Competing Photocleavage on Boron and at the <i>meso</i>-Position in BODIPY Photocages

BODIPY photocages (photocleavable protective groups) have stirred interest because they can release biologically active cargo upon visible light excitation. We conducted combined theoretical and experimental investigations on selected BODIPY photocages to elucidate the mechanism of the competing photocleavage at the boron and <i>meso</i>-position. Based on the computations, the former reaction involves elongation of the B-C bond, yielding a tight borenium cation and methyl anion. These ions are intercepted by CH₃OH, enabling an efficient proton-coupled electron transfer (PCET) to produce the methane and isolated ether photoproducts. Singlet and triplet excited-state lifetimes were measured in CH₃OH and CD₃OD to probe the kinetic isotope effects (KIEs). The resulting KIEs are small, implying that the kinetic bottleneck is due to the C-B bond scission rather than the subsequent PCET. The introduction of a methoxy group in the <i>meso</i>-phenoxy substituent redirects the photosubstitution toward the <i>meso</i>-position. The corresponding regiochemistry was explained computationally. On elongating the C-O bonds in the S₁ state, it is found that the unproductive conical intersection is encountered much earlier for the alkyl-O bond than for the phenyl-O bond. The current findings are valuable for the rational design of new BODIPY photocages with tailored biological applications.