published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

The complexes L(,2)Pt(SR)(,2), where L = PPh(,3), PMePh(,2), PMe(,2)Ph, were prepared in high purity and yield by treating the dichlorides with thiols and triethylamine under nitrogen atmosphere. Their geometry is cis for R = ('n)Pr, ('i)Pr, CH(,2)Ph and trans for R = 4-C(,6)H(,4)Me. Reactions of cis-L(,2)PtCl(,2) and H(,2)S/K(,2)CO(,3) or NaSH in the presence of dichloromethane afforded the complexes L(,2)Pt(S(,2)CH(,2)), containing the novel bidentate methanedithiolato ligand. The thiolato-bridged dimers {LPt(SR')(,2)}(,2), where R' = CH(,2)Ph, 4-C(,6)H(,4)Me, were isolated by fusion of the appropriate monomers in vacuo. The compound {(PMePh(,2))Pt(SCH(,2)Ph)((mu)-SCH(,2)Ph)}(,2) has the cis-symmetrical structure. Treatment of the complexes cis-L(,2)Pt(SCH(,2)Ph)(,2) with phtNSSNpht, where H-Npht = phthalimide, led to stepwise displacement of the phenylmethanethiolato ligands by phthalimido groups. / The first platinadisulfanes, complexes of the type cis-(PPh(,3))(,2)Pt(Npht)(SSR''), where R'' = ('n)Pr, ('i)Pr, CH(,2)Ph, 4-C(,6)H(,4)Me and Npht, were synthesized in good yield by the oxidative addition of R''SSNpht to (PPh(,3))(,2)Pt(C(,2)H(,4)). Similarly, addition of R''SNpht gave cis-(PPh(,3))(,2)Pt(Npht)(SR'').

The influence on the reactivity of both the length as well as the structural nature of diamine bridges linking dinuclear Pt(II) complexes with homotopic bis(2-pyridylmethyl)amine headgroups has been investigated. For this purpose, three sets of square-planar Pt(II) complexes sharing a common non-labile bis(2-pyridylmethyl)amine chelate were synthesized and characterized by various spectroscopic methods. The substitution of the coordinated aqua ligands by three thiourea nucleophiles of different steric demands was studied in acidic aqueous medium under pseudo first-order conditions. The reactions were studied as a function of concentration, temperature and in some cases under an applied pressure using the standard stopped-flow technique and UV-visible spectrophotometry. Their thermodynamic properties were investigated by studying the acid-base equilibria of the coordinated aqua ligands using a spectrophotometric titration method. DFT Quantum mechanical calculations were also performed to determine their geometry-optimized structures and energies of the frontier molecular orbitals. The first set of Pt(II) complexes comprise dinuclears, all bridged by a flexible α,ω-alkyldiamines. The second set of complexes is Pt(II) amphiphilic mononuclear analogues of the former set, formed intuitively by excising off one of the Pt(II) chelate headgroups. The last set of complexes comprises Pt(II dinuclear complexes which are structurally related to the first set, but are linked by relatively rigid linkers, which are made up of either phenyldiamine or diaminocyclohexane fragments. In two of the complexes, a single methylene spacer (CH2 In general, the substitution reactions of the coordinated aqua ligands of all the Pt(II) complexes by the three sulfur donor nucleophiles (Nu) proceed via a two-step reaction pathway. The first step, whose rate constant is denoted in subsequent text as k) group is incorporated between the rigid moieties of the diamine bridge so as to elongate the average distances separating their Pt(II) atoms as well as to modulate the rigidity of the complexes. For comparison purposes, two monomeric analogues bearing the phenyl and cyclohexyl appended groups, respectively, were studied and reported together with these complexes. 2(1st), involves the substitution of the aqua ligands. The second step, induced by the coordination of the strong labilizing thiourea nucleophiles and whose rate constant is denoted in the text as k2(2nd), is ascribed to the dechelation of the one of the cis-coordinated pyridyl units. Thus, the substitution of the aqua ligands and the subsequent dechelation of the pyridyl units, can be expressed as kobs(1st/2nd) = k2(1st/2nd)[Nu] for all the reactions. Negative entropy of activation, negative volume of activation (in cases where measurements were carried out) and second-order kinetics for the substitution reactions all support an associative mode of activation. The substitution reactivity of all the dinuclear complexes is influenced to a greater extent by the steric influences conferred by the bridge as well as a weak electronic effect. The steric influences are mutual, axially exerted and seemingly unique to the square-planar terdentate chelate headgroups. The steric influences depend strictly on length of the diamine (i.e., the average distances separating the Pt centres of the dinuclears) as well as molecular symmetries and shapes of the complexes. The molecular symmetries and hence the shapes of the complexes depend on the parity of the connecting bonds in the diamine (whether even or not). If the connecting bonds of the bridges are even, C2h structures and hence slip-up molecular geometry are preferred. Their overlap geometries cause mutual and axial steric influences on the Pt(II) square-planar chelates which retard substitutional reactivity when the bridge is short. When odd, bowl-shaped complexes of the C2v point group symmetry are preferred in which the axial steric influences are absent at their Pt(II) chelates. In addition their bowl geometry causes an entrapment of the incoming nucleophiles, causing unusually high reactivity when compared to their even-bridged counterpart. For both molecular symmetries (C2h or C2v), the reactivity of the dinuclear complex depends on the average distances separating the Pt(II) centres of the dinuclears. In the former type of complexes, when the average distances separating their Pt(II) centres are long, the axial steric influences at each Pt(II) chelate due to their C2h The chain length as well as the structural make-up of the linker also determines the amount of electron density donated inductively from the linker to the Pt ions as well as the effective nuclear charge at each Pt(II) centre due to charge addition. These are two opposing overlap geometry is weakened, leading to enhanced reactivity as the chain length is increased. In the latter type of complexes, this weakens the ‘entrapment’ effect of their bowl-shaped geometry, resulting in a steady decrease in reactivity when the chain length of the linker is increased. In addition rigidity and planarity within the backbone of the diamine bridge has been found to distort the bowl cavity causing weakening of the ‘entrapment effect’ resulting in the lower rates than expected. iv factors which also influence the rate of substitution in these complexes to some extent. The inductive effect as well as the presence of a domineering steric influence in the C2h overlap geometry was verified by studying the reactivity of the analogous amphiphilic Pt(II) complexes. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2009.

The influence on the reactivity of both the length as well as the structural nature of diamine bridges linking dinuclear Pt(II) complexes with homotopic bis(2-pyridylmethyl)amine headgroups has been investigated. For this purpose, three sets of square-planar Pt(II) complexes sharing a common non-labile bis(2-pyridylmethyl)amine chelate were synthesized and characterized by various spectroscopic methods. The substitution of the coordinated aqua ligands by three thiourea nucleophiles of different steric demands was studied in acidic aqueous medium under pseudo first-order conditions. The reactions were studied as a function of concentration, temperature and in some cases under an applied pressure using the standard stopped-flow technique and UV-visible spectrophotometry. Their thermodynamic properties were investigated by studying the acid-base equilibria of the coordinated aqua ligands using a spectrophotometric titration method. DFT Quantum mechanical calculations were also performed to determine their geometry-optimized structures and energies of the frontier molecular orbitals. The first set of Pt(II) complexes comprise dinuclears, all bridged by a flexible α,ω-alkyldiamines. The second set of complexes is Pt(II) amphiphilic mononuclear analogues of the former set, formed intuitively by excising off one of the Pt(II) chelate headgroups. The last set of complexes comprises Pt(II dinuclear complexes which are structurally related to the first set, but are linked by relatively rigid linkers, which are made up of either phenyldiamine or diaminocyclohexane fragments. In two of the complexes, a single methylene spacer (CH2) group is incorporated between the rigid moieties of the diamine bridge so as to elongate the average distances separating their Pt(II) atoms as well as to modulate the rigidity of the complexes. For comparison purposes, two monomeric analogues bearing the phenyl and cyclohexyl appended groups, respectively, were studied and reported together with these complexes. In general, the substitution reactions of the coordinated aqua ligands of all the Pt(II) complexes by the three sulfur donor nucleophiles (Nu) proceed via a two-step reaction pathway. The first step, whose rate constant is denoted in subsequent text as k2(1st), involves the substitution of the aqua ligands. The second step, induced by the coordination of the strong labilizing thiourea nucleophiles and whose rate constant is denoted in the text as k2(2nd), is ascribed to the dechelation of the one of the cis-coordinated pyridyl units. Thus, the substitution of the aqua ligands and the subsequent dechelation of the pyridyl units, can be expressed as kobs(1st/2nd) = k2(1st/2nd)[Nu] for all the reactions. Negative entropy of activation, negative volume of activation (in cases where measurements were carried out) and second-order kinetics for the substitution reactions all support an associative mode of activation. The substitution reactivity of all the dinuclear complexes is influenced to a greater extent by the steric influences conferred by the bridge as well as a weak electronic effect. The steric influences are mutual, axially exerted and seemingly unique to the square-planar terdentate chelate headgroups. The steric influences depend strictly on length of the diamine (i.e., the average distances separating the Pt centres of the dinuclears) as well as molecular symmetries and shapes of the complexes. The molecular symmetries and hence the shapes of the complexes depend on the parity of the connecting bonds in the diamine (whether even or not). If the connecting bonds of the bridges are even, C2h structures and hence slip-up molecular geometry are preferred. Their overlap geometries cause mutual and axial steric influences on the Pt(II) square-planar chelates which retard substitutional reactivity when the bridge is short. When odd, bowl-shaped complexes of the C2v point group symmetry are preferred in which the axial steric influences are absent at their Pt(II) chelates. In addition their bowl geometry causes an entrapment of the incoming nucleophiles, causing unusually high reactivity when compared to their even-bridged counterpart. For both molecular symmetries (C2h or C2v), the reactivity of the dinuclear complex depends on the average distances separating the Pt(II) centres of the dinuclears. In the former type of complexes, when the average distances separating their Pt(II) centres are long, the axial steric influences at each Pt(II) chelate due to their C2h overlap geometry is weakened, leading to enhanced reactivity as the chain length is increased. In the latter type of complexes, this weakens the ‘entrapment’ effect of their bowl-shaped geometry, resulting in a steady decrease in reactivity when the chain length of the linker is increased. In addition rigidity and planarity within the backbone of the diamine bridge has been found to distort the bowl cavity causing weakening of the ‘entrapment effect’ resulting in the lower rates than expected. The chain length as well as the structural make-up of the linker also determines the amount of electron density donated inductively from the linker to the Pt ions as well as the effective nuclear charge at each Pt(II) centre due to charge addition. These are two opposing factors which also influence the rate of substitution in these complexes to some extent. The inductive effect as well as the presence of a domineering steric influence in the C2h overlap geometry was verified by studying the reactivity of the analogous amphiphilic Pt(II) complexes. / Thesis (D.Phil.)-University of KwaZulu-Natal, 2009. / National Research Foundation and University of KwaZulu-Natal

Thesis (Ph. D.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 226-235).

Thesis (Ph.D.)--Montana State University--Bozeman, 2004. / Typescript. Chairperson, Graduate Committee: Edwin H. Abbott. Includes bibliographical references (leaves 264-268).

It is generally accepted that platinum antitumour drugs bind, preferentially, to Guanine N7 in DNA. Thus the kinetics of formation and the energetics of dissociation of platinum-nitrogen bonding have been investigated, using simple model bases, namely pyridine. pyrimidine. purine and some derivatives. Six complexes of the type cis-PtCl2L2, where L is a N-heterocycle, have been successfully prepared and characterized. The kinetics of the reaction between K2PtCl4 and the N-heterocyclic bases in aqueous solution have beeD studied. This was best achieved by pre-aquating the PtCl4(2-) and measuring the decrease in concentration of platinum or ligand by AA or UV spectroscopy respectively. It was found that the rate of reaction is second order, the rate being dependent on the concentration of both platinum complex and the ligand. The substitution of ligand takes place by direct replacement, involving an associative S.2 mechanism. It was found that the activation entropy and the activation energy for the reactions of platinum complexes in solution are strongly correlated. The energetics of platinum-nitrogen bond dissociation were followed using thermogravimetric analysis. Quantitative data, which enabled calculation of the activation energy for the decomposition process involving the loss of one molecule of ligand was obtained from isothermal studies. No correlation was found between the solid state studies, involving bond breaking, and the syntheses of the complexes, probably because in solution the reaction is complicated by solvent effects. Theoretical studies, which involved Molecular Orbital calculations on the N-heterocyclic bases themselves, were also carried out in an attempt to correlate the kinetic and energetic parameters with the electronic structure of the ligand. Several correlations were attempted but only one was found. This was the relationship between the solid state decomposition energy and the LUMO energy of the quarternized base.

In this study a method was developed to identify and quantify platinum(II) complexes of the type [PtCl4-n(OH)n]2- and [PtCl4-n(H2O)n]2-n. Separation of the various species was achieved with the aid of a hyphenated reversed phase HPLC-ICP-MS technique coupled with an ion-pairing reagent, HMHDCl2. The adsorption of HMHD2+ onto a C-18 column was investigated by generating a series of breakthrough curves. It was found that the selectivity for high charge density anions originates from its low surface coverage relative to TBA+, which on the other hand could not separate Pt(II) complexes. The peaks in the chromatographic traces were assigned by following the stepwise ligand substitution of [PtCl4]2- in hydroxide medium with UV/Vis spectrophotometry and HPLC-ICP-MS simultaneously. A computer program was written by the author to analyse chromatographic data by deconvoluting the chromatogram into its individual components and calculating the mole fraction of each component. The validity of the consecutive pseudo-first order model was validated by constructing 3D Mauser diagrams with the raw spectrophotometric data (A1 vs A2 vs A3). Additional software was used to simulate the raw spectrophotometric data and processed chromatographic data. The pseudo-first order rate constants obtained in both cases were in agreement with each other. Hence, peaks were assigned to [PtCl4]2-, [PtCl3(OH)]2-, [PtCl2(OH)2]2-, [PtCl3(H2O)]-. The molar extinction coefficient spectra of [PtCl3(OH)]2- and [PtCl2(OH)2]2- were obtained by simulating the spectrophotometric data at wavelengths from 280 to 450 nm. The reaction of [PtCl4]2- with sodium hydroxide was investigated with UV/Vis spectrophotometry at 25 °C. A rate constant consisting of a first and second order term was obtained. The first order term agreed with what has been reported in the literature for aquation of [PtCl4]2- at 25 degrees C. The influence of temperature was established by conducting the experiment at different temperatures. It was found that the reaction proceeds essentially via aquation at elevated temperatures.

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published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy