Armando Marzotto

Dye-sensitized selective photooxidation of methioxine

Abstract The photooxidation, sensitized by rose bengal and methylene blue, of cystine, methionine, histidine, tyrosine, tryptophan and of some related peptides was studied in acid media. Rose bengal in formic acid solution, and methylene blue or rose bengal in aqueous acetic acid solution sensitized a selective oxidation of methionine, which was quantitatively converted to methionine sulphoxide. Irradiation of ribonuclease A (ribonucleate pyrimidinenucleotide-2′-transferase (cyclizing), EC 2.7.7.16) under the same conditions caused the modification of the four methionyl residues and a concomitant 87% decrease of the enzymatic activity, which was correlated to a conformational change of the protein. Chemical reduction of the photooxidized ribonuclease A by thioglycolic acid resulted in the full recovery of the enzymatic activity.

Reversible acetoacetylation of amino groups in proteins

A method is described by which amino groups of proteins such as ribonuclease (ribonucleate pyrimidinonucleotide-2′-transferase (cyclizing), EC 2.7.7.16) and lysozyme (N-acetyl-muramide glycanohydrolase, EC 3.2.1.17) can be acetoacetylated by reaction with diketene. The acetoacetyl group can be removed at 25° from the acetoacetylated enzymes by treatment with hydroxylamine hydrochloride at pH 7. The material thus obtained resembles native proteins in its properties and recovers the full enzymatic activity. The tryptic hydrolysis of acetoacetylated oxidized ribonuclease A has been studied in connection with the investigation of covalent structure in proteins. The lysyl bonds in the protein molecule are rendered resistant to hydrolysis by trypsin while the arginyl bonds are split off.

Synthesis, molecular structure and reactivity of sodium 5-sulfosalicylate dihydrate and sodium[triaqua(5-sulfosalicylato)copper(II)] 2 hemihydrate

Abstract The crystal and molecular structure of sodium 5-sulfosalicylate dihydrate, Na[(H2Ssal)(H2O)2], (1) (H3Ssal=5-sulfosalicylic acid) has been determined through X-ray diffraction analysis. The 5-sulfosalicylate anion has lost the proton at the SO3H group but retains the usual intermolecular hydrogen bond between phenolic and carboxylic oxygen. The reaction in water of 1 with [Cu(II)(H2O)4]SO4·H2O, gives rise to the green sodium[triaqua(5-sulfosalicylato)copper(II)] 2 hemihydrate, Na[(H2O)3(Ssal)Cu(II)]·2×0.5H2O, (2). The 5-sulfosalicylate anion, (Ssal3−), coordinates rather unusually in the syn–syn coordination mode since it binds bidentately the Cu(II) ion through the carboxylic and the phenolic oxygens, with Cu(II)Ocarboxylic=1.909(4) A and Cu(II)Ophenolic=1.885(4) A distances. Copper(II) completes its square-planar coordination with two water molecules and in addition, perpendicularly to the square-planar coordination plane, another two water molecules with long bonds are present (Cu(II)O=2.518 and 2.912 A). The green complex 2 reacts easily with adenine in water at pH 7 giving rise to the violet tetraadeninato(diaqua)-bis(copper(II)) dihydrate, [Cu2(Ade)4(H2O)2])]·2H2O, (3) (Ade−=adeninato monoanion). This complex, that geometrically resembles copper(II) acetate monohydrate, was already described by Sletten. Finally, on the basis of the present results a possible mechanism for the anticancer activity of complex 2 and of other Cu(II)–salicylate complexes is proposed and discussed.

Structure of two polymorphs of the TTF-TCNE charge-transfer complex and the degree of ionicity

Charge-transfer (CT)π complexes between tetrathiafulvalene (TTF, donor) and tetracyanoethylene (TCNE, acceptor) have been studied. Two polymorphs (α and β) were obtained depending on the solvent used. X-Ray analysis has shown that both polymorphs are monoclinic with space group P21/n, are present in dimeric form [(TTF)2(TCNE)2] and possess very similar molecular dimensions. The crystal structure of both polymorphs is composed of mixed stacks of [TTF]2 and [TCNE]2 dimers in a (TTF)2—(TCNE)2—(TTF)2—(TCNE)2 one-dimensional arrangement. The interaction between TTF and TCNE is very strong in both polymorphs, as indicated by the low interplanar spacing (α phase = 3.13 A, β phase = 3.15 A) and low dihedral angle (α phase = 1.26°, β phase = 2.20°) but they differ for the hydrogen-bonding network and lamellar sheets. A method based on the C—S bond lengths provides for these two CT complexes a degree of ionicity or charge transfer (δ) of 0.54 e, in good agreement with that obtained using IR frequencies (δ= 0.5 ± 0.1 e) and very similar to that of TTF–TCNQ (δ= 0.59 e). Nevertheless, in contrast with TTF–TCNQ, these polymorphs exhibit a very high resistivity (≈ 109Ω cm) that may be explained by the dimerization process and by the mixed-stack formation.

Co-ordination chemistry of adenine (HAde): synthesis and characterization of [CuII(tren)(nucleobase)]X2[tren = tris-(2-aminoethyl)amine, X = Cl or NO3] complexes and crystal structure of [CuII(tren)(Ade)]Cl·2H2O

The five-co-ordinate complexes [CuII(tren)(H2O)]Cl21, [CuII(tren)(HAde)]Cl22, [CuII(tren)(HAde)]-[NO3]23 and [CuII(tren)(Ade)]Cl·2H2O 4[tren = tris(2-aminoethyl)amine and HAde = neutral adenine] have been synthesized and characterized. The geometry and structures of the complexes were studied by electronic and IR spectra and, in addition, the structure of complex 4 has been determined by X-ray crystallography. The physicochemical data for complexes 2 and 3 support the presence of neutral adenine co-ordinated to CuII, whereas in complex 4 the adenine molecule is bound in its monoanionic form, as confirmed by the X-ray analysis [monoclinic, space group P21/a, a= 15.001(2), b= 8.422(1), c= 15.039(2)A, β= 105.90(6)°, Z= 4; R= 0.065 for 2596 unique diffraction data]. The co-ordination polyhedron around the Cu2+ ion is approximately trigonal bipyramidal, with the equatorial sites occupied by the three primary amino nitrogen atoms and the axial positions occupied by the tertiary amino nitrogen and the imidazole N9 nitrogen from the adenine monoanion. The Cu–N(9) distance is rather short at 1.965(9)A. Such selective metal bonding in adenine is very probably promoted by the trigonal-bipyramidal geometry around CuII and by the relatively low steric hindrance of the CuII(tren) moiety.

Piperazine (and derivatives) Copper(II) compounds: 1,4-dimethylpiperazin-1,4-ium tetrachlorocuprate(II) and CuN bond formation in trichloro(1-methylpiperazin-1-ium-N4)copper(II) and trichloro(1,4-dimethylpiperazin-1-ium-N4)copper(II).

Abstract The ionic salt (H2Me2ppz)2+ [CuCl4]2− (1), the pseudotetrahedral zwitterionic [CuCl3(HMe2ppz)] (2) and [CuCl3(H2Meppz)] (3) complexes of copper(II) have been synthesized and characterized, [(H2Me2ppz)2+=1,4-dimethyl-piperazin-1,4-ium; (HMe2ppz)+=1,4-dimethylpiperazin-1-ium; (H2Meppz)+=1-methylpiperazin-1-ium]. The X-ray diffraction analysis of compound (1) shows that the [CuCl4]2− anion possesses a flattened tetrahedral geometry with the two largest ClCuCl angles being 125.90(5) and 131.41(5)°. The CuCl distances range from 2.215(1) to 2.267(1) A and all the chlorine atoms are involved in bifurcated hydrogen bonds. Physico-chemical measurements, UV–Vis, IR and especially X-ray analysis, prove that complex 2 is the first example of a Cu(II) ion bonded to one nitrogen atom of the piperazinium ring which is not constrained into a macrocyclic ligand. In fact, the CuCl3 group is coordinated to the (HMe2ppz)+ cation in the unusual axial position similar to the Co(II) derivative. The CuCl3N coordination polyhedron exhibits a pseudotetrahedral geometry with the two largest ClCuCl angles being 132.17(12) and 135.38(7)°. Complex 3 shows the same physico-chemical behaviour as complex 2 confirming that this complex also contains a Cu(II)N bond in a pseudo-tetrahedral environment.

Boat versus chair conformation in N-methyl- and N,N′-dimethylpiperazine platinum(II) complexes studied by X-ray analysis. A rare example of metal chelate piperazine: cis-[PtCl2(Me2ppz)] Part I

Abstract The square-planar platinum(II) complexes [PtCl3(H2Meppz)] (1), trans-[PtCl2(H2Meppz)2]2+2Cl−·2H2O (2), and cis-[PtCl2-(Me2ppz)] (3) (HMeppz=N-methylpiperazine, Me2ppz=N,N′-dimethylpiperazine) have been synthesized and characterized by IR, 1H NMR and X-ray diffraction analysis. In complexes 1 and 2 the hexaatomic ring of N-methylpiperazine adopts a chair conformation with the NCH3 and NPt bonds in equatorial position and the two NH bonds in axial position. The coordination to platinum(II) always occurs through the unmethylated nitrogen atom while the methylated nitrogen is protonated, producing a positive charge on the outside surface of the molecule. In addition, complex 1 is present as an amphilonic species since N+HCH3 is balanced by -PtCl3−. In contrast, in complex 3N,N′-dimethylpiperazine adopts a boat conformation stabilized by chelation of the nitrogen donors to platinum(II) so that complex 3 represents a rare example of piperazine chelated to platinum(II). An attempt is also made to correlate the biological activity of chair and boat piperazine complexes with their structural parameters.

30 Space-group corrections: two examples of false polymorphism and one of incorrect interpretation of the fine details of an IR spectrum

Revised structures are reported for 30 crystalline compounds, based on space groups of higher symmetry than originally reported. In 18 cases the Laue class is revised, in seven cases the center of symmetry is added, in two cases the Laue class change is coupled with the addition of the center of symmetry, in two cases the addition of the center of symmetry also requires the addition of systematic absences and, finally, one case of the addition of systematic absences without changing the Laue group is reported. Two examples (CSD refcodes: DAMLIM and ABPZCU01) of false polymorphism and one (PAVJUR) of the erroneous interpretation of the fine details of IR spectra, owing to incorrect space-group determination, have been detected.

Synthesis and structure of pseudotetrahedral Co(II) zwitterionic complexes: trichloro(1-methylpiperazin-1-ium-N4)cobalt(II) and trichloro(1,4-dimethylpiperazin-1-ium-N4)cobalt(II)

The pseudotetrahedral cobalt(II) zwitterionic complexes, [CoCl3(H2Meppz)] (1) [H2Meppz+=1-methylpiperazin-1-ium cation] and [CoCl3(HMe2ppz)] (2), [HMe2ppz+=1,4-dimethylpiperazin-1-ium cation] have been synthesized and characterized in the solid state by X-ray single crystal analysis, IR spectra, magnetic measurements and electronic spectra. In both the compounds the cobalt(II) center is coordinated in a distorted tetrahedral fashion by the three chloride ions and by one nitrogen of the piperazine ring that retains the more stable chair conformation. The distorted coordination polyhedron in complex 1 preserves the C3v symmetry while in complex 2 it retains only the m symmetry. In complex 1, the (H2Meppz)+ cation binds the Co(II) ion in the equatorial position of the piperazine ring using the unmethylated N1–H nitrogen atom that is less hindered than the methylated one. Complex 2, on the contrary, is a novelty being the first example of a Co(II) ion bound in the axial position of a piperazine ring, this produces a long Co(II)–N bond, 2.108(4) A. Electronic spectra in the solid state are in perfect accordance with the X-ray crystallographic results indicating a C3v symmetry for complex 1 and a Cs(m) symmetry for complex 2. These complexes present strong two-center and three-center hydrogen bonds of N+–H⋯Cl type.

New selective nickel(II)-N3 nitrogen bond in adenine: Synthesis and structure of [(tren) (adenine) (monochloro)nickel(II)] chloride and [(tren)(imidazole)(monoaqua)nickel(II)] dichloride

With the aim to obtain further insight into the nature of the Ni(II)-nitrogen bond in complexes with nucleobases, we have synthesized two novel Ni(II) ternary complexes constituted by Ni(II), tris(2-aminoethyl)amine (tren) and neutral adenine (AdH) or imidazole (ImH). The reaction of NiCl2·6H2O with tren and imidazole yields the ternary [Ni(tren)(ImH)(H2O)]Cl2·H2O complex and the same reaction with adenine instead of imidazole gives the ternary [Ni(tren)(AdH)Cl]Cl complex. The complexes have been studied by spectrophotometric and spectroscopic measurements and by X-ray diffraction. The ternary complex of adenine is monoclinic, space groupC2/c, and exhibits a pseudo-octahedral geometry, being Ni(II) coordinated to the four nitrogen atoms of the tetradentate tren ligand, to a Cl− ion and to the pyrimidine N3 site of a neutral adenine. Such an exclusive Ni-N3 bonding [2.081(4)Å] is now reported for the first time. The ternary complex of imidazole is monoclinic, space groupP21/n. Its pseudo-octahedral geometry is similar to that found in the above adenine complex although a water molecule instead of a Cl− ion is now present in the coordination sphere. In fact, Ni(II) is coordinated to tetradentate tren, to the imidazole N1 nitrogen and to a water molecule. Electronic and1H NMR spectra in solution indicate that the octahedral structures found in the solid state are substantially maintained in solution. Furthermore, the present investigation suggests that the adenine Ni-N3 and imidazole Ni-N1 bonds have the same chemical nature, involving mainly σ- and only partiallyπ-bonding. The Ni-N3 bonding is discussed in connection with biological implications and possible applications.