Marino Nicolini

Aluminum(III) influences the permeability of the blood-brain barrier to [14C]sucrose in rats

To determine the influence of the metal coordination sphere on the permeability of the blood-brain barrier (BBB), rats were injected intraperitoneally with aluminum lactate (Al(lact)3), aluminum acetylacetonate (Al(acac)3), aluminum maltolate (Al(malt)3) at pH 7.5, or with physiological saline. Two h after each treatment, [14C]sucrose physiological saline solution was injected in animals, and the radioactivity was measured in 5 brain regions (cerebral cortex, mesencephalon, diencephalon, medulla-pons, cerebellum). Radioactivity was significantly elevated in brains from animals treated with Al(malt)3 (hydrolytically stable and hydrophilic), and with Al(acac)3 (hydrolytically stable and lipophilic) but not with Al(lact)3. Time-course study carried out at 2, 4 and 24 h with different aluminum compounds showed a persistent radioactivity 24 h after treatment only in the brain from animals treated with Al(acac)3. Morin stain localized AlIII only in neurons from animals treated with Al(acac)3. These findings indicate that AlIII alters the BBB function in the rat either permanently or transiently depending on the physiochemical properties of the metal coordination sphere. Implications of these results, in terms of AlIII as a potential toxic factor in humans, are considered and discussed.

Rhenium(V) oxo complexes with schiff base ligands containing four or five coordination sites. X-ray molecular structure of [N,N′-3-azapentane-1,5-diylbis(salicylideneiminato)(3-)-O,O′,N,N′,N″]oxorhenium(V)

Abstract The reactions of [ReOCl4]− with Schiff base ligands derived from salicylaldehyde and 1,5-diamino- pentane (H2L1a), -hexane (H2L1b), -heptane (H2L1c) or diethylentriamine (H3L2) have been investigated. The complexes ReOCl2(EtOH)HL1n (I) (n=a, b or c), Re2O2(MeOH)2Cl4HL2 (II), ReOClL1n (III) and ReOL2 (IV), have been synthesized and characterized with the usual physicochemical measurements. The crystal structure of ReOL2 was determined by single crystal X-ray methods. Crystals are monoclinic, space group P21/c, with a=9.470(7), b=9.358(8), c=21.859(12) A, β=99.23(8)16° and Z=4. X-ray diffraction provides 5601 observed reflections (up to 2⊖=60°) and the structure has been refined by full-matrix least-squares methods to R=0.061. The monomeric structure consists of distorted octahedral ReOL2 units. One oxygen atom of the N3O2 pentadentate ligand is located trans to the rheniumoxo oxygen bond, while the remaining four coordinating atoms lie on the equatorial plane of the octahedron assuming that the oxo-oxygen occupies an apex. The arrangement of the two iminophenolate groups is explained as a function of the length of the aliphatic chain joining the two imine groups.

Monooxorhenium(V) complexes with the tridentate Schiff baseN-(2-hydroxyphenyl)salicylideneimine

SummaryThe reactions of the tridentate Schiff base ligandN-(2-hydroxyphenyl) salicylideneimine (HOPhsalH) with oxotetrachlororhenate (IV) have been investigated. The complexes (Bu4N)[ReOCl3(HOPhsal)], (Bu4N)[ReOCl2(OPhsal)],cis- [ReOCl(MeOH)(OPhsal)],trans-[ReOCl(MeOH)(OPhsal)] (1), trans-[ReOCl(OH2)(OPhsal)] · Et2O (2), trans-[ReOCl(OH2)(OPhsal)] · Me2CO,cis-[ReOCl(PPh3)(OPhsal)],cis-[ReOCl(PMe2Ph)(OPhsal)](3) have been synthesized and characterized. The crystal structures of(1), (2) and(3) have been solved from three-dimensional x-ray data by Patterson and Fourier methods and refined by least-squares methods to R 0.10 for(1), 0.042 for(2) and 0.059 for(3). In all the three complexes, the ligands surrounding the rhenium atom are at the apices of a distorted octahedron, with the equatorial ONO donor atoms of the tridentate Schiff base bent away from the Ooxo and toward the loosely bound MeOH in(1), H2O in(2) and Cl in(t3). The fourth equatorial substituent is Cl (1 and2) and PMe2Ph(3) and the rhenium atoms lie 0.30–0.37 Å above the best plane through the four equatorial atoms, in the direction of the Ooxo. All interatomic distances and angles are normal.

Some palladium(II) and platinum(II) lead bonded complexes

Abstract Complexes of the type M(PPh 3 ) 2 (PbPh 3 ) 2 [M = Pd, (Ia) and Pt, (Ib)] have been prepared by oxidative addition of hexaphenyldilead to M(PPh 3 ) 4 . The compound Pt(PPh 3 ) 2 (PbPh 3 ) 2 , (Ib), slowly decomposes in dichloromethane to give cis -Pt(PPh 3 ) 2 (PbPh 3 )Ph, (II). which can also be obtained by treating (Ib) with the stoichiometric amount of LiPh. Reaction of Pt(PPh 3 ) 4 with hexamethyldidead gives the complex Pt(PPh 3 ) 2 (PbMe 3 )Me directly. The MPb bonds are easily cleaved by bromine, iodine and hydrogen bromide. The X-ray structure of (II) has been determined using three-dimensional counter data and refined by the least-square method ( R = 0.07). The crystals are monoclinic a = 22.501, b = 10.502, c = 24.120 A, β = 113.43°, space group P 2 1 / c with Z = 4. The complex exhibits a cis configuration, with the coordination around the platinum atom essentially square-planar: the PtPb and PtC(phenyl)bond lengths are 2.698(1) and 2.055(3)A, respectively.

Pharmacokinetics and tumor concentration of intraarterial and intravenous cisplatin in patients with head and neck squamous cancer.

SummaryTumor-tissue platinum levels and major pharmacokinetic parameters were determined in 11 patients with head and neck squamous cancer (HNSC) who were given cisplatin (50 mg/m2 daily x 2 days) and 5-fluorouracil (5-FU; 1000 mg/m2, continuous infusion x 5 days) either i.a. or i.v. The plasma peak platinum concentrations (cmax) and the areas under the curve for total platinum concentration versus time (AUC) during i.a. infusions were lower than the i.v.cmax (mean, 1.92±0.28 and 4.08±2.80 mg/l, for i.a. and i.v. infusions, respectively) and AUC values (mean, 22.55±4.96 and 40.66±10.71 mg h−1 l−1 for i.a. and i.v. treatment, respectively), suggesting a first-passage extraction of the drug by the tumor mass during i.a. infusion. However, no statistically significant difference was found in platinum tumor concentrations after i.a. administration versus i.v. infusion. The lack of a difference in tumor platinum concentrations between the i.a. and the i.v. administration routes might be explained either by a relatively high blood supply to the tumor area, enabling efflux of the surplus free platinum from the tissue, or by the delay between drug infusion and biopsy. After three cycles of i.a. treatment good tumor remission was obtained with minimal local toxicity. Larger clinical studies testing the advantages of the i.a. administration route over i.v. infusion appear to be necessary.

X-ray crystallographic characterization of 10,11-dihydro-5H-dibenz[b, f ]azepine-5-carboxamide

The structure of the title compound was determined by the direct methods and refined by fullmatrix least-squares to anR of 0.041 for 1467 diffractometer-measured reflections. The dihedral angle between the aromatic-ring mean planes is 128° and the central seven-membered azepine ring adopts a boat conformation, as usual for compounds of this type. X-ray powder diffraction of the compound indicates that the crystal selected appears to be representative of the sample as a whole.

Binuclear complexes of 1,4-diaza-3-methylbutadien-2-Yl-palladium(II) derivatives with palladium(II) and platinum(II) chlorides

The organometallic 1,4-diazabutadienes, RN=C(R′)C(Me)=NR [R = p-C6H4OMe, R′ = trans-PdCl(PPh3)2 (DAB); PdCl(LL), LL = 1,2-bis(diphenylphosphino)-ethane (DABI), LL = cis-1,2-bis(diphenylphosphino)ethylene (DABII); Pd(dmtc)-(PPh3), dmtc = dimethyldithiocarbamate (DABIII)] react with ethylene or nitrile derivatives of palladium(II) and platinum(II), [PdCl2(CH2 = CH2)]2, K[PtCl3-(CH2=CH2)], [PdCl2(NCMe)2], [PtCl2(NCPh)2] usually to give binuclear complexes of the type [MCl2{RN = C(R′)C(Me)=NR}] (M = Pd, Pt), in which the 1,4-diazabutadiene group acts as a chelating bidentate ligand. The stability of these compounds in hot 1,2-dichloroethane or acetonitrile markedly depends on the nature of the ancillary ligands on the palladium atom of the group R′. When a chelating diphosphine is present, as in the case of DABI and DABII, the corresponding binuclear complexes are recovered unchanged even after long refluxing times. In the case of DAB and DABIII adducts, a transfer of PPh3 and dmtc ligands from the Pd atom of R′ to the metal atom M of the coordinated MCl2 unit occurs with the formation of trans-MCl2(PPh3)2] and of the new bimetallic complexes, [M(dmtc) {RN=C(R″)C(Me)=NR}] (R″ = cis-PdCl2(PPh3) (DABIV)), respectively. The rates of ligand transfer for the PdCl2 adducts are much higher than for the PtCl2 analogues.

Synthesis and X-ray crystal structure of tetraethylammonium bis[1,2-di(carbomethoxy)ethane-1,2-dithiolato]oxotechnetate(V)

SummaryThe (NEt4)+[TcO{SCH(CO2Me)CH(CO2Me)}2]− compound has been prepared from technetium(V) gluconate and characterized by single crystal x-ray structural analysis (R factor=0.065).The compound crystallizes in the monoclinic space groupP21/c witha=12.722(3),b=13.820(4) andc=18.213(5) Å, β=107.13(4)° andZ=4. In the complex the technetium atom is close to the center of the base of a square pyramid in which the oxo oxygen is at the apex and the four sulfur atoms form the basal plane. The Tc-S distances average 2.316 Å. The Tc=O distance is 1.672(6) Å. Considerations about the osteotropic behaviour of DMSA labelled with99Tc are deduced from the reported results.

Preparation and characterization of a new rhenium(V) complex containing the 3-diphenylphosphinopropionylglycyl--(S-benzyl)-cysteinyl methyl ester ligand☆

Abstract A new phosphine derivatized peptide tetradentate ligand containing the PN2S donor atom set, 3- diphenylphosphinepropionylglycyl- l -(S- benzyl ) cysteinyl methyl ester, was synthesized in good yields by coupling a phosphine group to protected Gly- l -Cys dipeptide. Complexation of the new ligand with rhenium proceeded in satisfactory yields by substitution reaction on ReVOCl3(PPh3)2 in a 1.2:1 molar ratio. The resulting rhenium complex was characterized by IR, FAB-MS, 1H and 31P NMR spectroscopy and was found to be neutral and diamagnetic. These studies revealed, that rhenium (V) in a trans-ReOCl2+ cor coordinates with the PN2S2− donor atom set formed by one neutral phosphine, one neutral thioether and two deprotonated amide groups of the ligand forming a neutral complex. High performance liquid chromatography tests verified the purity and high stability of the complex in solution for long periods of time. In alkaline organic media the complex transforms to an equally stable, more hydrophilic analogue, in which the methyl ester group of cysteine is hydrolyzed to the free carboxylate.

Solid-state structure and solution conformation of the nootropic agent N[2-(N,N-Diisopropylamino)ethyl]-2-oxo-1-pyrrolidinacetamide sulphate. X-ray and homonuclear two-dimensional 1H NMR studies☆

Abstract The crystal and molecular structure of the nootropic agent N-[2-(N,N-diisopropyl-amino)ethyl]-2-oxo-1-pyrrolidinacetamide sulphate was determined by X-ray analysis. The conformational properties in the solution state were deduced from the 1H-NMR spectrum run in 2H2O at 500 MHz. Spectral assignments were made with the aid of the COSY 45 shift correlation experiment. Crystals were triclinic with unit cell dimensions a = 13.410(10), b = 11.382(8), c = 6.697(4) » , α = 83.80(3), β = 88.61(3)and γ = 72.25(6)° ; space group P 1 . The structure was determined from 1047 three-dimensional counter data and refined to a value of 7.5% for the conventional discrepancy factor R. One molecule of the solvent acetonitrile is incorporated per two of the (C14H28N3O2)+-(HSO4)−. The five-membered heterocyclic ring is in an envelope (Cs) conformation and the “flap” atom deviates by 0.31 » from the plane of the other four. This plane forms a dihedral angle of 71.4° with the amide group, with the CO fragment directed toward the ring. All bond angles and distances are in good agreement with expected standard values. A strong OH⋯O intermolecular bond (2.61 » ) links the cation of the hydrogen-sulphate anion, while the loosely held MeCN molecule is trapped in the polar pockets. The molecular conformation in the solid was compared with results from 1H NMR spectral analysis which showed that in solution wide torsional oscillations can occur about the bonds of the chain bonded to the N(1) atom.