Ronald R. Fenton

Powder diffraction studies of synthetic calcium and lead apatites

The crystal structures of M10(PO4)6X2, where M = Ca or Pb and X = OH¯, F¯, Cl¯ or Br¯, have been determined by Rietveld refinement of powder synchrotron X-ray and neutron diffraction data. All the compounds are hexagonal with space group P 63/m. For the calcium compounds, the lattice parameters are a = 9.4302(5), 9.3475(3), 9.5902(6), 9.6482(6) and c = 6.8911(2), 6.8646(1), 6.7666(2), 6.7788(2) A, for X = OH¯, F¯, Cl¯, Br¯, respectively. For the lead compounds, the corresponding lattice parameters are a = 9.8612(4), 9.7547(5), 9.9767(4), 10.0618(3) and c = 7.4242(2), 7.2832(2), 7.3255(1), 7.3592(1) A. In these compounds there are two cation sites, a channel of M(I) atoms and a triangle of M(II) atoms. The anion interacts most strongly with the M(II) atoms with the interaction dictating the position of the anion relative to the M(II) triangle. In Ca10(PO4)6X2, the F¯ ion sits within the triangle planes, while the larger OH¯ and Cl¯ anions are disordered above and below the M(II) triangles. The even larger Br¯ is midway between two triangles at (0, 0, ). Despite the larger size of the isostructural lead compounds, no anions are found in the triangles. The F¯, Cl¯ and Br¯ ions are at (0, 0, ) and the OH¯ ion is disordered at (0, 0, z). This difference in behaviour is possibly related to the lead 6s electrons. In this paper, the experimental results are presented and possible reasons for the observed differences are discussed.

Chiral platinum(II) metallointercalators with potent in vitro cytotoxic activity

Four platinum(II) metallointercalating complexes of 1,10‐phenanthroline (phen) with the chiral ancillary ligands trans‐R,R‐ and trans‐S,S‐1,2‐diaminocyclohexane (R,R‐ and S,S‐dach, respectively), and N,N′‐dimethyl‐R,R‐ and N,N′‐dimethyl‐S,S‐1,2‐diaminocyclohexane (Me2‐R,R‐dach and Me2‐S,S‐dach, respectively) have been synthesised and characterised. The crystal structure of [Pt(Me2‐S,S‐dach)(phen)](ClO4)2⋅1.5 H2O (C20H26Cl2N4O9.5Pt) has been determined; orthorhombic, space group P212121(No. 19), a=23.194(8), b=25.131(9), c=8.522(3) Å. In vitro cytotoxic assays (IC50) in the human bladder cancer cell line 5637 and in the murine leukemia L1210 cell line revealed that [Pt(S,S‐dach)(phen)](ClO4)2 (0.091 and 0.13 μM, respectively) and [Pt(R,R‐dach)(phen)](ClO4)2 (0.54 and 1.50 μM, respectively) were more cytotoxic than cisplatin (0.31 and 0.50 μM, respectively) and considerably more cytotoxic than their methylated counterparts, [Pt(Me2‐R,R‐dach)(phen)](ClO4)2 and [Pt(Me2‐S,S‐dach)(phen)](ClO4)2 (both>23 μM). Chiral discrimination for [Pt(S,S‐dach)(phen)](ClO4)2 over its R,R‐enantiomer was observed in all 13 cancer cell lines investigated. Moreover, [Pt(S,S‐dach)(phen)](ClO4)2 was more active than cisplatin in all cell lines tested and shows only partial cross‐resistance to cisplatin in two cisplatin resistant cell lines.

Copper(I) Templated Synthesis of a 2,2´-Bipyridine Derived 2-Catenane: Synthetic, Modelling, and X-ray Studies

Following molecular modelling employing molecular mechanics and semi-empirical (PM3) calculations as an aid to ligand design, a new copper(i)-containing [2]-catenane has been prepared by the reaction of 6,6′-bis[(4″-formylphenoxy)methyl]-2,2′-bipyridyl with 1,6-hexanediamine in the presence of a copper(i) template, followed by in situ sodium borohydride reduction of the tetra-imine species generated. The corresponding [2]-catenane was obtained as a deep orange crystalline solid. The X-ray structure of this product along with that of the corresponding bis-dialdehyde precursor copper(i) complex have been determined. In the latter case, the structure is pre-organized for catenane formation. The new catenane appears to be the first example of a tetrahedral metal template product incorporating a bis-bipyridyl derivative core. Isolation of the metal-free [2]-catenane has also been achieved following treatment of the copper(i) catenane complex in dimethylsulfoxide with tetrabutylammonium cyanide.

In vivo studies of a platinum(II) metallointercalator

An in vivo study for determining the toxicity and efficacy of [Pt(S,S-dach)(phen)Cl(2).1.5H(2)O.0.5HCl (PHENSS) in female Specific Pathogen Free (SPF) Swiss nude mice bearing PC3 tumour xenografts revealed PHENSS to be non-toxic and effective in decreasing tumour growth.

Hydrogen bonding in cis-bis(l-alaninato)copper(II): a single crystal neutron diffraction study

Abstract The structure of cis-bis( l -alaninato)copper(II) {cis-[Cu( l -ala)2]} was determined using single crystal neutron diffraction techniques at both low (7 K) and ambient temperature. At both temperatures the cell is orthorhombic, space group P212121. The unit cell parameters obtained show essentially an isotropic contraction upon cooling. At both temperatures the coordination sphere around the copper atom is best described as square pyramidal, where the fifth position is occupied by a weakly bonded carbonyl oxygen from an adjacent alanine unit. The alanine ligands coordinate to the divalent copper atom in an approximately square planar cis-arrangement. The significant difference between the two structure determinations is the contraction of the apical carbonyl oxygen–copper bond distance from 2.372(4) to 2.326(2) A upon cooling.

Chiral metal complexes 44. Enantiomeric discrimination in ternary cobalt(III) complexes of N,N′-dimethyl-N,N′-di(2-picolyl)-1S,2S-diaminocyclohexane and α-amino acids; including the crystal structure of the S-prolinato complex

Abstract When the C2-symmetrical complex Λ-α[Co(S,S-picchxcMe2Cl2]+ (S,S-picchxnMe2 is N,N′-dimethyl-N,N′-di(2-picolyl)-1S,2S-diaminocyclohexane) is reacted with the α-amino acids proline (proH), alanine (alaH) or 2-amino-2-methylpropandioic acid (AMMAH2), the two chloride ions are replaced by the O,N-bidentates with retention of configuration at the metal centre. The steric environment generated by the metal complex is shown to enantiospecifically discriminate in favour of S-proline from a racemic mixture due to the steric requirements of this amino acid. With the less bulky alanine and AMMAH2 ligands there is no enantiomeric preference observed upon their coordination. When the mixed diastereoisomeric Λ-α-[Co(S,S-piccchxnMe2) (AMMAH)]2+ precursors are decarboxylated under warm acidic conditions, neither hand of alanine is found to predominate in the product. The crystal structure of the Λ-α-[Co(S,S-picchxnMe2) (S-pro)] (ClO4)2· H2O salt of the sole S-prolinate product was determined by X-ray diffraction methods. Crystal data: C25H28N5O11Cl2Co is orthorhombic, space group P2 1 2 1 2 1 , with a = 11.082(3), b = 13.838(4), c = 19.387(5) A and Z = 4 . The structure was refined by least-squares methods to R = 0.033 for 2672 diffractometer data. The Co atom is six-coordinate with the N4-tetradentate and the O,N-bidentate amino acidate comprising the octahedral coordination sphere. The average CoN(pyridine) and Coz.sbnd;N(tert-amine) distance are 1.96 and 2.00 A, respectively.

Polymorphism and Phase Transitions in Bis(glycinato)copper(II). A Powder Diffraction Study

Powder diffraction methods have been used to establish the structures of four known polymorphs of bis(glycinato)copper(II). The two cis-modifications are orthorhombic, and the two trans-complexes are monoclinic. Refinements of the structures, including the location of the hydrogen/deuterium atoms have been achieved utilizing Rietveld analysis of powder data. The cis-monohydrate complex crystallizes in the space group P212121 with lattice parameters a 10.8053(3), b 5.2101(1), and c 13.4983(4) A. Upon dehydration, contraction along the a- and c-axes and elongation of the b-axis is observed. The anhydrous cis-complex also crystallizes in the space group P212121 with lattice parameters a 10.0673(7), b 5.3152(4), and c 13.212(1) A. The trans-hydrated complex crystallizes in the space group I2/a with lattice parameters a 14.8218(3), b 5.2321(1), and c 9.6408(2) A, and β 87.243(1)°. Dehydration of the complex affords the anhydrous modification which crystallizes in the space group P21/c with lattice parameters a 7.0831(6), b 5.1459(4), and c 9.4431(9) A, and β 107.506(4)°. In all four modifications a network of hydrogen bonds stabilizes the complex. This study illustrates the current capabilities of powder diffraction techniques.

Studies on the Nature and Strength of Pt . . .H(-N) Interactions. The Crystal Structures of Chloro[N-(2-aminoethyl)-N-(2-ammonioethyl)ethane-1,2-diamine]platinum(II) Chloride and Dichloro[4,7-diaza-1-azoniacyclononane]platinum(II) Tetrachlor

Two complexes, namely, chloro[N-(2-aminoethyl)-N-(2-ammonioethyl)ethane-1,2-diamine]platinum(II) chloride {[PtCl(tren+H)]Cl2} and dichloro[4,7-diaza-1-azoniacyclononane]platinum(II) tetrachloroplatinate(II)–water (1/2) {[PtCl2(tacn+H)]2[PtCl4]·2H2O}, have been prepared and structurally characterized by single-crystal X-ray diffractometry as part of a study of the nature and strength of Pt···H(–N) interactions. Crystals of [PtCl(tren+H)]Cl2 are monoclinic, space group P21/c, a 8.293(2), b 14.396(6), c 11.305(3) A, β 107.34(2)o, Z 4, and the structure has been refined to a residual of 0.042 based on 1631 reflections. Crystals of [PtCl2(tacn+H)]2[PtCl4]·2H2O are monoclinic, space group P21/a, a 12.834(4), b 8.206(4), c 13.116(8) A, β 93.01(4)˚, Z 2, and the structure has been refined to a residual of 0.035 based on 1974 reflections. In [PtCl(tren+H)]2+, the protonated amine forms hydrogen bonds with chloride anions and no close contacts with the metal ion. In [PtCl2(tacn+H)]+, a short intramolecular contact is observed between the metal and the protonated amine and the results of molecular mechanics modelling are consistent with there being a Pt···H hydrogen bond. Molecular mechanics modelling of [PtCl(tren+H)]2+ and [PtCl2(dien+H)]+ shows that the protonated amines could readily form close contacts with the metal. It is concluded that there is evidence for the formation of Pt···H(–N) hydrogen bonds but these bonds are very weak, being similar or lower in energy than Cl···H(–NPt) hydrogen bonds.

Synthesis, characterisation and in vitro cytotoxicity studies of a series of chiral platinum(II) complexes based on the 2-aminomethylpyrrolidine ligand: X-ray crystal structure of [PtCl2(R-dimepyrr)] (R-dimepyrr = N-dimethyl-2(R)-aminomethylpyrrolidine)

A series of platinum(II) complexes were synthesised based on the enantiomerically pure amino acid proline. Novel synthetic pathways were developed, adapted from standard peptide chemistry, to produce the 2-aminomethylpyrrolidine (pyrr) ligand and its derivatives with differing arrangements of methyl substituents at the exocyclic amine sites. The crystal structure of [PtCl(2)(R-dimepyrr)] (R-dimepyrr=N,N-dimethyl-2(R)-aminomethylpyrrolidine) is reported and the five-membered ligand ring has been shown to be in an envelope conformation. Cytotoxicity studies were carried out on the ovarian cancer A2780 tumour cell line and its cisplatin-resistant variant, A2780cisR. Remarkably good activity was seen for several of the drugs when compared to cisplatin despite the addition of substantial steric bulk to the amine groups, and there was a lack of cross-resistance with cisplatin seen for some compounds.

The Synthesis and in Vitro Cytotoxicity of Two trans-Platinum Complexes of Heterocyclic Amines

The syntheses and crystal structures of the platinum(II) complexes trans-[PtCl2(DMSO)(C4H9NO)] and trans-[PtCl2(DMSO)(dmdze)] are described and the mechanisms leading to their formation are discussed. The complex trans-[PtCl2(DMSO)(C4H9NO)] crystallizes in the triclinic space group P1, a 8.1432(8), b 8.5224(8), c 9.0801(9) A, α 111.780(1), β 91.074(2), γ 98.349(2)°, Z 2, and its structure was refined to an R value of 0.019 on 2470 F. The cytotoxicity of this complex was determined and was found to be lower than that of cisplatin. The complex trans-[PtCl2(DMSO)(dmdze)] crystallizes in the monoclinic space group C2/c, a 23.498(5), b 8.048(2), c 17.859(6) A, β 120.88(2), Z 8, and its structure was refined to an R value of 0.034 on 2712 F.