Charlotte Vale

Could quantum biology provide the tools to cope with tuberculosis, a disease which affects about 10 million in the world today and kills about 1.5 million of them annually?

Spin physics is central to the radical pair mechanism of the avian compass and is probably the fastest growing field within quantum biology.

Isoniazid (isonicotinylhydrazide, INH) is a key antibiotic used in the treatment of tuberculosis (TB). It is a prodrug that inhibits the formation of the mycobacterial cell wall by inhibiting the synthesis of mycolic acids. Isoniazid must be activated by KatG, a bacterial catalase-peroxidase enzyme in Mycobacterium tuberculosis and other bacteria.

The precise reaction mechanism remains controversial and may involve the formation of a radical pair intermediate. The large 13 C hyperfine coupling of the substituted [acyl-13C]-INH radical is expected to enhance the singlet-triplet interconversion rate of this radical pair by allowing simultaneous electronic and nuclear spin 'flips' in the isoniazid derived radical, thereby enhancing the formation of the INA-NAD adduct.

The aims of this project are to identify possible spin dependent reaction pathways, build and refine in silico models of the spin dynamics of INH action (e.g. based on the radical pair mechanism), and generate predictions and suggest protocol to detection of the effects of isotopic substitution, static magnetic field effects, and possibly oscillatory magnetic field effects that may be tested in the experimental project.