31 P NMR Evidence for Peroxide Intermediates in Lipid Emulsion Photooxidations: Phosphine Substituent Effects in Trapping.

Abstract

Intralipid is a lipid emulsion used in photodynamic therapy (PDT) for its light scattering and tissue-simulating properties. The purpose of this study is to determine whether or not Intralipid undergoes photooxidation, and we have carried out an Intralipid peroxide trapping study using a series of phosphines [2'-dicyclohexylphosphino-2,6-dimethoxy-1,1'-biphenyl-3-sulfonate, 3-(diphenylphosphino)benzenesulfonate, triphenylphosphine-3,3',3''-trisulfonate and triphenylphosphine]. Our new findings are as follows: (1) An oxygen atom is transferred from Intralipid peroxide to the phosphine traps in the dark, after the photooxidation of Intralipid. 3-(Diphenylphosphino)benzenesulfonate is the most suitable trap in the series owing to a balance of nucleophilicity and water solubility. (2) Phosphine trapping and monitoring by 31 P NMR are effective in quantifying the peroxides in H2 O. An advantage of the technique is that peroxides are detected in H2 O; deuterated NMR solvents are not required. (3) The percent yield of the peroxides increased linearly with the increase in fluence from 45 to 180 J cm-2 based on our trapping experiments. (4) The photooxidation yields quantitated by the phosphines and 31 P NMR are supported by the direct 1 H NMR detection using deuterated NMR solvents. These data provide the first steps in the development of Intralipid peroxide quantitation after PDT using phosphine trapping and 31 P NMR spectroscopy.