Synthesis of compact water-soluble bioconjugatable porphyrins for life sciences applications

Abstract

Porphyrins substituted in a trans-AB pattern bearing a single bioconjugatable group (A) and a single water-solubilizing group (B) with limited molecular weight were synthesized for potential use in aqueous solution. The synthetic approach employed the established reaction of a dipyrromethane and a 1,9-bis(N,N-dimethylaminomethyl)dipyrromethane bearing A and B substituents, respectively, which afforded in low yield the corresponding trans-AB-porphyrin for direct use or subsequent tailoring. Altogether, 30 porphyrins were prepared. The synthetic intermediates entailed the following (given as number of new/known): PEG alkylating agent (1/0), aldehydes (3/6), dipyrromethanes (7/4), and Eschenmoser dipyrromethanes (5/2); totaling 46 new compounds. The candidate bioconjugatable linkers included carboxaldehyde, ethylphenol, phenylisothiocyanate, ethylisothiocyanate, NHS ester of benzoic acid, and NHS ester of phenylpropanoic acid. The water-solubilization motifs included polar groups appended to the two ortho (2,6-) positions of a meso-aryl group. Water solubility was assessed by spectral-band integrity in absorption spectroscopy with a 1000-fold reciprocal change of concentration (0.1-100 μM) and cuvette pathlength (100-0.1 mm). Selected porphyrins were examined for efficacy in bioconjugation. Among all, the most suitable porphyrins were those equipped with (A) a benzoic acid or phenylpropanoic acid group and (B) a meso-aryl group bearing (OCH2CH2)7-CO2H groups at the 2,6-positions. The studies taken together have pruned candidate designs for bioconjugations in dilute aqueous media.