The DOPA scaffold: Tracing catechol chemistry from prebiotic earth to cognitive agency

Abstract

L-3,4-dihydroxyphenylalanine (DOPA) is primarily defined by its role as the precursor to catecholamine neurotransmitters, a view substantiated by its status as the gold-standard treatment for Parkinson's disease. This framing obscures its profound evolutionary significance. This review reframes DOPA as a fundamental physicochemical scaffold whose core aromatic catechol-based properties: electron transfer, metal chelation, self-assembly, and polymerization into semiconducting biopolymers have been repeatedly repurposed throughout three billion years, from prebiotic Earth to the human brain.

From its plausible origins in prebiotic catalysis, these properties were leveraged by life to solve recurring challenges in survival and protection (e.g., microbial siderophores, protective melanins), settlement and colonization (e.g., marine bioadhesives), and competitive/cooperative communication (e.g., allelochemicals, social signaling). This evolutionary history of DOPA reveals a consistent pattern, a conserved 'Stress-Motion-Motivation-Action’ arc that links environmental challenges to the emergence of goal-directed behavior. I propose that DOPA's same ancient chemical logic was not discarded but repurposed in the mammalian brain. Beyond serving as a dopamine precursor, DOPA's non-canonical functions: adhesion, chelation, and polymerization into the semiconducting biopolymer neuromelanin, form a multiscale biophysical scaffold. This scaffold provides the structural and electrochemical stability necessary for the neural circuits and for the canonical dopamine signaling to execute not only motivation and movement but also the agency-related complex computations. This model thus bridges molecular biophysics with higher-order cognition, reframing DOPA as a fundamental material substrate for cognitive agency.