Theoretical models of eumelanin protomolecules and their optical properties

Abstract

The molecular structure of melanin, one of the most ubiquitous natural pigments in living organisms, is not known and its multifaceted biological role is still debated. We examine structural models for eumelanin protomolecules, based on tetramers consisting of four monomer units (hydroquinone, indolequinone, and its two tautomers), in arrangements that contain an interior porphyrin ring. These models reproduce convincingly many aspects of eumelanin's experimentally observed behavior. In particular, we present a plausible synthetic pathway of the tetramers and their further complexation through interlayer stacking, or through formation of helical superstructures, into eumelanin macromolecules. The unsaturated nature of C-C bonds in indolequinone units and the finite size of protomolecules introduce covalent bond formation between stacked layers. We employ time-dependent density functional theory to calculate the optical absorption spectrum of each molecule along the eumelanin synthesis pathway, which gradually develops into the characteristic broad-band adsorption of melanin pigment due to electron delocalization. These optical spectra may serve as signatures for identifying intermediate structures.

FIGURE 1

Monomer components of DHI-eumelanin and a tetramer composed of them: HQ-MQ-IQ-MQ or HMIM (green, C, red, O, blue, N, and white, H). Atoms in the IQ monomer are numbered in the standard notation.

FIGURE 2

Proposed formation pathway of the IMIM tetramer, as a representative example.

FIGURE 3

Evolution of optical absorbance spectrum along the proposed formation pathway of the IMIM tetramer. These spectra are not renormalized to each other.

FIGURE 4

(a) Dipole moment directions for transitions at 480 nm and 350 nm in the IMIM tetramer. (b) The wavefunctions corresponding to states between which the transitions take place. (c) Total density of states (DOS) of IMIM; the Fermi level is set to zero and the 480 nm and 350 nm transitions between states are indicated by horizontal arrows.

FIGURE 5

Stacking structures of two tetramers: (a) top and (b) side views of the planar stacking of the HMHM-HMHM structure; (c) top and (d) side views of the helical stacking of an IMIM-IMIM structure.

FIGURE 6

Optical absorbance spectrum of two stacked IMIM tetramers in the planar and helical arrangements. The spectrum of constituent IMIM tetramer (magnified by a factor of 2) is also shown for comparison.

FIGURE 7

The effect of Fe binding on the optical absorption of the HMHM tetramer: (a) molecular structure; (b) optical spectra.

FIGURE 8

Incorporation of DHICA component in the tetramer model of eumelanin, in the DHI/DHICA 3:1 ratio (left panel) and 1:1 ratio (middle and right panels). The middle and right panels differ only by the presence of two sugar rings in the latter structure. The optical absorbance for individual molecules is also shown under each structure.