Urocanic acid as an efficient hydroxyl radical scavenger: a quantum theoretical study

Area of Science:

• Computational Chemistry
• Biochemistry
• Dermatology

Background:

• Urocanic acid (UCA) in human epidermis functions as a natural sunscreen.
• UCA's trans-to-cis photoisomerization under UV-B radiation is linked to immunosuppression.
• Recent findings highlight UCA's antioxidant capacity as a hydroxyl radical scavenger.

Purpose of the Study:

• To investigate the reaction mechanisms of trans-urocanic acid (UCA) with hydroxyl radicals (OH·).
• To computationally model the stepwise addition of up to four OH· radicals to UCA.
• To compare the energy barriers of OH· radical addition with UCA's cis-trans isomerization.

Main Methods:

• Density Functional Theory (DFT) was used to optimize molecular geometries in the gas phase.
• Solvation effects were modeled using the polarizable continuum model (PCM).
• Second-order Møller-Plesset perturbation theory (MP2) and vibrational frequency analysis were employed.

Main Results:

• The initial binding of an OH· radical to UCA has a positive energy barrier.
• Subsequent reactions with OH· radicals are energetically favorable (exergonic).
• The energy barrier for the first OH· radical addition is comparable to UCA's cis-trans isomerization barrier.

Conclusions:

• Urocanic acid (UCA) demonstrates significant potential as an antioxidant by efficiently scavenging hydroxyl radicals.
• The comparable energy barriers suggest that radical scavenging and UV-induced isomerization can occur concurrently.
• These findings provide a deeper mechanistic understanding of UCA's dual role in skin photobiology.