title: Bioconjugatable porphyrins bearing a compact swallowtail motif for water solubility.
abstract: A broad range of applications requires access to water-soluble, bioconjugatable porphyrins. Branched alkyl groups attached at the branching site to the porphyrin meso position are known to impart high organic solubility. Such "swallowtail" motifs bearing a polar group (hydroxy, dihydroxyphosphoryl, dihydroxyphosphoryloxy) at the terminus of each branch have now been incorporated at a meso site in trans-AB-porphyrins. The incorporation of the swallowtail motif relies on rational synthetic methods whereby a 1,9-bis(N-propylimino)dipyrromethane (bearing a bioconjugatable tether at the 5-position) is condensed with a dipyrromethane (bearing a protected 1,5-dihydroxypent-3-yl unit at the 5-position). The two hydroxy groups in the swallowtail motif of each of the resulting zinc porphyrins can be transformed to the corresponding diphosphate or diphosphonate product. A 4-(carboxymethyloxy)phenyl group provides the bioconjugatable tether. The six such porphyrins reported here are highly water-soluble (> or =20 mM at room temperature in water at pH 7) as determined by visual inspection, UV-vis absorption spectroscopy, or 1H NMR spectroscopy. Covalent attachment was carried out in aqueous solution with the unprotected porphyrin diphosphonate and a monoclonal antibody against the T-cell receptor CD3epsilon. The resulting conjugate performed comparably to a commercially available fluorescein isothiocyanate-labeled antibody with Jurkat cells in flow cytometry and fluorescence microscopy assays. Taken together, this work enables preparation of useful quantities of water-soluble, bioconjugatable porphyrins in a compact architecture for applications in the life sciences.
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
authors.forename: K Eszter
authors.initials: KE
authors.lastname: Borbas
authors.forename: Pawel
authors.initials: P
authors.lastname: Mroz
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Lindsey
mesh_terms: D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism*; D019169:Jurkat Cells; D015394:Molecular Structure; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D013057:Spectrum Analysis; D014867:Water / Q000737:chemistry*
chemical_list: D007074:Immunoglobulin G; D011166:Porphyrins; D014867:Water