Photoexcitation Dynamics of V-PYRRO/NO Investigated Using Femtosecond Time-Resolved Infrared Spectroscopy

Area of Science:

• Photochemistry
• Chemical Dynamics
• Medicinal Chemistry

Background:

• Diazeniumdiolates are nitric oxide (NO) donors, with protected variants enabling controlled NO delivery.
• Photoprotected diazeniumdiolates offer spatiotemporal NO release, crucial for targeted therapies.
• Understanding photodissociation mechanisms is key to developing effective photoactivated NO donors.

Purpose of the Study:

• To investigate the molecular-level photodissociation dynamics of photoprotected diazeniumdiolates.
• To elucidate the mechanism of NO release from V-PYRRO/NO upon photoexcitation.

Main Methods:

• Femtosecond spectroscopy was used to probe the real-time dynamics of photoexcited V-PYRRO/NO.
• Computational calculations of potential energy surfaces for excited states were performed.
• Direct observation and characterization of transient intermediates were achieved.

Main Results:

• Excitation at 305 nm induced ultrafast cleavage of the N═N bond in V-PYRRO/NO within 0.3 picoseconds.
• A transient oxynitrene intermediate (CH2═CHON) was directly observed in solution, forming in the singlet state.
• The oxynitrene rearranged to CH2═CHNO with a time constant of 16 ± 5 nanoseconds, confirmed by potential energy surface calculations.

Conclusions:

• The study reveals the detailed photodissociation pathway of a liver-selective NO prodrug, V-PYRRO/NO.
• The findings provide molecular insights into the unusual N═N bond breakage in photoprotected diazeniumdiolates.
• This knowledge can guide the rational design of improved photoactivated NO-releasing agents for therapeutic applications.