| Summary: | Part 1 presents studies aimed at the synthesis of novel aromatic tetra- and
pentapyrrolic pigments with meso-phenyl substituents and with long wavelengths of
absorption. Such compounds are potential photosensitizers for use in photodynamic therapy
(PDT). Several approaches are described:
1. The osmium tetroxide mediated dihydroxylation of variously substituted mesotetraphenylporphyrins
(TPP) to provide novel stable chlorins such as 129 and bacteriochlorins
such as 141 and 146 is reported. The directing effect of the central metal zinc in the
stereo- and regiochemical outcome of the dihydroxylation of meso-tetraphenylchlorins is
outlined. The resulting 8,6'-dihydroxylated amphiphilic chlorins are characterized by
spectroscopic and analytical techniques. Preliminary in vitro biological results of their
potency as drugs in PDT have been encouraging. One side-product of the osmylation
reaction, the 2-oxa-3-oxochlorin 163, was structurally characterized by X-ray
crystallography. [Model not included]
Some unique physical (observable rotation of the phenyl groups) and chemical
properties of the 6,6'-diolchlorins are reported. For instance, me,«?-tetraphenyl-2,3-vjcdihydroxy-
2,3-chlorinato)nickel(II) can be converted oxidatively into the corresponding 2,3-
secochlorin-2,3-dialdehyde 167. This compound can ring-close to the novel double ketal 175. This severely distorted pigment has been structurally characterized by X-ray
crystallography and is without precedent. [Model not included] 2. A directed synthesis of N-confused porphyrin 104 was developed. The key step in
the synthesis was a 2+2-type condensation of dipyrromethane 197 with the novel a,6-linked
dipyrromethane 190. Although the goal of producing 104 in high yields could not be met,
this study provided valuable insight into the chemistry of dipyrromethanes and provided
through fortuitous circumstance tripyrrane 180. [Model not included] 3. Tripyrrane 180 is the key reagent in the directed high-yield synthesis of meso-phenylsapphyrins
such as 200. As inferred from spectroscopic properties, the protonation
dependent conformation of 200 is described. 4. Studies towards the elucidation of the mechanism of formation of porphycyanines via
the lithium aluminum hydride (LAH) reduction pathway of 2-cyanodipyrromethanes are
presented. To this end, variously substituted 2-cyanopyrroles were prepared and reduced by
LAH. It was found that imine linked dimers such as 204 are directly formed during this
reduction. A mechanistic proposal for this outcome is presented. A unique reaction of 204
with nickel(II) to form the tripyrrolic complex 236 is described. The complex was
structurally characterized by X-ray crystallography and its mode of formation has been
rationalized. [Model not included] Part 2 describes the synthesis of 5-phenyldipyrromethane (20) and the conversion
into the corresponding raeso-phenyldipyrrins (11). Their ability to complex to transition
metals is described and the optical spectra of the resulting dipyrrinato complexes of
nickel(II), copper(II), and zinc(II) are discussed in depth, compared to known
alkyldipyrrinato complexes and correlated to their structure. The special steric properties of
the novel me so -phenyl dipyrrins are highlighted by the structural characterization of two
unusual complexes, namely the square planar diamagnetic nickel(II) complex 27 and
octahedral copper(III) complex 48. [Model not included] Part 3 describes the improved preparation of dipyrromethane 2 by direct
hydrodesulfurization of thione 7 with Raney-nickel/H2- It was also found that
2-pyrrolylthiones chelate in an N,S-bidentate fashion to a variety of transition metals. The
preparation of, for instance, the square planar nickel(II) (29), octahedral copper(III) (33, two
isomers) and tetrahedral mercury(II) (32) chelates of 7 are described and their spectroscopic
properties are correlated to their structures. The steric requirements for the dipyrrolylthione
ligand were determined. These complexes as well as the free base 7 were structurally
characterized by X-ray crystallography. Furthermore, the synthesis of the 2-thioacetylpyrrole
and 2-thiobenzoylpyrrole and their nickel(II) and cobalt(III) complexes is described.
This is the first report of the complexing ability of the 2-pyrrolyl moiety. [Model not included] === Science, Faculty of === Chemistry, Department of === Graduate
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