This thesis work reports developments in the coordination chemistry of ruthenium porphyrin complexes, both in terms of the synthesis and chemistry of new compounds, as well as the study of the solution chemistry of some previously reported complexes. The synthesis, characterization and chemistry of ten new Ru(porp) coordination complexes in the oxidation states Ru[superscript]Ⅲ and Ru[superscript]Ⅳ containing halide (Br, CI) and other axial ligands (pyridine, CH₃CN, NH₃ and SbF₆) are described in this thesis. Some additional ten Ru(porp) complexes have been studied in situ. Measurement of the rate constants for forward and reverse reactions and the corresponding equilibrium constant by 'H NMR and UV/visible spectroscopy for the dissociation of PPh₃ ligand from Ru(OEP)L(PPh₃) (OEP is the octaethylporphyrinato dianion; L = CO, PPh₃) in C₇D₈ to generate the previously reported five-coordinate Ru(OEP)L complexes allowed for an estimation of the Ru-P bond strength (64 ± 9 kJ mol⁻¹) in these complexes. A study of PPh₃ dissociation from Ru(OEP)CO(PPh₃) in C₇D₈ and in CDC1₃ indicates that solvation effects play a major role, with CDC1₃ being more capable than C₇D₈ of solvating the Ru(OEP)CO complex. The presence of trace H₂0 in these systems was a major problem, and the coordination of H₂0 to Ru(OEP)L complexes to generate the in situ Ru(OEP)L(H₂0) complexes (L = CO, PPh₃) is described. The formation of Ru(OEP)L(H₂0) and the observed difference in the solvation of Ru(OEP)CO by C₇H₈ and CHC1₃ indicate that truly Five-coordinate species may not exist in solution. The outer-sphere oxidation of Ru [superscript]Ⅳ(OEP)PPh₃ by 0₂ to give [Ru [superscript]Ⅳ(OEP)OH]₂0 was shown to occur only in the presence of H₂0. Mechanistic studies on the previously reported reaction of HCI with [Ru(OEP)]₂ to generate Ru^(OEP)Cl₂ (C. Sishta, M.Sc.Thesis, University of British Columbia, 1986) show that solvent plays a major role in directing this oxidation reaction. A reaction stoichiometry of 4:1 between HCI and [Ru(OEP)]₂ in C₆D₆ or C₇D₈ showed that HCI itself was the oxidant and not trace Cl₂ in HCI, as thought previously. A range of HX acids having pK[subscript]a, values in the range 38 to less than -10 (HX = H₂, MeOH, H₂0, H₂S, CH₃COOH, C₆H₅COOH, HF, CF₃COOH, HN0₃, HBF₄, HCI. HBr, and HSbF₆) were tested for reactivity with [Ru(OEP)]₂in C₆D₆; the data showed that a strong acid (pK[subscript]a < ca. 0) was necessary to initiate reactivity. The complex Ru[superscript]Ⅳ(OEP)(SbF₆)₂ was generated in situ by reacting HSbF₆ with [Ru(OEP)]₂. In CH₂C1₂, a 1:1 stoichiometric reaction between HCI and [Ru(OEP)]₂ was observed, instantly fanning a mixture of products, tentatively formulated as Rura(OEP)H and [Ru[superscript]Ⅲ(OEP)]₂CHCl₂ based on spectroscopic data. The species proved impossible to separate. These same products were formed slowly by the reaction of [Ru(OEP)]₂ with CH₂C1₂ in the absence of HCI, and kinetic studies suggest that a direct reaction of [Ru(OEP)]₂ with CH₂C1₂ is likely, rather than reaction of [Ru(OEP)]₂ with impurities in CH₂C1₂. The product mixture generated Ru(OEP)Cl₂ upon further reaction with HCI, both in the absence and in the presence of air. The complex Ru[superscript]Ⅳ(OEP)(BF₄)₂ was generated in situ by an analogous reaction of aqueous HBF₄ with the product mixture. The required hydrogen-containing co-product from the reaction of HX (X = Br, CI) with [Ru(OEP)|₂ in C₇D₈ or CH₂C1₂ was not detected, but was shown not to be H₂. Oxidation of Ru(porp)(CH₃CN)₂ and Ru(OEP)py₂ (py = pyridine; porp = OEP, TMP (the dianion of tetramesitylporphyrin)) by gaseous HX (X = Br, CI) in the absence of air yielded Ru[superscript]Ⅳ(porp)X₂ complexes. The new compound Ru(TMP)Br₂ was synthesized by this method using the bis(acetonitrile) precursor, and was characterized by spectroscopy; the chloride analogue Ru(TMP)Cl₂ was generated in situ. The magnetic properties (susceptibility and moment) of Ru(OEP)Br₂ from 6 to 300 K are unlike those reported for ruthenium(IV) non-porphyrin complexes, and reveal a significant contribution from temperature-independent paramagnetism. The reaction of Ru(OEP)X₂ (X = Br, CI) with NH₃ gave the complexes Ru[superscript]Ⅲ(OEP)X(NH₃), which upon acidification under an inert atmosphere yielded the Rum(OEP)X compounds. These Ru111 complexes were characterized by spectroscopic techniques, and the solution chemistry of the five-coordinate species Ru(OEP)X was developed: the Ru[superscript]Ⅲ(OEP)X(CH₃CN) species were also characterized. Solvation of the five-coordinate species Ru(OEP)X (X = Br, CI) was observed in coordinating solvents to form the six-coordinate species Ru(OEP)X(solvent) (solvent = py, CH₃CN and MeOH). Estimates of the equilibrium constants for the association of these ligands to Ru(OEP)X were obtained from UV/visible titration experiments in CH₂C1₂. Similarly, the equilibrium constant for the association of Br to Ru(OEP)Br to generate in situ (n-Bu)₄N⁺[Ru[superscript]Ⅲ(OEP)Br⁺₂]", was measured. Disappointingly, the complexes Ru(OEP)X were shown not to catalyze the oxidation of organic substrates such as cyclohexene. Electrochemical and spectroelectrochemical studies of the complexes Ru(OEP)X₂ and Ru(OEP)X (X = Br, CI) showed that the Ru[superscript]Ⅳ/Ru[superscript]Ⅲ couple occurred at 480-460 mV and 950-870 mV vs. NHE, respectively, and that the probable reductant for the reaction of Ru(OEP)X₂ with NH₃ was NH₃ itself. A facile reduction of Ru(OEP)(SbF₆)₂ gave the complex Ru[superscript]Ⅲ(OEP)SbF₆, by a probable homolysis of the Ru-F bond. The outer-sphere oxidation of Ru(OEP)py₂ by air in the presence of HX acids gave the isolated or in situ characterized complexes [Ruin(OEP)py₂]+ X" (X = CI, Br, F, BF₄). Similar oxidation of Ru(OEP)(CH₃CN)₂ formed [Ru(OEP)(CH₃CN)₂]+ Br-. Electrochenucal studies showed that 0₂ in acidic media was capable of oxidizing the Ru(OEP)(solvent)₂ complexes (solvent = py, CH₃CN) to the Ru[superscript]Ⅲ complexes, presumably generating H0₂ . / Science, Faculty of / Chemistry, Department of / Graduate

Interaction of metalloporphyrins, particularly of the iron subgroup, with gas molecules such as 0₂ and CO, remains of considerable interest in terms of comparison with natural heme protein systems. This thesis describes studies on ruthenium(II) porphyrin complexes, the second row analogues of the heme systems. Toluene solutions of the bis(acetonitrile) complex RuOEP(CH₃CN) ₂, (OEP = the dianion of octaethylporphyrin) with or without excess acetonitrile present, are irreversibly oxidized by 0₂ at 30°C. However, with CO, the complex undergoes a clean reaction to give RuOEP(CO)(CH₃CN) with several isosbestic points observed in the UV/VIS spectrum. The kinetic dependence on the CO pressure and acetonitrile concentration are consistent with a dissociative mechanism: [Chemical Reaction I] The kinetic rate constants, k-₁, k-₂ and k-₁/k₂ and the overall equilibrium constant were determined at 30°C in toluene. The Ru0EP(P(n-Bu) ₃) ₂ complex, in toluene, is completely unreactive toward 0₂ at 30°C over a period of several days; although again a monocarbonyl is formed under a CO atmosphere. In the presence of excess P(n-Bu) ₃, under CO, an equilibrium mixture of RuOEP(P(n-Bu) ₃) ₂ and RuOEP(CO)(P(n-Bu) ₃) is formed. The equilibrium constant K for reaction (II) and the thermodynamic parameters AH (3.7 Kcal/mole) and ΔS (10.3 e.u.) are determined along with the rate constants for the dissociative mechanism (cf. Equation I). The low ΔH value implies comparable bond [Chemical Reaction II] strengths between ruthenium and the two ligands P(n-Bu) ₃ and CO. The k -₁/k₂ values for the acetonitrile and phosphine systems are thought to relate to the structure of the five-coordinate intermediate, RuOEP(L); the data suggest the ruthenium is probably more in the porphyrin plane than out of plane, al least compared to analogous iron systems. The major difference between the acetonitrile and phosphine systems is in the k₂value which varies by 10⁵ , partially due to the difference in ir-acidity of the two axial ligands. Toluene solutions of RuOEP(CH₃CN) ₂ bind N₂ and C₂H₄ very weakly. However, due to the extreme photo- and oxygen-sensitivity of the products, no consistent kinetic data could be obtained. Solutions of RuOEP(py) ₂ in neat pyridine, formed in situ from the bis(acetonitrile) complex in pyridine, are completely unreactive toward CO. Even toluene solutions with small amounts of pyridine react only partially (~15% in three days at 25°C) to give the monocarbonyl. Upon dissolving the RuOEP(CH₃CN) ₂ complex in DMA, DMF and THF, the species formed seem to be RuOEP(CH₃CN)(solvent). These species react with CO at 30°C in a two step reaction, an instantaneous part followed by a much slower one; the reactions appear to involve the rapid formation of one monocarbonyl followed by decomposition to the expected monocarbonyl, RuOEP(CO)(solvent). Decarbonylation of the amide solvent to give an amine ligand may be involved in the fast reaction. Judging by the reaction with CO (non-first-order in ruthenium) there are possibly two species present when RuOEP(CH₃CN) ₂ is dissolved in pyrrole, RuOEP(pyrrole)₂ and RuOEP(CH₃CN)(pyrrole), which react at different rates. / Science, Faculty of / Chemistry, Department of / Graduate

Study of the diseases of porphyrin metabolism has formed a major part of the work of the C.S.I.R.- U.C.T. Renal metabolic Research Group since 1959. The scope of the activities of this Group has been wide; this thesis concerns but one aspect, the excreted porphyrins. This is essentially a laboratory study but it is a study that would have lost much of its significance had it not been closely linked to the clinical studies of other members of the group, in particular Prof. L. Eales. The unit has formed a stimulating environment in which to pursue these investigations and it is a. pleasure to acknowledge the contributions to this thesis of all members of the group.

Bulk heterojunction organic solar cells (BHJ OSCs) have been fascinated in recent years for the future green energy generation due to their most promising results of low-cost fabrication, great flexibility, and lightweight properties. Very recently small molecule donors in the BHJ active layers have shown prominent attention due to the synergistic advantages over the polymer counterparts, which possess easy purification, highly facile synthesis, and negligible batch-batch variations. To construct push-pull molecules for p-type semiconductors, acceptor-donor-acceptor (A-D-A) based backbone exalted so far. In addition, the most impressive small molecule electron-donor units (D) are like benzodithiophene (BDT), oligothiophene, 3-dithienosilole (DTS), and indacenedithiophene (IDT) and so on. Likewise, electron-acceptors (A), such as 3-alkylrhodanine, diketopyrrolopyrrole (DPP), and perylenediimide (PDI) have been utilized. Porphyrin derivatives show excellent photochemical and electrochemical properties. Interestingly, porphyrins can be easily modified by different substituents at the peripheral positions (meso- and β-) and metal insertions at the center of the porphyrin core. In this work, we design, synthesize and characterize visible-near infrared absorbing new porphyrin dimer based small molecules with acceptor-donor-acceptor (A-D-A) configuration for bulk heterojunction organic solar cells, and investigate their structure-property relationships, specifically the effect of conjugation and planarity of the backbone central units on the charge mobility, film morphology, and solar cell performances. Chapter 1 deals with an overview of the past and recent development of BHJ OSCs, particularly the key principles and photovoltaic characteristics. Furthermore, we focus on the detailed classification of porphyrin-based small molecules and their performances in OSCs. In chapter 2, two promising near-IR absorbing porphyrin-based dimeric small molecules were designed and synthesized, in which diketopyrrolopyrrole-ethynylene-bridged porphyrin dimers are capped with electron-deficient 3-ethylrhodanine (A2) via a π-bridge of phenylene ethynylene, with an optimal A2-π-D-A1-D-π-A2 architecture affording porphyrin dimers DPP-2TTP and DPP-2TP. They possess strong absorption in ranges of 400-550 (Soret bands) and 700-900 nm (Q bands). Their intrinsic absorption deficiency between the Soret and Q bands could be perfectly compensated by a wide bandgap small molecule DR3TBDTTF with absorption in 500-700 nm. Impressively, the optimal ternary device based on the blend films of DPP-2TPP, DR3TBDTTF (20 wt.%) and PC71BM, shows a PCE of 11.15%, while the binary devices based on DPP-2TTP/PC71BM and DPP-2TP/PC71BM blend films exhibit PCEs of 9.30% and 8.23%, respectively. The high compatibility of the low bandgap porphyrin dimers with the wide bandgap small molecule provides a new threesome with PC71BM for highly efficient panchromatic ternary organic solar cells. Chapter 3 describes another two new A-π-D-π-A structural porphyrin small molecules denoted as TDPP-2P and TDPPE-2P which are constructed from dimeric porphyrin linked by 2,5-bis(2-butyloctyl)-3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (TDPP), and 2,5-bis(2-butyloctyl)-3,6-bis(5-ethynyl-2-thienyl)-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (TDPPE), respectively, further π-extended symmetrically with electron-deficient 4-[(3-ethyl-4-oxo-2-thioxo-5-thiazolidinylidene)methyl]-phenylethynyl fragments. Compared to the absorption spectra of TDPP-2P, astonishingly TDPPE-2P improves the range of near-infrared over 1000 nm due to the enhanced coplanarity of the central core. Moreover, the intrinsic absorption deficiency (500-700 nm) is perfectly compensated by IT-M small molecule acceptor. Remarkably the blend film TDPPE-2P:IT-M accomplished panchromatic photo-current absorption from 400-900 nm, as a result, the device exhibits a prominent PCE of 5.69%. Whereas, the film TDPP-2P:IT-M shows comparatively low PCE of 4.12%. Finally, we believe that such a combination of TDPPE-2P:IT-M device demonstrates synergetic compatibility of donor/acceptor domain to promote the complementary absorption spectrum and enhances through higher hole mobilities and better crystallinity of the surface and interface for non-fullerene small-molecule organic solar cells. In Chapter 4, we further modified and synthesized a new series of A*-π-D2-D1-D2-π-A* based porphyrin dimer (2P) (D2) small molecules flanked by 4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-2,6-diethynylbenzo[1,2-b:4,5-b']dithiophene (TBDTE) and 4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene (TBDT) as TBDTE-2P and TBDT-2P respectively, in which benzodithiophene (BDT) (D1) based analog was constructed as a central unit because of extended coplanarity conjugation length. Finally, TBDTE and TBDT units end-capped with 3-ethylrhodanine (A*) via a π-bridge of phenyl ethynyl linker and 2-octyldodecan-1-al long alkyl chain was used on vertical meso-porphyrins to improve the material solubility for the solution-processed OSCs. The compound TBDTE-2P accomplishes absorption range from 400-800 nm in the vis-near-infrared region, whereas TBDT-2P compound absorbs 400-700 nm range. The higher absorption range of TBDTE-2P arises from more planar backbone orientation and strong intramolecular charge transfer (ICT) within the donor molecules. Further, we focus on the OPV performances of binary devices TBDTE-2P / TBDT-2P: IDIC under AM 1.5G 1-Sun and 300 lux LED illuminations. The champion device TBDTE-2P: IDIC was accumulated a PCE of 7.46% under 1-Sun whereas a PCE of 12.34% was obtained under indoor light illuminations. The exploit of superior properties, charge generation and collection, hole and electron mobilities, and atomic force microscopy (AFM) were also examined. In Chapter 5, we synergistically designed and synthesized two new porphyrin dimers triply fused at meso-meso, β-β and βꞌ-βꞌ positions, from the corresponding meso-meso singly-linked porphyrin arrays. These fused porphyrin tapes differ by two metal atoms at the porphyrin core, such as zinc and nickel, termed as F-C19ZnP and F-C19NiP, respectively. With the purpose for design new acceptor-donor-acceptor small molecules for OSCs, the two fused porphyrin tapes were investigated in detail on the photophysical and electrochemical properties. Both fused porphyrins exhibit a strong and wide Soret-band absorption from 400-570 nm. Interestingly, the compound F-C19ZnP is recorded a larger red-shift absorption than the compound F-C19NiP consistent with cyclic voltammetry (CV) measurements, because the Zn-porphyrin attains more planar conjugated geometry. Finally, the dissertation was completed with a summary in chapter 6

Bulk heterojunction organic solar cells (BHJ OSCs) have been fascinated in recent years for the future green energy generation due to their most promising results of low-cost fabrication, great flexibility, and lightweight properties. Very recently small molecule donors in the BHJ active layers have shown prominent attention due to the synergistic advantages over the polymer counterparts, which possess easy purification, highly facile synthesis, and negligible batch-batch variations. To construct push-pull molecules for p-type semiconductors, acceptor-donor-acceptor (A-D-A) based backbone exalted so far. In addition, the most impressive small molecule electron-donor units (D) are like benzodithiophene (BDT), oligothiophene, 3-dithienosilole (DTS), and indacenedithiophene (IDT) and so on. Likewise, electron-acceptors (A), such as 3-alkylrhodanine, diketopyrrolopyrrole (DPP), and perylenediimide (PDI) have been utilized. Porphyrin derivatives show excellent photochemical and electrochemical properties. Interestingly, porphyrins can be easily modified by different substituents at the peripheral positions (meso- and β-) and metal insertions at the center of the porphyrin core. In this work, we design, synthesize and characterize visible-near infrared absorbing new porphyrin dimer based small molecules with acceptor-donor-acceptor (A-D-A) configuration for bulk heterojunction organic solar cells, and investigate their structure-property relationships, specifically the effect of conjugation and planarity of the backbone central units on the charge mobility, film morphology, and solar cell performances. Chapter 1 deals with an overview of the past and recent development of BHJ OSCs, particularly the key principles and photovoltaic characteristics. Furthermore, we focus on the detailed classification of porphyrin-based small molecules and their performances in OSCs. In chapter 2, two promising near-IR absorbing porphyrin-based dimeric small molecules were designed and synthesized, in which diketopyrrolopyrrole-ethynylene-bridged porphyrin dimers are capped with electron-deficient 3-ethylrhodanine (A2) via a π-bridge of phenylene ethynylene, with an optimal A2-π-D-A1-D-π-A2 architecture affording porphyrin dimers DPP-2TTP and DPP-2TP. They possess strong absorption in ranges of 400-550 (Soret bands) and 700-900 nm (Q bands). Their intrinsic absorption deficiency between the Soret and Q bands could be perfectly compensated by a wide bandgap small molecule DR3TBDTTF with absorption in 500-700 nm. Impressively, the optimal ternary device based on the blend films of DPP-2TPP, DR3TBDTTF (20 wt.%) and PC71BM, shows a PCE of 11.15%, while the binary devices based on DPP-2TTP/PC71BM and DPP-2TP/PC71BM blend films exhibit PCEs of 9.30% and 8.23%, respectively. The high compatibility of the low bandgap porphyrin dimers with the wide bandgap small molecule provides a new threesome with PC71BM for highly efficient panchromatic ternary organic solar cells. Chapter 3 describes another two new A-π-D-π-A structural porphyrin small molecules denoted as TDPP-2P and TDPPE-2P which are constructed from dimeric porphyrin linked by 2,5-bis(2-butyloctyl)-3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (TDPP), and 2,5-bis(2-butyloctyl)-3,6-bis(5-ethynyl-2-thienyl)-2,5-dihydro-pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (TDPPE), respectively, further π-extended symmetrically with electron-deficient 4-[(3-ethyl-4-oxo-2-thioxo-5-thiazolidinylidene)methyl]-phenylethynyl fragments. Compared to the absorption spectra of TDPP-2P, astonishingly TDPPE-2P improves the range of near-infrared over 1000 nm due to the enhanced coplanarity of the central core. Moreover, the intrinsic absorption deficiency (500-700 nm) is perfectly compensated by IT-M small molecule acceptor. Remarkably the blend film TDPPE-2P:IT-M accomplished panchromatic photo-current absorption from 400-900 nm, as a result, the device exhibits a prominent PCE of 5.69%. Whereas, the film TDPP-2P:IT-M shows comparatively low PCE of 4.12%. Finally, we believe that such a combination of TDPPE-2P:IT-M device demonstrates synergetic compatibility of donor/acceptor domain to promote the complementary absorption spectrum and enhances through higher hole mobilities and better crystallinity of the surface and interface for non-fullerene small-molecule organic solar cells. In Chapter 4, we further modified and synthesized a new series of A*-π-D2-D1-D2-π-A* based porphyrin dimer (2P) (D2) small molecules flanked by 4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-2,6-diethynylbenzo[1,2-b:4,5-b']dithiophene (TBDTE) and 4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene (TBDT) as TBDTE-2P and TBDT-2P respectively, in which benzodithiophene (BDT) (D1) based analog was constructed as a central unit because of extended coplanarity conjugation length. Finally, TBDTE and TBDT units end-capped with 3-ethylrhodanine (A*) via a π-bridge of phenyl ethynyl linker and 2-octyldodecan-1-al long alkyl chain was used on vertical meso-porphyrins to improve the material solubility for the solution-processed OSCs. The compound TBDTE-2P accomplishes absorption range from 400-800 nm in the vis-near-infrared region, whereas TBDT-2P compound absorbs 400-700 nm range. The higher absorption range of TBDTE-2P arises from more planar backbone orientation and strong intramolecular charge transfer (ICT) within the donor molecules. Further, we focus on the OPV performances of binary devices TBDTE-2P / TBDT-2P: IDIC under AM 1.5G 1-Sun and 300 lux LED illuminations. The champion device TBDTE-2P: IDIC was accumulated a PCE of 7.46% under 1-Sun whereas a PCE of 12.34% was obtained under indoor light illuminations. The exploit of superior properties, charge generation and collection, hole and electron mobilities, and atomic force microscopy (AFM) were also examined. In Chapter 5, we synergistically designed and synthesized two new porphyrin dimers triply fused at meso-meso, β-β and βꞌ-βꞌ positions, from the corresponding meso-meso singly-linked porphyrin arrays. These fused porphyrin tapes differ by two metal atoms at the porphyrin core, such as zinc and nickel, termed as F-C19ZnP and F-C19NiP, respectively. With the purpose for design new acceptor-donor-acceptor small molecules for OSCs, the two fused porphyrin tapes were investigated in detail on the photophysical and electrochemical properties. Both fused porphyrins exhibit a strong and wide Soret-band absorption from 400-570 nm. Interestingly, the compound F-C19ZnP is recorded a larger red-shift absorption than the compound F-C19NiP consistent with cyclic voltammetry (CV) measurements, because the Zn-porphyrin attains more planar conjugated geometry. Finally, the dissertation was completed with a summary in chapter 6

No description available.

Yes / The retention of photochemical properties of individual chromophores is a key feature of biological light harvesting complexes. This is achieved despite extensive aggregation of the chromophores, which in synthetic chromophore assemblies often yields a change in spectral characteristics. As an alternative approach towards mimicking biological light harvesting complexes, we report the synthesis of porphyrin assemblies which retained the photochemical properties of the individual chromophore units despite their substantial aggregation. These new materials highlight a new bottom-up approach towards the design and understanding of more complex biomimetic and naturally occurring biological systems. / Seventh Framework Programme (European Commission) (FP7), Engineering and Physical Sciences Research Council (EPSRC), Royal Society (Great Britain)

Texaphyrins represent the vanguard of experimental anticancer drugs and also symbolize a well-known example of expanded porphyrins, a class of oligopyrrolic macrocycles with tumor localization properties and powerful metal chelating properties. Chapter 1 of this thesis describes the unique structural characteristics of this complex synthetic molecule along with the biological relevance and scientific justifications for studying its anticancer properties and powerful MRI contrast ability. This Chapter also serves to underscore the need to improve further and refine the efficacy of texaphyrins as compounds that may be applied in the struggle against cancer. Chapter 2 details the synthesis of bismuth(III) and lead(II)-texaphyrin complexes that could potentially find use as [alpha]-core emitters for radiotherapy. In principle, porphyrins would ostensibly appear to be ideal ligands for use in radiotherapy due to their tumor-localizing ability. However, Bi(III)- and Pb(II)-porphyrin complexes are extremely rare, most reflecting the vastly challenging synthesis of these compounds as well as their general lack of stability. These limitations provided an incentive for us to use texaphyrins as more versatile ligands to prepare and fully characterize stable bismuth(III) and lead(II) complexes. To be of interest in future medical applications, we needed to prepare these complexes quickly as compared to the relevant time scales set by the half-lives of the isotopes targeted for use in radiotherapy. This goal was successfully realized. As mentioned above, texaphyrin is able to form stable complexes with a large variety of metals particularly in the lanthanide series. Gadolinium(III) complexes of texaphyrin have been studied in considerable detail. Chapter 3 details the synthesis and conjugation methods used to develop a texaphyrin conjugated dual mode nanoparticle contrast agent. This project has been done in collaboration with the group of Prof. Jinwoo Cheon (Yonsei University, Seoul, Korea), who demonstrated fascinating results with the texaphyrin functionalized nanoparticles. Not only do these conjugates act as improved magnetic resonance contrast agents displaying enhanced signals in both the T1 and T2 MRI modes, but also serve to sensitize apoptotic hyperthermia. It is this latter, double effector feature, that has been most extensively studied to date. Chapter 4 of this dissertation describes work done in close collaboration with Dr. Natalie Barkey and Dr. David Morse (Moffitt Cancer Center, Tampa, FL) where a gadolinium texaphyrin complex was developed that is able to target the melanocortin 1 receptor (MC1R) when encapsulated in a micellar system. As detailed in this Chapter, these collaborateurs demonstrated that these gadolinium-texaphyrin micelles are able to target MC1R-expressing xenograft tumors in vivo. This work relied on the supply of a new set of texaphyrin derivatives that were prepared and characterized as part of this dissertation work Chapter 5 of this disseration introduces sapphyrins, another class of expanded porphyrins with tumor selectivity. This project is based on the hypothesis that a direct linkage of sapphyrin with an anticancer agent based on ruthenium(II) could improve the efficacy of both compounds. Since sapphyrins exhibit limited ability to form stable complexes with transition metals, an appended 1,10-phenanthroline unit was chosen as an efficient N-donor aromatic ligand for ruthenium(II). Therefore, extensive synthetic efforts were made to form this sapphyrin-1,10-phenanthroline construct in an effort to stabilize a mixed sapphyrin-metallo-phenanthroline complex. Finally, Chapter 6 of this dissertation demonstrates the author's efforts to synthesize a planar rosarin species. Non-aromatic and non-planar rosarins have been known for over two decades. Through structural modification of the compound, namely through linking of both [Beta] positions on the bipyrrole unit, a new planar rosarin species has been synthesized exhibiting Hückel antiaromaticity. / text

Student Number : 0010064D - MSc dissertation - School of Chemistry - Faculty of Science / This dissertation describes the synthesis, physical characterisation and solution chemistry of NAc-CoIIIMP8, a biomimetic model compound of vitamin B12a, synthesised from the haemoctapeptide derived from horse heart cytochrome c. Peptic and tryptic digestion of horse heart cytochrome c removes much of the globular protein encapsulating the iron porphyrin prosthetic group. The resulting haemoctapeptide fragment retains residues 14 to 21 of the parent cytochrome (MP8) via thioether linkages to Cys-14 and Cys-17. Reductive demetalation of MP8 yielded the metal free MP8. This was treated with cobaltous acetate in an aerated aqueous solution to produce CoIIIMP8. CoIIIMP8 was acetylated by treatment with acetic anhydride and yielded N-acetyl-Co(III)- microperoxidase 8 (NAc-CoIIIMP8). It is well established that acetylation reduces aggregation of these haempeptides. The starting materials and products of each step during synthesis were characterised by UV-visible absorption spectroscopy, high performance liquid chromatography (HPLC) and fast atom bombardment-mass spectroscopy (FAB-MS). MP8 free base and Co(III)-MP8 were also analysed using luminescence spectroscopy. The molar extinction coefficients of NAcCoIII-MP8 in aqueous and ionic medium were determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and UV- visible absorption spectroscopy. The extinction coefficient, e, of NAcCoIIIMP8 (? = 420 nm, pH 7.00, 25 ºC) in distilled water and 1.0 M NaClO 4 was 1.80 + 0.01 x 105 M-1 cm-1 and 1.66 + 0.01 x 105 M-1 cm-1, respectively. Beer’s law studies show that NAc-CoIIIMP8 remains monomeric in aqueous solution up to concentrations of at least 35 μM. The spectroscopic changes observed for NAc-CoIIIMP8 during the course of a spectrophotometric titration are very similar to those observed for NAc-FeIIIMP8, with both being consistent with six successive ionisations. By analogy with NAc-FeIIIMP8, we attributed the first (pK1 = 2.0 + 0.3) to the coordination of the c-terminal carboxylate group (Glu-21) of the appended polypeptide. The second acid range transition (pK2 = 2.8 + 0.1) for NAcCoIIIMP8 involved the deprotonation of the cationic His-18 and concomitant replacement of the c-terminal carboxylate by the neutral heterocyclic base. The third and fourth pKa’s are attributed to the ionisation of the haem propanoic acid groups (pK3 = 3.9 + 0.03) and (pK4 = 7.5 + 0.03). Ionisation of the cobalt-bound water molecule above neutal pH was assigned to pK5 = 9.2 + 0.04. Finally, we attributed pK6 (12.1 + 0.03) to the ionisation of the coordinated histidine trans to the OH- to form the histidinate complex (His--CoIII-OH-). A principal aim of this work was to demonstrate that the kinetics and the thermodynamics of the ligand substitution reactions of NAc-CoIIIMP8 can be studied spectrophotometrically; a comprehensive investigation of these reactions will be undertaken by othe rs. Towards this end the formation constants between NAc-CoIIIMP8 and N- methylimidazole and pyridine were determined. We observed the formation of a bis-substituted complex in the reaction of NAc-CoIIIMP8 with the ligands, but only mono-substitution with NAc-FeIIIMP8 and B12a. We attribute this first ligand binding to the replacement of the axial water molecule, and the second replacement of the axial histidine residue. The absence of the second reaction with NAc-FeIIIMP8 and B12a suggest that the CoIII-N(His) bond in NAc-CoIIIMP8 is significantly weaker than the FeIIIN( His) and CoIII-N(dimethylbenzimidazole) bond, respectively. When comparing the formation constants of NAc-FeIIIMP8, NAc-CoIIIMP8 and B12a, we found that the value of log K1 for NAc-CoIIIMP8 for these ligands is significantly higher than that reported for NAc-FeIIIMP8 and B12a. Kinetics studies of NAc-CoIIIMP8 with N-methylimidazole and methylamine were investigated. The data obtained did not follow conventional pseudo-first order kinetics; instead there was some evidence for biphasic kinetics. In the reaction of Nmethylimidazole with NAc-CoIIIMP8, we observed that the rate of reaction is virtually independent of the concentration of the incoming ligand. The results can be explained if the mechanism proceeds through a purely dissociative mechanism, i.e., if the rate of the reaction is controlled by the rate at which, firstly, the water molecule dissociates from the CoIII centre and, secondly, the histidine dissociates from the metal. The second order rate constant, k2, could not be determined since the rate of reaction is independent of Nmethylimidazole concentration. In the reaction of methylamine with NAc-CoIIIMP8, we observed that the rate of reaction is dependent on the concentration and participation of the incoming ligand. We propose that the displacement of water and histidine by methylamine involves an interchange mechanism (Id), where the bond forming and bond breaking occur simultaneously, and thus the rate of reaction becomes dependent on the concentration of the incoming ligand. The results showed that the rate of reaction for methylamine with NAc-CoIIIMP8 was faster than with N-methylimidazole. We attributed these differences in rate constants to the size of the incoming ligands. N-methylimidazole is a secondary amine and is relatively more bulky than methylamine which is a primary amine; therefore it is easier for methylamine to attach to the metal centre compared to N- methylimidazole. For comparison, the rate of reaction of B12a with N-methylimidazole and methylamine was determined. The results show that the rate of the reaction between NAc-CoIIIMP8 and B12a with N-methylimidazole and methylamine are significantly different. Furthermore, we observe only mono -substitution in B12a and bisubstitution in NAc- CoIIIMP8. Overall, the results presented in this work do give a general indication on how thermodynamically stable a CoIII ion is in a porphyrin ring and also to a very limited extent show that a porphyrin does not confer the same kinetic lability on the CoIII ion as the corrin ring.

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