Synthetic bacteriochlorins with integral spiro-piperidine motifs

Abstract

A new molecular design incorporates a spiro-piperidine unit in each pyrroline ring of synthetic bacteriochlorins, thereby (1) replacing the previous geminal dimethyl group with a functionally equivalent motif to suppress adventitious dehydrogenation, (2) enabling tailoring of the bacteriochlorin by nitrogen derivatization, and (3) leaving the β-pyrrolic positions available for introduction of auxochromes to tune the spectral properties. Conversion of an N-protected 4-piperidone to the N-protected α,β-unsaturated ketone, Michael reaction with 4-(ethoxycarbonyl)-3-ethyl-2-(2-nitroethyl)pyrrole, and subsequent reductive cyclization provided the spiro-piperidine-1-methyldihydrodipyrrin. Treatment with SeO₂ followed by trimethyl orthoformate under acid catalysis converted the 1-methyl group to a 1-(1,1-dimethoxymethyl) motif. Self-condensation of the resulting spiro-piperidine-dihydrodipyrrin-acetal afforded the 5-methoxy- or 5-unsubstituted bacteriochlorin, each bearing two spiro-piperidine units. The spiro-piperidine units were derivatized at the nitrogens by methylation, sulfonylation, acylation, or quaternization; the latter with methyl iodide afforded two dicationic, hydrophilic bacteriochlorins. Altogether, eight spiro-piperidine-bacteriochlorins were prepared. Spectroscopic characterization was carried out in DMF (and in water for the quaternized, 5-methoxybacteriochlorin). Compared to the 5-unsubstituted analogue, the quaternized, 5-methoxybacteriochlorin has in DMF a shorter wavelength of the intense near-infrared absorption band (733 vs. 752 nm) and fluorescence band (739 vs. 760 nm), modestly greater fluorescence yield (0.15 vs. 0.08) and modestly longer lifetime of the lowest singlet excited state (4.7 vs. 3.3 ns). In general, the spiro-piperidinyl moiety does not significantly alter the rate constants or yields of the decay pathways (fluorescence, intersystem crossing, internal conversion) of the lowest singlet excited state of the bacteriochlorin. Taken together, the results describe a new molecular design for tailoring the polarity of near-infrared absorbers.