This talk will focus on two C1-C5 cycloaromatization reactions enabled by the unique stereoelectronics of aromatic alkynes.<br/>The C1-C5 photocyclization of enediynes leads to four H-atom transfers from the environment and, thus, can be utilized for the design of efficient reagents for double-strand DNA photocleavage. The ratio of double- (ds) to single-strand (ss) DNA damage by hybrid molecules that combine enediynes with basic amino acids and peptides exceeds the ds:ss ratios provided by the natural enediynes, the most potent family of anticancer agents in Nature. Furthermore, the reactivity towards DNA and the ds:ss ratio are increased dramatically at the lower pH of hypoxic cancer tissues. This increase is based on the new photophysical approach to selective DNA photodamage based on pH-gated photoinduced electron transfer between an appropriately positioned amino group and the DNA-damaging “warhead”.<sup> </sup><br/>C1-C5 photocyclization of enynes was the last missing example of the four archetypical cycloaromatizations of enediynes and enynes. This process was discovered by combining a twisted alkene excited state with a new self-terminating path for intramolecular conversion of diradicals into closed-shell products. This cascade is interesting from the practical perspective since it leads to photorelease of formaldehyde and related carbonyl compounds.

Alkyne photochemistry for double DNA-cleavage and for the uncaging of aldehydes

255th National Meeting (2018)

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