Sk. Armstrong et al., Cross-referenced combinatorial libraries for the discovery of metal-complexing ligands: library deconvolution by LC-MS, ANALYST, 125(12), 2000, pp. 2206-2215
N-Acylthioureas are excellent ligands for a variety of heavy metals, but th
eir metal selectivity is highly dependent on the precise nature of the subs
tituents present. In this paper we show how combinatorial chemistry techniq
ues can be used to establish relative affinities for copper within a mixtur
e of 100 such thioureas. Following a straightforward synthesis, and copper
extraction using standard liquid-liquid extraction techniques, LC-MS was us
ed to identify the ligands which bind most strongly to the copper ions. Amo
ng the 100 ligands XC(O)N(Z)C(S)NHY, the most important substituent is the
Y group bound to the NH: only aromatic Y substituents give strong binding t
o copper. The acyl X substituents are invariably aromatic, and an electron-
rich X group is best; the affinity for copper seems to be less dependent on
the Z substituent, although a large group such as benzyl disfavours copper
binding. The five ligands from the library which bind copper most strongly
have been clearly identified by a series of experiments: they all have aro
matic groups in the Y position, but the X and Z substituents can be more va
ried. This is a very convincing demonstration of the power of combinatorial
methods: to have found the same information by conventional methods would
have required a lengthy and repetitive series of syntheses and investigatio
ns. In addition, our results give some preliminary evidence for synergistic
binding of two different ligands, but this requires further investigation.