Supramolecular interactions playing an integral role in the near-infrared Raman "excitonic" enhancement observed in β-hematin (malaria pigment) and other related heme derivatives.

To gain more understanding into the mechanism that enables the dramatic resonant Raman enhancement of totally symmetric modes observed in hemozoin (malaria pigment) and other related heme supramolecular arrays when applying near-infrared excitation wavelengths, the iron(III) porphyrins Fe(TPP)Cl, Fe(TPP)O, Fe(OEP)Cl, and Fe(OEP)O along with β-hematin (synthetic hemozoin or malaria pigment) were analyzed in the solid state using resonance Raman spectroscopy. The critical finding was that from the model compounds investigated, all except Fe(OEP)O exhibited the enhancement of the totally symmetric mode ν(4) when exciting the molecules with 782 and 830 nm laser lines. Through a detailed comparison of X-ray crystallographic structures, it is proposed that intermolecular noncovalent interactions play an integral role in enabling excitonic interactions to occur in these heme supramolecular systems. Comparison of the solid- and solution-phase electronic spectra in the near-IR region indicated more absorbance in the solid state between 800 and 900 nm. The electronic spectrum of Fe(OEP)O shows minimal absorbance in this region compared to that of the other compounds. All heme derivatives investigated have similar structure with a five-coordinate high-spin iron(III) ion. The crystallographic data indicate no significant differences in porphyrin geometry between TPP and OEP derivatives studied. However, Fe(OEP)O contains less supramolecular interactions in comparison to the other species. The supramolecular bonding enhances the probability of through-space interactions between the transition dipoles from electronic transitions of extended π systems. Our results indicate that the intensity of ν(4) is in part strongly affected by C-H···X hydrogen bonding interactions when X is an electron-donating entity. Such information may have important implications in the design and monitoring of antimalarial drugs that specifically interfere with hemozoin formation.