On the aggregation of bilirubinoids in solution as evidenced by VCD and ECD spectroscopy and DFT calculations

• Published in: Chirality (New York, N.Y.) Vol. 30; no. 1; pp. 19 - 28
• Main Authors: Ghidinelli, Simone, Longhi, Giovanna, Mazzeo, Giuseppe, Abbate, Sergio, Boiadjiev, Stefan E., Lightner, David A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2018
• Subjects: Agglomeration; aggregation; Aliphatic compounds; Amides; Bilirubin; Chains; Chloroform; Circular dichroism; Density functional theory; density functional theory (DFT); Dichroism; Dimers; hydrogen bond; Mathematical analysis; Optical activity; Propionic acid; Spectra; Spectroscopy; Spectrum analysis; vibrational circular dichroism (VCD); bilirubin; vibrational circular dichroism (VCD); dimers; density functional theory (DFT); aggregation; hydrogen bond
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.22776

Vibrational and electronic circular dichroism (VCD and ECD) spectra of 3 optically active bilirubin analogs with propionic acid groups replaced by (1) 1‐(S)‐methylpropyl groups, (2) 3‐acetoxy‐1‐(S)‐methylpropyl groups, and (3) 1‐(S)‐2‐(R)‐dimethyl‐2‐(methoxycarbonyl)ethyl groups have been recorded at different concentrations in chloroform. The aliphatic chains attached to C‐8 and C‐12 of the 3 chosen mesobilirubins were modified so as to possess no OH group. The variation of the VCD spectra with concentration is consistent with the formation of dimers at high concentration. Density functional theory and time‐dependent density functional theory calculations on monomeric and dimeric forms support such a conclusion. Comparing with previous VCD (ECD) and IR (UV) studies of other mesobilirubin molecules, it is concluded that here, the key feature for aggregation is the missing OH groups on the propionic acid chains. The latter, in synergy with the polar groups of lactam moieties, appear to be involved in intramolecular phenomena and thus favor monomeric forms. Investigation of ECD and UV spectra of the same compounds in mixed DMSO/chloroform solutions provide further clues to the proposed picture.