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.