TY - JOUR
T1 - The Role of Norrish Type-I Chemistry in Photoactive Drugs
T2 - An ab initio Study of a Cyclopropenone-Enediyne Drug Precursor
AU - Leger, Stephen J
AU - Marchetti, Barbara
AU - Ashfold, Michael N R
AU - Karsili, Tolga N V
PY - 2020/12/22
Y1 - 2020/12/22
N2 - We present a contemporary mechanistic description of the light-driven conversion of cyclopropenone containing enediyne (CPE) precusors to ring-opened species amenable to further Bergman cyclization and formation of stable biradical species that have been proposed for use in light-induced cancer treatment. The transformation is rationalized in terms of (purely singlet state) Norrish type-I chemistry, wherein photoinduced opening of one C–C bond in the cyclopropenone ring facilitates non-adiabatic coupling to high levels of the ground state, subsequent loss of CO and Bergman cyclization of the enediyne intermediate to the cytotoxic target biradical species. Limited investigations of substituent effects on the ensuing photochemistry serve to vindicate the experimental choices of Popik and coworkers (J. Org. Chem., 2005, 70, 1297–1305). Specifically, replacing the phenyl moiety in the chosen model CPE by a 1,4-benzoquinone unit leads to a stronger, red-shifted parent absorption, and increases the exoergicity of the parent → biradical conversion.
AB - We present a contemporary mechanistic description of the light-driven conversion of cyclopropenone containing enediyne (CPE) precusors to ring-opened species amenable to further Bergman cyclization and formation of stable biradical species that have been proposed for use in light-induced cancer treatment. The transformation is rationalized in terms of (purely singlet state) Norrish type-I chemistry, wherein photoinduced opening of one C–C bond in the cyclopropenone ring facilitates non-adiabatic coupling to high levels of the ground state, subsequent loss of CO and Bergman cyclization of the enediyne intermediate to the cytotoxic target biradical species. Limited investigations of substituent effects on the ensuing photochemistry serve to vindicate the experimental choices of Popik and coworkers (J. Org. Chem., 2005, 70, 1297–1305). Specifically, replacing the phenyl moiety in the chosen model CPE by a 1,4-benzoquinone unit leads to a stronger, red-shifted parent absorption, and increases the exoergicity of the parent → biradical conversion.
KW - photodissociation
KW - photostability
KW - photophysics
KW - photoactive drugs
KW - photochemistry
KW - physical organic chemistry
U2 - 10.3389/fchem.2020.596590
DO - 10.3389/fchem.2020.596590
M3 - Article (Academic Journal)
C2 - 33425854
VL - 8
JO - Frontiers in Chemistry
JF - Frontiers in Chemistry
SN - 2296-2646
M1 - 596590
ER -