The reactions of serum albumin, a blood carrier of gold(I), with the auranofin analogue triisopropylphosphine(2,3,4,6-tetra-Q-acetyl-1-thio-beta-D-glucopyranosato-S)gold(I) (i-Pr3PAuSATg) and free triisopropylphosphine have been studied in buffered aqueous solution using {H-1}P-31 NMR and chromatographic methods. Triisopropylphosphine (i-Pr3P) is oxidized to i-Pr3PS Via an albuminthiolatotriisopropylphosphonium ion, i-Pr3p+SCH2(HSCH2)Alb, which is formed by attack on a protein disulfide bond. This species is the key intermediate in the albumin-driven conversion of a phosphine ligand (e.g., from auranofin or an analogue) into phosphine oxide or phosphine sulfide. i-Pr3p+SCH2-(HSCH2)Alb, which is characterized by a P-31 NMR chemical shift of 75.4 ppm, forms quickly and then reacts slowly (k(obs) = (6.9 +/- 0.6) x 10(-5) s-1) to form i-Pr3PS and a small quantity of i-Pr3PO. The auranofin analogues i-Pr3PAuSATg and i-Pr3PAuCl, react with serum albumin at cysteine-34 to form AlbSAuPi-Pr3 via displacement of the anions. i-Pr3PAuCl reacts further at weak binding sites analogous to the histidine binding sites of auranofin. In contrast to the displacement of Et3P from AlbSAuPEt3 by thiols, cyanide is required to displace i-Pr3P from AlbSAuPi-Pr3. The liberated i-Pr3P also reacts via the alubminphosphonium intermediate described above to form i-P3PS and traces of i-P3PO. In order to interpret the protein studies, a variety of potential reaction products (i-Pr3PAuX, X = CN, ATgS, Cl; i-Pr3PY, Y = O, S) were prepared and characterized by P-31 NMR spectroscopy. Model reactions of i-Pr3PAuX (X = Cl, ATgS) with cyanide are also reported.