Glu-Arg-CONH(2)-2,2'-bipyridine) were synthesized and characterized and their binding properties to the deoxynucleotide duplexes d(5'-CGCGATCGCG-3')(2) and d(5'-GCGCTTAAGCGC-3')(2) were studied by means of (1)H NMR spectroscopy. 7p is part of the recognition loop of the restriction endonuclease MunI, a type II restriction enzyme from Mycoplasma unidentified which recognizes the palindromic hexanucleotide sequence C/AATTG and cleaves it as indicated by the slash. The Delta-isomer binds to the terminal CG/GC major groove of d(CGCGATCGCG)(2) decanucleotide, whereas the Lambda-isomer approaches the GCT/CGA sequence. On the other hand, weak binding of the Delta-isomer to the end of d(GCGCTTAAGCGC)(2) into two different orientations is observed. In the case of the Lambda-isomer, the bpy ligand(s) are located into the major groove of the central TT/AA sequence. The role of appended peptide sequences in sequence selectivity binding to DNA is being addressed.

An extremely stable Ni(II) complex derived from the hydrolytic cleavage of the C-terminal tail of histone H2A.

The C-terminal blocked tetrapeptides SHHK- and SAHK-, which represent the fragments produced from the hydrolysis of the hexapeptides' -TASHHK-, -TESHHK-, and -TESAHK- complexes with Ni(II), were synthesized and their interactions with Ni(II) ions were studied potentiometrically and spectroscopically. Both tetrapeptides interact strongly with Ni(II) ions leading to square-planar complexes with 4N {NH(2),2N(-),N(im)} coordination. The stability of the Ni-SHHK- complex is about 2 orders of magnitude higher than the Ni-SAHK- complex. Spectroscopic evidence and theoretical predictions suggest the positioning of the free imidazole ring, in the Ni-SHHK- complex, above the coordination plane, explaining the extra stability of the complex.

Design and Synthesis of New Biomimetic Materials by Sol-Gel: A Cu(II)(histidine)(2) Complex Covalently Bonded on a Silica Matrix.

The synthesis of a new histidine-silane derivative, Boc-His(Boc)-CONH-(CH(2))(3)Si(OEt)(3), is reported. Hydrolysis and co-condensation of this monomer with tetraethoxysilane, via the sol-gel procedure, results in a hybrid inorganic-organic material that bears histidine molecules covalently bonded on a silica matrix. 1D-ESEEM and 2D-HYSCORE studies of its Cu(II) complex show that the copper atom is coordinated by two inequivalent histidine imidazoles. The new Cu(II) material exhibits catalytic activity for DTBQ formation in the presence of dioxygen, with considerable turnover rates and yields. In addition it is highly recyclable and shows high specific surface area.

Transition-Metal Derivatives of a Functionalized Cyclopentadienyl Ligand. 15. Synthesis and Structures of Amino Cyclopentadienyl Derivatives of Rhodium(I) and Rhodium(III) Including Water-Soluble Compounds.

The synthesis of monometallic rhodium(III) and rhodium(I) derivatives of dialkylamino-functionalized cyclopentadienyl using the corresponding cyclopentadiene as starting material is facilitated by the presence of the basic amino group. This procedure affords the chloro salts of the substituted rhodicinium cation [(eta(5)-C(5)H(4)(CH(2))(2)NMe(2)H)(2)Rh(III)](3+) ([1][Cl](3)) from the reaction of the [2-(dimethylamino)ethyl]cyclopentadiene with Na(3)Rh(III)Cl(6). 12H(2)O. Similarly the cationic half-sandwich complexes [(eta(5)-C(5)H(4)(CH(2))(n)()NMe(2)H)Rh(I)(cod)](+) (n = 2, [2][Cl], n = 3, [5][Cl]) are obtained from the reaction of the corresponding dialkylamino cyclopentadiene with [RhCl(cod)](2). These types of cationic complexes, 1, 2, and 5, bear pendant ammonium groups. The most classical procedure, starting from the lithium or more efficiently from the sodium cyclopentadienide salt, was used to synthesize neutral complexes [(eta(5)-C(5)H(4)(CH(2))(n)()NMe(2))Rh(I)(cod)] (n = 2, 3; n = 3, 4). The structure of the chloride bis(hexafluorophosphate) salt, [(eta(5)-C(5)H(4)(CH(2))(2)NMe(2)H)(2)Rh(III)](3+)(Cl(-))(PF(6)(-))(2), ([1][Cl][PF(6)](2)) was solved in the triclinic space group P&onemacr; with one molecule in the unit cell, the dimensions of which are a = 6.617(2) Å, b= 7.436(2) Å, c = 13.965(3) Å, alpha = 76.39(2) degrees, beta = 82.31(3) degrees, gamma = 87.26(2) degrees, and V = 661.8(3) Å(3). The noncentrosymmetric character of this solid is attributed to the chloride ion. The tetrafluoroborate salt [(eta(5)-C(5)H(4)(CH(2))(2)NMe(2)H)Rh(I)(cod)](+)(BF(4)(-)) ([2][BF(4)]) crystallizes in the tetragonal space group P4(2)/n with eight molecules in the unit cell, the dimensions of which are a= 21.183(2) Å, b = 21.179(3) Å, c= 8.324(2) Å, and V = 3734(1) Å(3). Least squares refinement leads to values for the conventional R index of [1][Cl][PF(6)](2) (0.0484 for 2191 reflections used) and of [2][BF(4)] (0.0525 for 1083 reflections used); in both cases I > 3sigma(I). As expected, compounds like [2][Cl](3,) [1][Cl][PF(6)](2), [2][Cl], [2][BF(4)], [5][Cl], and [5][BF(4)] are soluble in water.

Complexes of Zn(2+), Cd(2+), and Hg(2+) with 2-(alpha-Hydroxybenzyl)thiamine Monophosphate Chloride.

The binding sites of Zn(2+), Cd(2+), and Hg(2+) in complexes with 2-(alpha-hydroxybenzyl)thiamine monophosphate chloride, (LH)(+)Cl(-), have been investigated in the solid state [2-(alpha-hydroxybenzyl)thiamin monophosphate chloride monoprotonated at the phosphate group and protonated at N(1)' is denoted as (LH)(+)Cl(-); therefore, the ligand monoprotonated at the phosphate group and deprotonated at N(1)' is L]. Complexes of formulae MLCl(2), M(LH)Cl(3), and (MCl(4))(2)(-)(LH)(2)(+) (M = Zn(2+), Cd(2+), and Hg(2+)) were isolated in aqueous and methanolic solutions, depending on pH. The crystal structure of the complex of formula HgL(2)Cl(2) was solved, together with that of the free ligand (LH)(+)Cl(-), by X-ray crystallography. HgL(2)Cl(2) crystallizes in C2/c, with a = 32.968(6) Å, b = 7.477(2) Å, c = 21.471(4) Å, beta = 118.19(1) degrees, V = 4665(2) Å(3), and Z = 4. (LH)(+)Cl(-) crystallizes in Cc, with a = 10.951(3) Å, b = 17.579(4) Å, c = 13.373(3) Å, beta = 105.36(2) degrees, V = 2482.4(10) Å(3), and Z = 4. Mercury(II) binds to the N(1') of the pyrimidine ring. Both ligands are in the S conformation [Phi(T) = -98.1(9) degrees and Phi(P) = 176.1(10) degrees for HgL(2)Cl(2) and Phi(T) = 104.1(5) degrees and Phi(P) = 171.9(6) degrees for (LH)(+)Cl(-)]. (31)P and (13)C NMR spectra, together with vibrational spectra (IR/Raman), are used to deduce the binding sites of the metal and the protonation states of the ligand at various pH values. It is found that solid-state (31)P NMR spectroscopy is particularly useful in characterizing these complexes as the (31)P shielding tensors are sensitive to the state of the phosphate group. On the other hand, the (31)P NMR spectra indicate that direct bonding between Zn(2+) and Cd(2+) to the phosphate can occur under certain preparation conditions. Solid-state (13)C NMR and vibrational (IR/Raman) spectroscopic results are also in agreement with the other techniques.

Copper(I) interaction with model peptides of WD6 and TM6 domains of Wilson ATPase: regulatory and mechanistic implications.

With the aim to investigate the mechanism of Cu(I) transport by Wilson ATPase (ATP7B), we have studied the interaction of the peptides 2K10p (CH(3)CO-Lys-Gly-Met-Thr-Cys-Ala-Ser-Cys-Val-His-Asn-Lys-CONH(2)), and 2K8p (CH(3)CO-Lys-Leu-Cys-Ile-Ala-Cys-Pro-Cys-Ser-Lys-CONH(2)), part of the sixth metal binding domain (WD6) and the sixth transmembrane segment (TM6) of Wilson ATPase, respectively, by means of CD, NMR spectroscopy and homology modeling. In addition, the interaction of Cu(I) with the 2K8p mutants 1s (CH(3)CO-Lys-Leu-Ser-Ile-Ala-Cys-Pro-Cys-Ser-Lys-CONH(2)), 2s (CH(3)CO-Lys-Leu-Cys-Ile-Ala-Ser-Pro-Cys-Ser-Lys-CONH(2)) and 3s (CH(3)CO-Lys-Leu-Cys-Ile-Ala-Cys-Pro-Ser-Ser-Lys-CONH(2)), containing two cysteines in various positions, have been studied with the same methods, in order to understand the role of each cysteine in copper binding. Our studies show that the three cysteine thiolates present in the 2K8p peptide sequence act mainly as bridging ligands for Cu(I) binding, and dithiothreitol acts as an important ligand in Cu(I) ligation by 2K10p and the 2K8p mutants. Formation of oligomeric species has been evidenced for all peptides except 2s. Shift of the equilibrium between the various oligomeric species has been accomplished by reducing the Cu(I):peptide ratio. Significant shifts of proline protons upon interaction with Cu(I) have been observed for all proline containing peptides implying a possible role of proline in facilitating Cu(I) binding. These findings have been further discussed with respect to the molecular basis of copper trafficking and intermolecular interactions.

Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac-HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD.

Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac-HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD were studied by potentiometric and spectroscopic (UV-Vis, CD and EPR) techniques. The results reveal that both ligands have effective metal binding sites, but the tripeptide is a much stronger complexing agent than the tetrapeptide. The formation of a macrochelate via the coordination of the imidazolyl residues is suggested in the copper(II)-Ac-HisValHis-NH2 system in the acidic pH range, while a 4N complex predominates at physiological pH. The interaction of Ac-HisValHis-NH2 with zinc(II) results in the formation of a precipitate indicating polynuclear complex formation. Both copper(II)-Ac-HisValHis-NH2 and copper(II)-HisValHis systems exhibit catalytic activity toward the dismutation of superoxide anion at physiological pH, but the saturated coordination sphere of the metal ions in both systems results in low reactivity as compared to the native enzyme.

Enantioselective binding of lambda- and delta-[Ru(bpy)(2)(HPIP)]Cl2 (HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline) to the hexanucleotide [d(5'-GTCGAC-3')2].

Multidimensional NMR techniques (1D (1)HNMR, 2D DQF (1)H(1)H COSY and 2D (1)H(1)H NOESY), electrospray ionization mass spectrometry (ESI-MS) and electronic spectroscopy, were performed to study the interactions of the enantiomers lambda- and delta-[Ru(bpy)(2)(HPIP)]Cl(2), (HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthro-line) with the self complementary hexanucleotide duplex d(5'-GTCGAC-3')(2). The results show that the delta-[Ru(bpy)(2)(HPIP)]Cl(2) binds tightly to the oligonucleotide, by intercalation of the ligand HPIP, between the A5 and C6 base sequence of the same strand, probably through the minor groove. Lambda-enantiomer binds weakly, suggesting groove interactions with the hexanucleotide duplex. ESI-MS spectrometry and UV-vis spectroscopy also confirmed these observations.

Synthesis, structural characterization and in vitro cytotoxicity of organotin(IV) derivatives of heterocyclic thioamides, 2-mercaptobenzothiazole, 5-chloro-2-mercaptobenzothiazole, 3-methyl-2-mercaptobenzothiazole and 2-mercaptonicotinic acid.

Five new organotin(IV) molecules with the heterocyclic thioamides; 2-mercaptobenzothiazole (Hmbzt), 5-chloro-2-mercaptobenzothiazole (Hcmbzt), 3-methyl-2-mercaptobenzothiazole (mmbzt) and 2-mercaptonicotinic acid (H(2)mna) of formulae [(n-C(4)H(9))(2)Sn(mbzt)(2)] (1), [(C(6)H(5))(2)Sn(mbzt)(2)] (2), [(CH(3))(2)Sn(cmbzt)(2)].1.7(H(2)O)] (3), [(n-C(4)H(9))(2)SnCl(2)(mmbzt)(2).(CH(2)Cl(2))] (4) and [[(C(6)H(5))(3)Sn](2)(mna).[(CH(3))(2)CO]] (5) have been synthesized and characterized by elemental analysis, 1H-, 13C-NMR, FT-IR and Mössbauer spectroscopic techniques. Crystal structures of molecules 1, 3 and 5 have been determined by X-ray diffraction at 173(1) K (1 and 5) and 293(2) K (3). Compound 1 C(22)H(26)N(2)S(4)Sn, is monoclinic, space group C2/c, a=44.018(2), b=8.8864(5), c=12.8633(7) A, beta=104.195(5) degrees, Z=8. Compound 3 is also monoclinic, space group P2(1)/c and a=17.128(2) A, b=17.919(2) A, c=7.3580(10) A, beta=98.290(10) degrees, Z=4. In both molecules 1 and 3, two carbon atoms from aryl groups, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(IV) with trans-C(2), cis-N(2), cis-S(2) configurations. Compound 5 C(45)H(39)NO(3)SSn(2) is monoclinic, space group P2(1)/n, a=9.1148(2) A, b=29.2819(6), c=15.5556(4) A, beta=106.2851(9) degrees, Z=4. Complex 5 contains two [(C(6)H(5))(3)Sn(IV)] moieties linked by a double deprotonated 2-mercaptonicotinic acid (H(2)mna). Both tin(IV) ions are five coordinated. This complex is the an example of a pentacoordinated Ph(3)SnXY system with an axial-equatorial arrangement of the phenyl groups at Sn(1) atom. Compounds 1, 3 and 5 were tested for in vitro cytotoxicity against the cancer cell line of sarcoma cells (mesenchymal tissue) from the Wistar rat, polycyclic aromatic hydrocarbons (benzo[a]pyrene) carcinogenesis. Compound 5 exhibits strong cytotoxic activity, while complexes 1 and 3 show less cytotoxic activity.

High-pressure Fourier transform micro-Raman spectroscopic investigation of diiodine-heterocyclic thioamide adducts.

The pressure dependences of the Fourier transform micro-Raman spectra of four heterocyclic thioamides [[(bztzdtH)I2] x I2] (1) (bztzdtH = benzothiazole-2-thione), [(bztzdtH)I2] (2), [[(tzdtH)2I+] x I3- x 2I2] (3) (tzdtH = thiazoline-2-thione), and [[(bzimtH)I2]2 x I2 x 2H2O] (4) (bzimtH = benzimidazole-2-thione) have been studied between ambient pressure and 50 kbar. For 1, generation of I3- ions through disproportionation reactions is evident as the pressure is increased. There are empirical linear correlations between the frequency and (I-I) bond length and the applied pressure. The iodine adduct of thioamide 2 is more sensitive to pressure when compared to the 1 or 4 iodine adducts. This difference in behavior may be attributed to differences in crystal structures or to a lower I-I bond order. Monitoring of other vibrational transitions of the thiomide structure reveals several less important pressure dependences.

Copper effective binding with 32-62 and 94-125 peptide fragments of histone H2B.

In an attempt to investigate the role of histone H2B in Cu(II) induced toxicity and carcinogenesis, we synthesized the terminally blocked peptides H2B(32-62) (SRKESYSVYVYKVLKQVH(48)PDTGISSKAMGIM) and Η2Β(94-125) (IQTAVRLLLPGELAKH(110)AVSEGTKAVTKYTSS), mimicking the N-terminal histone-fold domain and C-terminal tail of histone H2B, respectively and studied their interaction with Cu(II) ions by means of potentiometric titrations and spectroscopic techniques (UV-visible, CD and EPR). Both peptides, H2B(32-62) and H2B(94-125), interacted efficiently with Cu(II) ions, forming several species from pH 4 to 11, with His(48) and His(110) serving as anchors for metal binding. In H2B(32-62), the effective Cu(II) binding is emphasized by the formation of a soluble Cu(II)-H2B(32-62) complex, unlike the unbound peptide that precipitated over pH 7.9. At physiological pH, both peptides form tetragonal 3N species with a {N(Im), 2N(-)} coordination mode. At this pH, H2B(32-62) presented the formation of coordination isomers, differentiated by the presence in one of them, of an axial coordination of the carboxylate group of Asp(50). Copper binding with both H2B(32-62) and H2B(94-125) may induce a conformational change in the peptides' original structure. At physiological conditions, this effect may interfere with nucleosome's structure and dynamics, including the ubiquitination of Lys(120) which is linked to gene silencing.

DNA strand breakage induced by CuII and NiII, in the presence of peptide models of histone H2B.

In the present study we used the plasmid relaxation assay, a very sensitive method for detection of DNA strand breaks in vitro, in order to evaluate the role of peptide fragments of histone H2B in DNA strand breakage induced by copper and nickel. We have found that in the presence of peptides modeling the histone fold domain (H2B(32-62) and H2B(63-93)) as well as the N-terminal tail (H2B(1-31)) of histone H2B there is an increased DNA damage by Cu(2+)/H(2)O(2) and Ni(2+)/H(2)O(2) reaction mixtures. On the contrary, the C-terminal tail (H2B(94-125)) seems to have a protective role on the attack of ROS species to DNA. We have rendered our findings to the interactions of the peptides with DNA, as well as with the metal.