Peter Conrad Healy

Structural and Solution Chemistry of gold(I) and Silver(I) complexes of bidentate pyridyl phosphines: selective antitumour agents

Abstract The 1:2 adducts of Ag(I) and Au(I) with 1,2-bis(di- n -pyridylphosphino)ethane (d n pype) for n =2, 3 and 4 have been synthesised and solution properties characterised by multinuclear NMR spectroscopy. The complexes are hydrophilic analogs of the lipophilic Au(I) antitumour complex [Au(dppe) 2 ] + and the degree of hydrophilicity depends critically on the position of the N atom in the pyridyl ring. The complexes of d3pype and d4pype are simple monomeric [M(d3pype) 2 ] + and [M(d4pype) 2 ] + species which have a much higher water solubility than the 2-pyridyl complexes which crystallise in the solid state as dimeric [{M(d2pype) 2 } 2 ] 2+ . In solution these 1:2 M:d2pype species exist as equilibrium mixtures of monomeric, dimeric and trimeric (Ag) or tetrameric (Au) clusters. The Au(I) and Ag(I)pyridyl phosphine complexes have been evaluated for antitumour activity against a panel of cultured human ovarian carcinoma cell lines. The results show both potent and selective activity for the compounds with IC 50 values ranging from 0.18 to 1500 μM. There is a correlation between the degree of antitumour selectivity and the octanol/water partition coefficients with the greatest selectivity (500-fold range) found for the most hydrophilic complex [Au(d4pype) 2 ]Cl. Clinical development of the parent compound [Au(dppe) 2 ] + was halted by liver toxicity and the hydrophilic pyridylphosphine analogs are significantly less toxic than [Au(dppe) 2 ] + when exposed to isolated rat hepatocytes. Convenient synthetic routes to the bidentate pyridyl phosphines d2pype, d3pype and d4pype are also described.

Lewis-base Adducts of Group 1B Metal(I) Compounds. Part 16. Synthesis, structure and solid-state phosphorus-31 nuclear magnetic resonance spectra of some novel [Cu4X4L4] (X = halogen, L = N, P base) 'cubane' clusters

Recrystallization of [Cu4l4(PPh3)4] from toluene has yielded a new polymorph of that compound, (1), which has been shown by single-crystal X-ray diffraction analysis to have a tetrametallic ‘cubane’ structure rather than the expected ‘step’ structure. Crystals are monoclinic, space group P21/n, with a= 19.47(1), b= 26.94(1), c= 13.528(5)A, β= 98.98(4)°, Z= 4 tetramers; R was 0.06 for No= 3 681. Cu–I distances range from 2.653(3) to 2.732(3)A, with Cu ⋯ Cu 2.874(5)–3.164(4) and I ⋯ I 4.234(2)–4.496(3)A. All adducts of stoicheiometry [M4X4(PPh3)4](M = Cu or Ag; X = Cl, Br, or I) have now been synthesized and structurally characterized in a cubane configuration. Recrystallization of copper(I) chloride and bromide from triethylamine also yields tetrameric cubane 1 : 1 adducts [X = Cl (2) or Br (3)], as does the reaction of copper(I) chloride with the very bulky ligand 2-[bis(trimethylsilyl)methyl]pyridine, to give [Cu4Cl4(tmspy)4](4). These three complexes have also been crystallographically characterized, (2) and (4) being the first reported cubane type tetramers for the copper(I) chloride–nitrogen base system. Complexes (2) and (3) are isostructural with their triethylarsine and -phosphine counterparts, being cubic, space group I3m, with a= 12.162(5)A in (2) and 12.368(3)A in (3); Z= 2 tetramers. Cu–Cl,Br distances are 2.441(4) and 2.537(3)A respectively. For (4), the crystals are tetragonal, space group I41/a, with a= 18.620(4), c= 20.079(5)A, Z= 4 tetramers. Although the Cu4Cl4 cubane core of the molecule has crystallographically imposed symmetry, the geometry is very unsymmetrical as a consequence of the ligand bulk, with Cu–Cl 2.225(2)–2.636(2), Cu ⋯ Cu 2.960(2)–3.194(2), and Cl ⋯ Cl 3.838(3)–3.866(3)A. Residuals R for (2), (3), (4) were 0.040, 0.038, and 0.040 respectively for No= 136, 136, and 1 008 ‘observed’ reflections. The solid-state 31P n.m.r. spectra of the triphenylphosphine cubane clusters show significant differences to those with a ‘step’ geometry; these differences are related to the crystallographic environment of the phosphorus nuclei.

Lewis base adducts of Group 11 metal compounds. Part 24. Co-ordination of triphenylphosphine with silver nitrate. A solid-state cross-polarization magic angle spinning 31P nuclear magnetic resonance, crystal structure, and infrared spectroscopic study of Ag(PPh3)nNO3(n= 1–4)

Solid-state cross-polarization magic angle spinning 31P n.m.r. spectroscopy, single-crystal X-ray structure determination, and i.r. spectroscopy have been used to investigate the properties of the adducts of triphenylphosphine with silver(I) nitrate: Ag(PPh3)NO3, (1); Ag(PPh3)2NO3, (2); Ag(PPh3)3NO3, (3); and Ag(PPh3)4NO3, (4). The value of 1J(Ag–P) decreases with increasing co-ordination number: (1), 780; (2), 470; (3), 310; and (4),190 Hz, paralleling solution results. Single-crystal X-ray structure determinations of compounds (2)–(4) have been performed: (2), triclinic, space group P, a= 11.821(3), b= 11.990(3), c= 13.660(3)A, α= 102.05(2), β= 112.80(2), and γ= 105.30(2)°, yielding R= 0.036 for 4 090 ‘observed’ reflections; Ag–P 2.443(1) and 2.440(1)A, P–Ag–P 138.21(5)°(3), monoclinic, space group P21/n, a= 18.984(5), b= 13.710(3), c= 17.900(4)A, and β= 94.94(2)°, yielding R= 0.053 for 5126 reflections; Ag–P 2.630(2), 2.525(1), and 2.545(2)A, P–Ag–P 118.37(5),112.07(4), and 116.44(5)°; (4), trigonal, space group R, a= 19.07(2), and α= 43.77(5)°, yielding R= 0.060 for 1 903 observed reflections; Ag–P 2.643(3) and 2.671(4)A, P–Ag–P 109.49(12) and 109.45(10)°. Structures (2) and (3)[and (1)] are isomorphous with the analogous triphenylarsine compounds. In all cases the nitrate group is only weakly co-ordinated [and is ionic in (4)]: Ag–O 2.464(4) and 2.649(4) in (2), 2.684(6) and 2.775(6)A in (3). These weak interactions are reflected in the small splitting observed for the asymmetric N–O stretching vibrational mode compared to the analogous copper(I) compounds.

Isolation and crystal structure of an arsenic-containing sugar sulphate from the kidney of the giant clam, Tridacna maxima. X-Ray crystal structure of (2S)-3-[5-deoxy-5-(dimethylarsinoyl)-β-D-ribofuranosyloxy]-2-hydroxypropyl hydrogen sulphate

(2S)-3-[5-Deoxy-5-(dimethylarsinoyl)-β-D-ribofuranosyloxy]-2-hydroxypropyl hydrogen sulphate, (1a) and 3-[5-deoxy-5-(dimethylarsinoyl)-β-D-ribofuranosyloxy]propylene glycol, (1b), have been isolated from the kidney of the giant clam, Tridacna maxima, collected from Shark Bay, Western Australia. The structure of compound (1a) was determined by X-ray diffraction. The source of the arsenicals (1a) and (1b) is likely to be symbiotic, unicellular, green algae living in the clam tissues. As arsenic-containing sugars [including compound (1b)] have previously been isolated from Ecklonia radiata(a macroalga), it is possible that the production of such compounds is a general response of algae to oceanic arsenate.

Lewis-base adducts of group 11 metal (I) compounds. XXVI: Solid-state cross-polarization magic-angle-spinning 31P n.m.r. and structural studies on 1:1 adducts of triphenylphosphine with gold (I) salts

Linear, two-coordinate compounds of molecular formula (PPh3) AuX have been characterized by solid-state and solution 31P n.m.r. spectroscopy, and single-crystal X-ray diffraction techniques. The solid state n.m.r. spectra reveal single, broad resonance lines for X = NO3 (chemical shift 19 ppm , ref. 85% H3PO4), CH3C02 (24 ppm), SCN (36ppm), CN (37 ppm ) and CH3 (47 ppm ) and doublets for X = Cl (27, 33 ppm ), Br (28, 36 ppm ) and I (34, 38 ppm ), the latter three spectra being recorded at 121.47 MHz and 161.96 MHz. Solution spectra show relatively sharp single resonances for each compound with 6 values generally slightly higher than in the solid state. Crystal data are reported for X = NO3, space gro )p P21/c, a 8 895(9), b 10.117(8), c 19.57(2) A; β 97.43(8)o, Au-P,O = 2.199(5), 2.02(1) A. Crystals of compounds with X = Br, I and SCN are isomorphous with the AuCl compound, belonging to space group 212121. For X = Br, a 12.479(5), b 13.45(1), c 10.0!2(8) A; Au-P, Br = 2.252(6), 2.407(2) A. For X = I, a 12.529(8), b 13.870(5), c 10.188(4) A; Au-P, I = 2.254(5), 2.556(2) A. For X = SCN, a 12.257(5), b 13.776(8), c 10.754(6) A; Au-P, S = 2.252(7), 2.304(7) A.

5-Nitrosalicylic Acid and its Proton-Transfer Compounds with Aliphatic Lewis Bases

The crystal structures of the proton-transfer compounds of 5-nitrosalicylic acid (5-nsa) with morpholine (morph), hexamethylenetetramine (hmt), and ethylenediamine (en) have been determined and their solid-state packing structures described. The compounds are [(morph)+(5-nsa)–] 1, [(hmt)+(5-nsa)–·H2O] 2, and [(en)2+2(5-nsa)–·H2O] 3. In all compounds, protonation of the hetero-nitrogen of the Lewis base occurs. With 1, the 5-nsa anions and the morpholine cations lie, respectively, in or across crystallographic mirror planes and are linked within the planes by hydrogen-bonding interactions through the aminium group and the carboxylic and phenolic oxygens of the anionic 5-nsa species giving a two-dimensional sheet polymer. Compound 2 is an unusual structure with the planar 5-nsa anions lying within pseudo mirror planes and cyclically linked by duplex water bridges through a single carboxylate oxygen into centrosymmetric dimers. The hmt cation molecules are disordered across the pseudo mirror and are strongly linked by N+–H···O hydrogen bonds only to the water molecules with peripheral weak hmt C–H···O hydrogen bonds extending the dimer within and between the dimer planes. Compound 3 is a network polymer comprised of the 5-nsa anions, the en dianions, and the water molecule in an extensive hydrogen-bonded structure.

Electrochemical and spectroscopic studies on RuCl2(PPh3)2(N)2 and RuCl2(PPh3)2(N–N) complexes (N=pyridine derivatives and N–N=phenanthroline or bipyridine derivatives). X-ray structure of RuCl2(PPh3)2(phen)

Abstract A series of RuCl2(PPh3)2(N)2 and RuCl2(PPh3)2(N–N) complexes were synthesized from RuCl2(PPh3)3, (N)2=pyridine (py), 4-(N,N-dimethylamino)pyridine (4-dmNpy), 4-tert-butylpyridine (4-tBu-py), 4-methylpyridine (4-Mepy), 4-vinylpyridine (4-Vpy), 4-phenylpyridine (4-Phpy), isonicotinamide (4-CONH2py), 4-cyanopyridine (4-CNpy) N–N=1,10-phenanthroline (phen), 2,2′-bipyridine (bipy), 2,2′-bipyridine-4,4′-dimethoxy (MeO-bipy), 2,2′-bipyridine-4,4′-dimethyl (Me-bipy), 2,2′-bipyridine-4,4′-dithiomethyl (MeS-bipy), 2,2′-bipyridine-4,4′-dichloro (Cl-bipy) and 2,2′-bipyridine-4,4′-dinitro (NO2-bipy). The complexes were characterized by elemental analysis, cyclic voltammetry and UV–Vis, NMR and IR spectroscopies. The structure of the RuCl2(PPh3)2(phen) was established by single crystal X-ray crystallography.

Structure-Making with 3,5-Dinitrosalicylic Acid. II. The Proton-Transfer Compounds of 3,5-Dinitrosalicylic Acid with the Monocyclic Heteroaromatic Amines

The crystal structures of the proton-transfer compounds of 3,5-dinitrosalicylic acid (dnsa) with a series of common monocyclic heteroaromatic amines (pyridine, 4-cyanopyridine, pyridine-4-carboxylic acid, 2,6-diaminopyridine, and 2-aminopyrimidine) have been determined and the hydrogen-bonding associations in each analyzed. The compounds are the adduct [(C5H6N)+(dnsa)–· (dnsa)] (1), the 1 : 1 salts [(C6H5N2)+(dnsa)–] (2), [(C6H6NO2)+(dnsa)–] (3), [(C5H8N3)+(dnsa)–] (4), and the 2 : 2 ethanol hemi-solvate [2(C4H6N3)+·2(dnsa)–· 0.5(EtOH)] (5). With all compounds, protonation of the hetero-nitrogen atom occurs with subsequent hydrogen bonding to the oxygen atoms of the functional groups of the dnsa anions, resulting in the formation of relatively simple linear or chain polymer associations. Compound (1) represents a rare example of other than a 1 : 1 association, and the first example of a 2 : 1 (dnsa/amine) type, with the unusual presence of an additional adduct molecule of dnsa in the structure.

Structure-making with 3,5-dinitrosalicylic acid. I. The proton-transfer compounds of 3,5-dinitrosalicylic acid with a series of aliphatic amines

The crystal structures of the proton-transfer compounds of 3,5-dinitrosalicylic acid (dnsa) with ammonia (two polymorphs) and a series of common aliphatic amines (methylamine, triethylamine, hexamethylenetetramine and ethylenediamine) have been determined and the hydrogen-bonding associations in each analysed. The compounds are [(NH4)+(dnsa)-] (1A, 1B), [(CH3NH3)+(dnsa)-] (2), [{(C2H5)3NH}+(dnsa)-] (3), [(C6H12 N4H)+(dnsa)-] (4) and [{(CH2 NH3) 2}2+(dnsa)2-·H2O] (5). It is of interest that with hydrate (5) the phenolic proton of dnsa is also lost on reaction, giving a rare dianionic species. In all compounds, protonation of the amino group of the Lewis base occurs, with subsequent hydrogen bonding via this and other hydrogens variously to the carboxylic, nitro and phenolic oxygens of dnsa, and in the case of (5), the lattice water. The result is the formation of simple linear associations with the tertiary amines, or network polymers with the less-substituted examples. Short intramolecular hydrogen bonds between the phenolic group and the carboxylate group are found in all compounds except (5), with the proton localized on the carboxylate oxygen rather than on the phenolic oxygen, but in the case of (3), delocalized within the hydrogen bond.

Crystal structures and spectroscopic studies of the mononuclear complex [AgBr(PPh3)2] and binuclear [Ag2X2(PPh3)4]·2CHCl3(X = Cl or Br)

The structure of the silver(I) complexes [AgBr(PPh3)2] and [Ag2X2(PPh3)4]·2CHCl3(X = Cl or Br) have been determined by single-crystal X-ray diffraction. The complex [AgBr(PPh3)2] crystallizes in the monoclinic space group C2/c and contains discrete monomeric [AgBr(PPh3)2] units with essentially trigonal-planar AgBrP2 co-ordination, and a crystallographic two-fold axis of symmetry coincident with the Ag–Br bond. The geometric parameters for the silver atom environment are: Ag–Br 2.568(1), Ag–P 2.458(2)A, P–M–P 124.14(5), P–M–Br 117.93(3)°. The complexes [Ag2X2(PPh3)4]·2CHCl3(X = Cl or Br) are isomorphous, monoclinic, space group C2/c, and contain [Ag2X2(PPh3)4] dimers. Each of the two silver atoms in the structure is four-co-ordinated by forming bonds with the P atoms of the two phosphine ligands and the two doubly bridging halide atoms. The Ag and X atoms lie in a plane, and each of the molecules in the unit cell has a C2 axis which passes through the two X atoms. A chloroform molecule is hydrogen bonded to each X atom. The far-IR spectra of these complexes show bands which are assigned to ν(AgX) modes, and the spectra of these and the unsolvated dimer [Ag2Cl2(PPh3)4] are analysed to yield information about the Ag–X bonding. The Raman spectrum of [AgBr(PPh3)2] shows a band which is assigned to a ν(AgP) mode, an assignement which is confirmed by the observation of similar bands in the Raman spectra of the isostructural gold(I) complexes [AuX(PPh3)2](X = Cl, Br or I). The solid-state cross-polarization magic-angle spinning (CP MAS)31P NMR spectra of the silver complexes show multiplets die to 1J(AgP) coupling. The spectra of the dimers show separate chemical shifts for the crystallographically inequivalent phosphorus atoms, and 2J(PP) coupling between these atoms. The splitting patterns are interpreted in terms of the silver co-ordination environment.