Spin‐Forbidden Excitation: A New Approach for Triggering Photopharmacological Processes with Low‐Intensity NIR Light

Exposure to low‐intensity radiation in the near‐infrared (NIR) spectral region matching the optically transparent “phototherapeutic window” of biological tissues can be applied to directly populate spin‐restricted excited states of light‐responsive compounds. This unconventional and unprecedented approach is introduced herein as a new strategy to overcome some of the major unresolved problems observed in the rapidly emerging fields of photopharmacology and molecular photomedicine, where practical applications in living cells and organisms are still limited by undesired side reactions and insufficient light penetration. Water‐soluble and biocompatible metal complexes with a significant degree of spin–orbit coupling were identified as target candidates for testing our new hypothesis. As a first example, a dark‐stable manganese carbonyl complex acting as a visible‐light‐triggered CO‐releasing molecule (Photo‐CORM) is shown to be photoactivated by NIR radiation, although apparently no spectroscopically evident absorption bands are detectable in this low‐energy region. This quite remarkable effect is ascribed to a strongly restricted, but obviously not completely forbidden optical population of the lowest triplet excited state manifold of the diamagnetic complex from the singlet ground state.