Conformational Analysis\nof Swallowtail Motifs in Porphyrins

Aqueous solubilization of porphyrins,\noften accomplished\nwith appended\npolar aryl groups, can also be achieved with symmetrically branched\nalkyl (i.e., swallowtail) groups terminated with polar moieties. Here,\ncarboxylic acids are employed as termini (versus prior phosphono-\nor phosphoester termini) in designs of <i>trans</i>-AB-porphyrins\nbearing a single swallowtail group (A) or <i>trans</i>-A<sub>2</sub>-porphyrins bearing two swallowtail groups. Variable-temperature <sup>1</sup>H NMR studies (−60 to 97 °C) revealed that the\n4-heptanedioic acid group at the meso-position of the free base porphyrin\nrotates with rate constant 5 s<sup>–1</sup> (310 K) and Arrhenius\nenergy barrier <i>E</i><sub>a</sub> = 11.5 kcal/mol, whereas\nan isopropyl group undergoes rotation ∼1000-times faster (<i>k</i> = 5770 s<sup>–1</sup>). The interconversion is\nsufficiently fast that conformational diastereomers, as when two such\nswallowtail groups are present in a <i>trans</i>-A<sub>2</sub>-porphyrin, would not be isolable at room temperature (Class I atropisomers).\nDFT calculations (4 porphyrins containing the isopropyl or 4-heptanedioic\nacid groups) showed that the lowest energy conformer contains the\nswallowtail C–H unit in the plane of the porphyrin. The presence\nof one or two 4-heptanedioic acid moieties imparted solubility of\nthe porphyrin in phosphate-buffered saline (PBS). The results suggest\napplications in the life sciences where compact, aqueous-soluble porphyrins\nare desired.