Oxidation of the antiviral drug acyclovir and its biodegradation product carboxy-acyclovir with ozone: kinetics and identification of oxidation products.
The oxidation of the antiviral drug acyclovir (ACV) and its main biotransformation product carboxy-acyclovir (carboxy-ACV) by ozone was investigated. Both compounds have recently been detected in surface water, and carboxy-ACV has also been detected in drinking water. The experiments revealed a strong pH dependence of the oxidation of ACV and carboxy-ACV with reaction rate constants increasing by 4 orders of magnitude between the protonated, positively charged form (k(ox,PH(+)), ∼2.5 × 10(2) M(-1) s(-1)) and the deprotonated, negatively charged form (k(ox,P(-)), 3.4 × 10(6) M(-1) s(-1)). At pH 8 a single oxidation product was formed which was identified via LC-LTQ-Orbitrap MS and NMR as N-(4-carbamoyl-2-imino-5-oxoimidazolidin)formamido-N-methoxyacetic acid (COFA). Using Vibrio fischeri , an acute bacterial toxicity was found for COFA while carboxy-ACV revealed no toxic effects. Ozonation experiments with guanine and guanosine at pH 8 led to the formation of the respective 2-imino-5-oxoimidazolidines, confirming that guanine derivatives such as carboxy-ACV are undergoing the same reactions during ozonation. Furthermore, COFA was detected in finished drinking water of a German waterworks after ozonation and subsequent activated carbon treatment.
Federal Institute of Hydrology (BfG), Koblenz, Germany.
Carsten
C
Prasse
Manfred
M
Wagner
Ralf
R
Schulz
Thomas A
TA
Ternes
D000212:Acyclovir / Q000737:chemistry* / Q000378:metabolism; D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism; D001711:Biotransformation; D006147:Guanine / Q000737:chemistry; D006151:Guanosine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010083:Oxidants, Photochemical / Q000737:chemistry*; D010084:Oxidation-Reduction; D010126:Ozone / Q000737:chemistry*; D012722:Sewage / Q000382:microbiology; D018508:Water Purification
D000998:Antiviral Agents; D010083:Oxidants, Photochemical; D012722:Sewage; D006151:Guanosine; D006147:Guanine; D010126:Ozone; D000212:Acyclovir