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Paclitaxel, an anti-tumour drug, shows good results against breast and ovarian cancer. However, its therapeutic response is associated with toxic side-effects caused by the agent used to dissolve it. Recently paclitaxel was linked to the linear polysaccharide hyaluronic acid (HA), showing good solubility, stabilization, localization and a reduction of cytotoxic side-effects. To study potential therapeutic applications, HA-paclitaxel bioconjugate (ONCOFID-P) was labelled with 99mTc by the addition of 99mTc-pertechnetate, SnCl2 and sodium gluconate. The reaction mixture was incubated for 90 min at 65°C and purified by size exclusion chromatography. The obtained 99mTc-ONCOFID-P had 100% radiochemical purity and was stable in a phosphate buffer dilution 1:100 for 6 h at 37°C. 99mTc-ONCOFID-P bioavailability studies were carried out in healthy mice using four different administration pathways. The analysis showed that after intravenous administration more than 80% of the injected radiopharmaceutical was found in liver and spleen. Intraperitoneal, intravesical and oral administrations showed that all the 99mTc-ONCOFID-P remained at the administration site. These results demonstrate that ONCOFID-P administered intravenously could be used for liver metastasis therapy due to its high physiological and receptor-specific liver uptake, while intravesical, intraperitoneal and oral administration of ONCOFID-P could be used for local treatment of superficial cancers. Copyright © 2006 John Wiley & Sons, Ltd.

A new (SS)(P) coordination set based on the concurrent use of a dithiocarbamate and a functionalised phosphane is reported. The (SS)(P) fashion is achieved by applying the [2+1] mixed-ligand concept and makes it possible to obtain stable rhenium tricarbonyl complexes without employing tripodal bifunctional chelating agents (BFCAs). The coordination chemistry of the simple sodium N,N-dimethyldithiocarbamate and new functionalised phosphanes L1–L3 [L1 = Ph2PCH2CH2C(O)OCH3, L2 = Ph2PCH2CH2C(O)NHCH2C(O)OCH3, L3 = Ph2PCH2CH2C(O)NHCH2CH2C(O)OCH3] was studied by reaction with the rhenium complex [NEt4]2[fac-Re(CO3)Br3]. The rhenium tricarbonyl core was found to be stabilised by the SS chelation of dithiocarbamate and by the P coordination of the phosphane. Two synthetic pathways leading to the complexes [fac-Re(CO)3(L)(MDTC)] (L = L1, L2, L3; MDTC = N,N-dimethyldithiocarbamate) are described. The structural characterisation of the isolated complexes by spectroscopic methods is reported, including X-ray crystallographic analysis for rhenium complexes with ligands L1 and L3. The homologous Tc-99m compounds with the same (SS)(P) coordination set were prepared at tracer level with the L2 and L3 ligands, and characterised by HPLC methods. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

PN2S coordinate around ReO3+ and TcO3+ cores producing TcO(PN2S) complexes with the ligand acting as tetradentate in the equatorial plane in respect to MO. Two isomers of PN2S-CO2Me have been evidentiated assuming sin-anti positions of the methyl ester group in respect to MO. Labelling experiments with 99mTcO4− and Sn(II)-gluconate, carried out in mild conditions, showed a single compound in high yields referred to the species 99mTcO(PN2S).

The synthesis of Re(I) and 99Tc(I) tricarbonyls complexes has been performed with a new phosphine containing tridentate chelator. Characterization of the complexes showed different coordinative patterns (POO, PNS and PO). All the obtained products were stable to substitution, confirming the phosphine containing peptides as ligands suitable to stabilize the M(CO)3+ moiety.

The complexes [TcL(L′)L″][L″= PEt2Ph, PMe2Ph, or PPh3; L =N-(2-oxidophenyl)salicylideneiminate (L1) or N-(2-sulphidophenyl)salicylideneiminate (L2); L′= quinolin-8-olate (quin) or salicylideneiminate (L3)] were synthesized starting from [TcO(L)(L′)] and characterized by means of physicochemical measurements and for [TcL1(quin)(PEt2Ph)] by means of X-ray analysis. The co-ordination around technetium is approximately octahedral with the phosphine ligand trans to the imino nitrogen of the ligand quin and the tridentate ligand L1 on a plane orthogonal to the line P–Tc–N. The complex crystallizes in the triclinic space group P with a= 14.196(6), b= 11.363(5), c= 9.742(4)A, α= 68.04(3), β= 101.09(3), γ= 106.68(3)°, and Z= 2. The structure has been refined to R= 0.070 for 1 743 independent reflections.

The reactions of ReOX3(PPh3)2 (X = CI or Br) withN-methylsalicylideneimine (Me-saIH),N-phenylsalicylideneimine (Ph-saIH),N,N′-ethylenebis(salicyli(leneimine) [(SaIH)2en] and 8-hvdroxyquinoline (Oxinell) are here reported. They give rise to the ReOX2(Me-sal)PPh2. ReOX-(Me-sal)2, ReOX2(Ph-sal)PPh3, ReOX(Ph-sal),, Re2O2X4-(Sal2en)(PPh3)2, ReOX2(Oxine)PPh, and ReOX(Oxine)2 complexes.

The reactions of the [TcO4]– anion with PPh3 in various concentrations of HCl are reported. [TcCl4(PPh3)2], [TcCl5(PPh3)]–, and [TcCl6]2– were obtained and the anionic complexes were isolated with cations such as [PPh3H]+, [AsPh4]+, or [Ph3PC(Me)2CH2COMe]+. The crystal structure of the title complex was determined at –100 °C from 1 761 independent reflections and refined to R= 0.065. Crystals are monoclinic, space group P21/n, a= 21.909(4), b= 18.963(4), c= 9.896(3)A, β= 103.05(5)°, and Z= 4. The structure consists of well separated units of octahedral [TcCl5(PPh3)]– anions, and tetrahedral phosphonium cations, in which the phenyl groups are in a ′ propeller ′ configuration around P. Selected bond distances and angles are Tc–Cl (mean) 2.34(1), Tc–P 2.57(1)A, Cl–Tc–Cl (mean) 90.7(4), Cl–Tc–P 88.7(4)°.

The reactions of quinquedentate Schiff-base ligands derived from salicylaldehyde and diethylenetriamine (H3L1) or 3,3′-diamino-N-methyldipropylamine (H2L2) with [MO(eg)2]–(M = Tc or Re; H2eg = ethylene glycol) have been investigated. The complexes [MOL1] and [MOL2]+ were produced and characterized by the usual physicochemical measurements. In particular the crystal structure of [TcOL1] was determined by single-crystal X-ray diffraction methods. Crystals are monoclinic, space group P21/c, with a= 9.459(8), b= 9.437(7), c= 21.768(12)A, β= 99.08(5)°, and Z= 4. X-Ray diffraction provided 2 097 observed reflections (up to 2θ= 50°) and the structure has been refined by full-matrix least-squares methods to R= 0.053. The compound consists of discrete TcOL1 molecules with one methanol methanol molecule of crystallization also present in the crystal lattice. One of the oxygen atoms of the quinquedentate ligand is located trans to the technetium–oxo bond, while the remaining four donor atoms occupy the equatorial sites around the Tc atom which resides in a highly distorted octahedral co-ordination environment. The distance between the deprotonated N atom and Tc [1.894(8)A] is significantly shorter than the average for Tc–N single bond lengths.

The crystal and molecular structure of the title compound has been determined from single-crystal X-ray diffractometer data by Fourier methods and refined by anisotropic block-diagonal least-squares to R 0.054 for 4 065 independent observed reflections. Crystals are monoclinic, space group P21/n, with cell parameters a= 10.935(9), b= 39.191(11), c= 13.738(7)A, β= 107.33(7)°, and Z= 8. The two crystallographically independent molecules are stereochemically equivalent (there is only a small difference in the orientation of a benzene ring) and the metal atom has a somewhat distorted octahedral co-ordination, with two pairs of like ligands mutually trans. Technetium–ligand bond distances are: Tc–Cl (trans to P) 2.46(1), Tc–Cl (trans to Cl) both 2.33(1), Tc–P (trans to Cl) 2.42(1) and Tc–P (trans to P) both 2.47(1)A. The noticeble trans-influence of the phosphine ligands on Tc–Cl bonds is discussed.

Some isomers of the ReOX2LPPh3 complexes [X = Cl or Br and L =N-methylsalicylideneiminate,N-phenylsalicylideneiminate, halfN,N∼'-ethylenebis(salicylideneiminate) or 8-hydroxyquinolinate] have been synthesized and characterized. Two different mechanisms for reaction of thetrans-ReOX3(PPh3)2 complexes (X = Cl or Br) with the Schiff bases are supported by qualitative studies on such parameters as the Schiff base ligand form, concentration of free triphenylphosphine ligand, reaction solvent and temperature.

The title complex trans-[Tc(pd)2(PPh3)Cl], prepared by reaction of pentane-2,4-dione(pd) with trans-[Tc(PPh3)2Cl4], crystallises in the centrosymmetric space group P with a= 13.152(8), b= 15.042(10), c= 15.532(13)A, α= 112.26(11), β= 91.01(7), γ= 104.70(9)°, and Z= 4. Intensity measurements have been made with Mo-Kα radiation for the 6 601 independent reflections having 2θ⩽ 44° utilising the θ—2θ scan technique on a diffractometer. The structure has been solved by using the heavy-atom technique and has been refined using full-matrix least-squares procedures to a final R value of 0.063 using 4 950 independent reflections having I > 3σ(I). There are two crystallographically independent molecules which differ chiefly in the folding angles of the pd ligands about the O ⋯ O ‘bite’ axis. The octahedral co-ordination polyhedron is tetragonally elongated and approximates idealised D4h symmetry. The four ‘short’ Tc–O bonds have an average length of 2.01(1)A, while the two ‘long’trans Tc–Cl and Tc–P have lengths of 2.42(1) and 2.46(1)A, respectively. The bonding scheme and trans conformation are discussed in terms of the angular-overlap molecular-orbital model.