Pyrrolic pigments
Creators: name: Brückner, Christian.
Publisher: name: University of British Columbia
Year: 2009

description: 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]