FK506 (tacrolimus) is a natural product now approved in the US and Japan for organ transplantation. FK506, in complex with its 12 kDa cytosolic receptor (FKBP12), is a potent agonist of immunosuppression through the inhibition of the phosphatase activity of calcineurin. Rapamycin (sirolimus), which is itself an immunosuppressant by a different mechanism, completes with FK506 for binding to FKBP12 and thereby acts as an antagonist of calcineurin inhibition. We have solved the X-ray structure of unliganded FKBP12 and of FKBP12 in complex with FK506 and with rapamycin; these structures show localized differences in conformation and mobility in those regions of the protein that are known, by site-directed mutagenesis, to be involved in calcineurin inhibition. A comparison of 16 additional X-ray structures of FKBP12 in complex with FKBP12-binding ligands, where those structures were determined from different crystal forms with distinct packing arrangements, lends significance to the observed structural variability and suggests that it represents an intrinsic functional characteristic of the protein. Similar differences have been observed for FKBP12 before, but were considered artifacts of crystal-packing interactions. We suggest that immunosuppressive ligands express their differential effects in part by modulating the conformation of FKBP12, in agreement with mutagenesis experiments on the protein, and not simply through differences in the ligand structures themselves.

Homoleptic silver(i) complexes [Ag(L-L),]BF, {L-L = RE(CH,),ER [R = Ph or Me, n = 2 or 3 ( E = S or Se), n = 3 ( E = Te)]} have been prepared and characterised by analysis, FAB mass spectrometry, and multinuclear N M R spectroscopy ('H, "Se, lZ5Te and lo9Ag). Variable-temperature N M R studies c = 10.339(3) 1 , U = 2075.7(7) A3 [from 28 values of

Homoleptic copper(I) and silver(I) complexes [M(n)(L-L)(2)(n)()](BF(4))(n)() (M = Cu or Ag; L-L = MeECH(2)EMe; E = S, Se or Te) have been prepared and characterized by analysis, FAB mass spectrometry, and IR and multinuclear NMR spectroscopy ((1)H, (77)Se, (125)Te, (63)Cu and (109)Ag). The single-crystal X-ray structures of [Cu(n)()(MeSeCH(2)SeMe)(2)(n)()](PF(6))(n)() (orthorhombic, P2(1)2(1)2(1), a = 10.879(7) Å, b = 16.073(7) Å, c = 9.19(1) Å, Z = 4) and [Ag(n)()(MeSeCH(2)SeMe)(2)(n)()](BF(4))(n)() (monoclinic, P2(1)/c, a = 14.546(9) Å, b = 14.65(1) Å, c = 30.203(9) Å, Z = 4) reveal extended three-dimensional cationic frameworks in the solid state which contain large cylindrical or rectangular channels accommodating the PF(6)(-) or BF(4)(-) counterions. In contrast, a single-crystal X-ray structure of [Cu(n)()(MeSCH(2)SMe)(2)(n)()](PF(6))(n)().nMeNO(2) (orthorhombic, Pbcn, a = 15.506(3) Å, b = 8.934(2) Å, c = 25.859(3) Å, Z = 8) shows tetrahedral Cu(I) ions coordinated to bridging dithioethers forming an cationic ribbon-like arrangement of 8-membered rings. Adjacent rings are linked by the Cu atoms. Variable temperature NMR studies have been used to probe various exchange processes occurring in solution in these systems.

have been prepared from [Cu(MeCN),]Y and L or L-L. The 63Cu and, where appropriate, 31P-{1H} NMR spectra, have been recorded from CH,CI, solutions of the complexes over the temperature range 300-1 75 K, including the first reported , , Cu resonances from arsenic and antimony donor ligand compounds. The effects of ligand size and geometry upon the , , Cu NMR spectra are discussed and typical copper chemicalshift ranges for Group 1 5 donor ligand compounds established. The structure of [Cu(cis-Ph,AsCH=CHAsPh,),] PF, has been esrablished by X-ray crystallography: orthorhombic, space group P2,2,2,, a = 14.775(6), b = 16.991 (5), c = 21.027(6) A, Z = 4. The copper atom is in a distorted tetrahedral environment [Cu-As 2.348(3)-2.358(3) A].

The X-ray structure of [Agn(PhSCH2CH&H2SPh)2,1"' shows an infinite array of tetrahedral Agl atoms coordinated via one S-donor of four distinct PhSCH2CH2CH2SPh ligands, whereas [Ag,(MeSCH2CH2CH2SMe),]n+ is a chain polymer involving trigonal (p2-S)2,S ligation with one S-donor bridging two adjacent Agl centres while the other S-donor of the dithioether ligand is non-bridging.