Synthetic procedures for the preparation of fluorinated phosphonoacetic acid, HO2CCF2PO(OH)2, and its esters, RO2CCF2PO(OR')2, will be developed. The antiviral activity of these compounds will be tested and compared to the activity exhibited by phosphonoacetic acid, a compound which has previously been shown to have high antiviral activity towards herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, and related viruses. The fluorinated phosphonoacetic acid should be a stronger acid and consequently a better ligand than phosphonoacetic acid. Ionization constants and formation constants for complexes that form between fluorophosphonic acid and Ca, Mg, and Zn will be determined. NMR procedures and liquid chromatographic or the determination of fluorophosphonic acid and its esters will be developed. Both plaque assay and yield reduction assay will be employed to evaluate antiviral activity against herpes simplex type I and II virus, varicella-zoster virus, human cytomegalovirus, and murine cytomegalovirus.
