Rational design of a dual-mode optical and chemical prodrug.
OBJECTIVE
The purpose of this study is to demonstrate the rational design and behaviour of the first dual-mode optical and chemical prodrug, exemplified by an acetyl salicylic acid-based system.


METHODS
A cyclic 1,4-benzodioxinone prodrug was synthesised by reaction of 3,5-dimethoxybenzoin and acetyl salicoyl chloride with pyridine. After purification by column chromatography and recrystallization, characterization was achieved using infrared and NMR spectroscopies, mass spectrometry, elemental analysis and single crystal X-ray diffraction. Light-triggered drug liberation was characterised via UV-visible spectroscopy following low-power 365 nm irradiation for controlled times. Chemical drug liberation was characterised via UV-visible spectroscopy in pH 5.5 solution.


RESULTS
The synthetic method yielded pure prodrug, with full supporting characterisation. Light-triggered drug liberation proceeded at a rate of 8.30x10(-2) s-1, while chemical, hydrolytic liberation proceeded independently at 1.89x10(-3) s-1. The photochemical and hydrolytic reactions were both quantitative.


CONCLUSIONS
This study demonstrates the first rational dual-mode optical and chemical prodrug, using acetyl salicylic acid as a model, acting as a paradigm for future dual-mode systems. Photochemical drug liberation proceeds 44 times faster than chemical liberation, suggesting potential use in drug-eluting medical devices where an additional burst of drug is required at the onset of infection.
McCoy
Colin P
CP
School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK. c.mccoy@qub.ac.uk
Rooney
Clare
C
Jones
David S
DS
Gorman
Sean P
SP
Nieuwenhuyzen
Mark
M
D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D018360:Crystallography, X-Ray; D015195:Drug Design; D006868:Hydrolysis; D007202:Indicators and Reagents; D008027:Light; D008958:Models, Molecular; D010777:Photochemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D011725:Pyridines / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D007202:Indicators and Reagents; D011355:Prodrugs; D011725:Pyridines; C023666:pyridine; D001241:Aspirin