pKa values of aqua ligands of platinum (II) anticancer complexes: [1H, 15N] and 195Pt NMR Studies of cis- and trans- [PtCl2 (NH3) (Cyclohexylamine)]

Syntheses and NMR studies are reported of two 15N-labelled Pt(II) complexes of anticancer interest: cis-PtCl2(15NH3)(c-C6H1115NH2), a metabolite of the orally-active Pt(IV) complex cis,trans,cis-[PtCl2(acetate)2(c-C6H11NH2)(NH3), and trans-[PtCl2(15NH3)(c-C6H1115NH2), a reduction product of the active Pt(IV) complex trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2). For cis-[PtCl2(15NH3)(c-C6H1115NH2), hydrolysis was faster for the chloride ligand trans to cyclohexylamine, and the pKa values determined by [1H, 15N NMR spectroscopy for the two cis monoaqua isomers were the same (6.73). The trans monoaqua complex was a stronger acid with pKa of 5.4 (determined by 195Pt NMR). For the cis diaqua complex, pKa values of 5.68 and 7.68 were determined.

Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones

The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC(50) values of ca. 200 nM.

Synthesis of a 1,4-benzodiazepine containing palladacycle with in vitro anticancer and cathepsin B activity

The reaction of the five-membered C,N-palladacycle [(L)PdCl](2), where LH = 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, with 1,2-ethanebis(diphenylphosphine), dppe, leads to the formation of the bridged palladacycle. [Pd(2)L(2)(mu-dppe)Cl(2)] 3, which was characterised in solution by (1)H and (31)P NMR spectroscopy and in the solid state by X-ray crystallography. Complex 3 was tested in vitro against a number of cell lines. For example, it inhibited K562 leukaemia cells with an IC(50) value of 4.3 microM (1 h exposure) and displayed cathepsin B inhibitory action with an IC(50) value of 3 microM.

Review paper: role of aluminum in glass-ionomer dental cements and its biological effects

The role of aluminum in glass-ionomers and resin-modified glass-ionomers for dentistry is reviewed. Aluminum is included in the glass component of these materials in the form of Al(2)O(3) to confer basicity on the glass and enable the glass to take part in the acid-base setting reactions. Results of studies of these reactions by FTIR and magic-angle spinning (MAS)-NMR spectroscopy are reported and the role of aluminum is discussed in detail. Aluminum has been shown to be present in the glasses in predominantly 4-coordination, as well as 5- and 6-coordination, and during setting a proportion of this is converted to 6-coordinate species within the matrix of the cement. Despite this, mature cements may contain detectable amounts of both 4- and 5-coordinate aluminum. Aluminum has been found to be leached from glass-ionomer cements, with greater amounts being released under acidic conditions. It may be associated with fluoride, with which it is known to complex strongly. Aluminum that enters the body via the gastro-intestinal tract is mainly excreted, and only about 1% ingested aluminum crosses the gut wall. Calculation shows that, if a glass-ionomer filling dissolved completely over 5 years, it would add only an extra 0.5% of the recommended maximum intake of aluminum to an adult patient. This leads to the conclusion that the release of aluminum from either type of glass-ionomer cement in the mouth poses a negligible health hazard.

Excellent correlation between cathepsin B inhibition and cytotoxicity for a series of palladacycles

The reaction of the five- or six-membered C,N or C,S-palladacycles [(L)PdCl](2) with PTA (1,3,5-triaza-7-phosphaadamantane) led to the monomeric complexes [(L)Pd(PTA)Cl] 6a, 6b and 7 where LH= N,N-dimethyl-1-phenylmethanamine, benzyl(methyl)sulfane or 1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one respectively. Dimeric complexes have also been synthesised: [Pd(2)L(2)(mu-dppe)Cl(2)], where LH = 1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (1a), (R)- or (S)-3-isopropyl-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (1b, 1c), [Pd(2)L(2)(mu-dppf)Cl(2)], where L= 1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (4a) or (R)-3-isopropyl-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (4b), respectively, and dppe = 1,2-bis(diphenylphosphino)ethane, dppf = 1,1'-bis(diphenylphosphino)ferrocene. The complexes were characterised in solution, by (1)H and (31)P NMR spectroscopy, and single crystals of complexes 6b and 7 were studied in the solid state by X-ray crystallography. The palladacycles were evaluated for in vitro activity as cytotoxic agents on A2780/S cells and also as cathepsin B inhibitors, an enzyme implicated in a number of cancer related events.