In particular, the invention relates to a substance or composition for use in the treatment of cancer, to the use of a substance or composition in the preparation of a medicament for the treatment of cancer, to a method of treating cancer, to a substance or composition for use in a method of sensitising cells to radiation, to the use of a substance or composition in the preparation of a medicament for use in sensitising cells to radiation, to a method of sensitising cells to radiation and to a metallocenyl ß diketone.

According to a first aspect of the invention there is provided a substance or composition for use in the treatment of cancer, the substance or composition including at least one compound selected from metallocenyl P-diketones of the general formula Mc-CO-CZ1Z2-CO-R in which Mc is selected from Fc (ferrocenyl), Rc (ruthenocenyl) and Oc (osmocenyl), R is H, alkyl or aryl and Z, and Z2 are independently H, alkyl, aryl or substituted alkyl, ferrocenyl, the enol forms of the P-diketones and metal complexes of the P-diketones of the general formula M (p- diketonato) A', M (P-diketonato) A'A2, M (i-diketonato) A'B'B2, M (ß- diketonato) B'B and M(ß-diketonato)B1B2B3B4 in which

M is selected from Rh and Ir, A1 and A2 are the same or different and are selected from cyclic dienes having 6-8 carbons, or linear alkenes having 2-7 carbons B', B2, B3 and B4 are the same or different and are selected from CO, P (R1R2R3), P (OR1) (OR2) (OR3), R4 and X in which R1,R2,R3 and R4 are the same or different and are independently selected from alkyl, phenyl and ferrocenyl, and X is a halide or a pseudohalide, and the method including the step of administering to a person or animal in need of treatment a therapeutically effective dose of the substance or composition.

Z1 and Z2 may be selected from haloalkyl and benzyl. R may be selected from CF3, CCI3, CH3, H, Ph (phenyl) and Mc. The halide may be F, Cl, Br or 1. The pseudohalide may be N3, NCO or SCN.

The compound may be selected from the group consisting of [M (i-diketonato) (cod)], [M (ß-diketonato) (CO) 2], [M (P- diketonato) (CO) (PR23)], [M (P-diketonato) {P-(OR2)3}2] [M(ß- diketonato) (CO) 2 (R3) (X)] or its acyl isomer [M (i-diketonato) (CO) (COR3) (X)], [M (P-diketonato) (CO) (PR23)(R3) (X)] or its acyl isomer [M (p- diketonato) (PR23) (COR3) (X)], [M (P-diketonato) {P-(OR2)3}2(R3)(X)] and [M (p- diketonato) (cod) (R3) (X)], in which M is Rh or Ir, cod is 1,5-cyclooctadiene, (ß- diketonato) is (McCOCHCOR) in which R is selected from CF3, Ceci3, CH3, H, phenyl and Mc, R2 is alkyl, phenyl, ferrocenyl and combinations thereof, R3 is alkyl, phenyl or ferrocenyl, and X is a halide or pseudohalide.

Preferred compounds in accordance with the invention are set out in the following compound list.

COMPOUND LIST (1) ferrocenoylacetaldehyde, (Hfch), (2) ferrocenoyltrichloroacetone, (Hfctca), (3) (#4-1,5-cyclooctadiene)(1-ferrocenyl-1,3-propanedionato-(4) K20, 0') rhodium (1), [Rh (FcH) (cod)], (4) (n4-1, 5-cyclooctadiene) (1,3-diferrocenyl-1,3- propanedionato-K20, 0') rhodium (1) [Rh (dfcm) (cod)], (5) (#4-1,5-cyclooctadiene)(1-ferrocenyl-3-phenyl-1, 3- propanedionato-#2O,O'(rhodium(1) [Rh(bfcm)(cod)], (6) (#4-1,5-cycloocadiene)(1-ferrocenyl-1,3-butanedionato- K20 0') rhodium (1), [Rh (fca) (cod) J, (7) (n4-1, 5-cyclooctadiene) (1-ferrocenyl-4, 4,4-trichloro-1,3- butanedionato-K20, 0') rhodium (1), [Rh (fctca) (cod)], (8) (#4-1,5-cyclooctadiene)(1-ferrocenyl-4, 4,4-trifluooro-1,3- butanedionato-#2O,O')rhodium(1), [Rh (fctfa) (cod)], (9) diferrocenoylmethane, (Hdfcm), (10) ferrocenoyltrifluoroacetone, (Hfctfa), (11) (#4-1, 5-cyclooctadiene) (1-ferrocenyl-4, 4,4-trifluoro-1,3- butanedionato-#2O, 0') iridium (1), [Ir (fctfa) (cod)], (12) (#4-1,5-cyclooctadiene)(1-ferrocenyl-1, 3-butanedionato- K'0, 0') iridium (1), [Ir (fca) (cod)], (13) (#4-1,5-cyclooctadiene)(1-ferrocenyl-3-phenyl-1, 3- propanedionato-#2O, 0') iridium (1), tir (bfcm) (cod)], (14) benzoylferrocenoylmethane, (Hbfcm), (15) ferrocenoylacetone, (Hfca), (16) (#4-1, 5-cyclooctadiene) (1-ferrocenyl-1, 3-propanedionato- #2O, 0') iridium (1), [Ir (fch) (cod)].

(17) (#4-1, 5-cyclooctadiene) (1-ruthenocenyl-1, 3- propanedionato-K20, 0') rhodium (1), [Rh (RcH) (cod)], (18) (n4-1, 5-cyclooctadiene) (1,3-diruthenocenyl-1,3- propanedionao-#2O, 0') rhodium (1) [Rh (drcm) (cod)], (19) (n4-1, 5-cyclooctadiene) (1-ruthenocenyl-3-phenyl-1, 3- propanedionato-#2o, 0') rhodium (1) [Rh (brcm) (cod)], (20) (#4-1, 5-cyclooctadiene) (1-ruthenocenyl-1, 3-butanedionato- #2O, 0') rhodium (1), [Rh (rca) (cod)], (21)(#4-1,5-cyclooctadiene)(1-ruthenocenyl-4, 4, 4-trichloro-1, 3- butanedionato-K20, 0') rhodium (1), [Rh (rctca) (cod)], (22) (#4-1,5-cyclooctadiene)(1-ruthenocenyl-4, 4,4-trifluooro- 1, 3-butanedionato-#2O, 0') rhodium (1), [Rh (rctfa) (cod)], (23) (#4-1, 5-cyclooctadiene) (1-osmocenyl-1, 3-propanedionato- K20, 0') rhodium (1), [Rh (OcH) (cod)], (24) (#4-1,5-cyclooctadiene) (1,3-diosmocenyl-1,3- propanedionato-K20, 0') rhodium (1) [Rh (docm) (cod)], (25) (#4-1,5-cyclooctadiene)(1-osmocenyl-3-phenyl-1, 3- propanedionato-#2O,O') rhodium (1) [Rh (bocm) (cod) l, (26) (#4-1, 5-cyclooctadiene) (1-osmocenyl-1, 3-butanedionato- K2O, 0') rhodium (1), [Rh (oca) (cod)], (27) (#4-1,5-cyclooctadiene)(1-osomocenyl-4,4,4-trichloro-1, 3- butanedionato-#2O, 0') rhodium (1), [Rh (octca) (cod)], (28) (#4-1,5-cyclooctadiene)(1-osmocenyl-4, 4, 4-trifluooro-1, 3- butanedionato-#2O,O')rhodim(1), [Rh(octfa)(cod)], (29) (#4-1,5-cyclooctadiene)(1-ferrocenyl-3-ruthenocenyl-1, 3- propanedionato-#2O,O') rhodium (1) [Rh (fcrcm) (cod)], (30) (#4-1, 5-cyclooctadiene) (1-ferrocenyl-3-osmocenyl-1, 3- propanedionato-#2O, 0') rhodium(1) [Rh(fcocm)(cod)],

(31) (#4-1,5-cyclooctadiene)(1-osmocenyl-3-ruthenocenyl-1, 3- propanedionato-K20, 0') rhodium (1) [Rh (ocrcm) (cod)], (32) (n4-1, 5-cyclooctadiene) (1,3-pentanedionato- K20 0') rhodium (1) [Rh (acac) (cod)], (33) 1-ruthenocenyl-1, 3-propanedione = HRcH, (34) 1, 3-diruthenocenyl-1, 3-propanedione = Hdrcm, (35) 1-ruthenocenyl-3-phenyl-1, 3-propanedione = Hbrcm, (36) ruthenocenoylacetone = 1-ruthenocenyl-1, 3-butanedione = Hrca, (37) ruthenocenoyltrichloroacetone = 1-ruthenocenyl-4, 4,4- trichloro-1, 3-butanedione = Hrctca, (38) ruthenocenoyltrifluoroacetone = 1-ruthenocenyl-4, 4,4- trifluoro-1, 3-butanedione = Hrctfa, (39) 1-osmocenyl-1, 3-propanedione = HOcH (40) 1, 3-diosmocenyl-1, 3-propanedione = Hdocm (41) 1-osmoceny)-3-phenyl-1, 3-propanedione = Hbocm, (42) osmocenoylacetone-1-osmocenyl-1, 3-butanedione = Hoca, (43) osmocenoyltrichloroacetone = 1-osmocenyl-4, 4,4- trichloro-1, 3-butanedione = Hoctca, (44)osmocenoyltrifluoroacetone = 1-osmocenyl-4,4,4-trifluoro- 1, 3-butanedione = Hoctfa, <BR> <BR> <BR> <BR> (45) ferrocenoyiosmocenoyimethane = 1 ferrocenyl-3- osmocenyl-1, 3-propanedione = Hfcocm, (46) osmocenoylruthenocenoylmethane 1-osmocenyl-3- ruthenocenyl-1, 3-propanedione = Hrcocm, (47) ferrocenoylruthenocenoylmethane = 1-ferrocenyl-3- ruthenocenyl-1, 3-propanedione = Hfcrcm,

(48) (#4-1, 5-cyclooctadiene)(1-ferrocenyl-3-ruthenocenyl-1, 3- propanedionato-#2O, 0') rhodium (1) [Rh (fcrcm) (cod)], (49) (n4-1, 5-cyclooctadiene) (1-ferrocenyl-3-osmocenyl-1, 3- propanedionato-#2O, O') rhodium (1) [Rh (fcocm) (cod)] Examples of compounds in accordance with the invention are set out in the Appendix.

According to another aspect of the invention there is provided the use of a substance or composition in the preparation of a medicament for the treatment of cancer, the substance or composition including at least one compound selected from metallocenyl (3-diketones of the general formula Mc- CO-CZ1,Z2-CO-R in which Mc is selected from Fc (ferrocenyl), Rc (ruthenocenyl) and Oc (osmocenyl), R is H, alkyl, haloalkyl or aryl and Z1 and Z2 are independently H, alkyl, aryl or substituted alkyl ferrocenyl, the enol forms of the (3-diketones and metal complexes of the P-diketones of the general formula M (P-diketonato) A', M (ß-diketonato) A1A2, M (ß- diketonato) A1B1B2, M (p-diketonato) B' 62 and M (ß-diketonato)B1B2B3B4 in which M is selected from Rh and Ir, A1 and A2 are the same or different and are selected from cyclic dienes having 6-8 carbons or linear alkenes having 2-7 carbons B1, B2, B3 and B4 are the same or different and are selected from CO, P (R1R2R3), P (OR') (OR2)(OR3), R4 and X in which R', R2, R3 and R4 are the same or different and are independently selected from alkyd, phenyl and ferrocenyl, and X is a halide or a pseudohalide.

Z1 and Z2 may be selected from haloalkyl and benzyl. R may be

selected from CF3, CCl3, CH3, H, Ph (phenyl) and Mc. The halide maybe selected from F, Cl, Br and 1. The pseudohalide may be selected from N3, NCO and SCN.

The compound may be selected from the group consisting of [M(ß-diketonato) (cod)], [M(ß-diketonato) (CO) 2], [M (ß- diketonato) (CO) (PR23)], [M (p-diketonato) {P-(OR2) 3} 2] [M (ß- diketonato) (CO) 2 (R3) (X)] or its acyl isomer, [M (a-diketonato) (CO) (COR3) (X)], [M (a-diketonato) (CO) (PR23)(R3)(X)] or its acyl isomer, [M (p- diketonato)(PR23)(COR3)(X)],[M(ß-diketonato){P-(OR2)3}2(R3) (X)] and [M(ß- diketonato)(cod)(R3)(X)], in which M is Rh or Ir, cod is 1,5-cyclooctadiene, (ß- diketonato) is (McCOCHCOR) in which R is selected from CF3, CC13, CH3, H, phenyl and Mc, R2 is alkyl, phenyl, ferrocenyl and combinations thereof, R3 is alkyl, phenyl or ferrocenyl, and X is a halide or pseudohalide.

Preferred compounds in accordance with the invention are set out in the Compound List.

According to another aspect of the invention there is provided a method of treating cancer, the method including the step of administering to a person or animal in need of treatment a therapeutically effective dose of a substance or composition which includes a compound selected from metallocenyl ß-diketon. es of the general formula Fc-CO-CZ1Z2-CO-R in which Mc is selected fro Fc (ferrocenyl), Rc (ruthenocenyl) and Oc (osmocenyl), R is H, alkyl, haloalkyl or aryl and Z, and Z2 are independently H, alkyl, aryl or substituted alkyl ferrocenyl, the enol forms of the P-diketones and metai complexes of the 0-diketones of the general formula M(ß-diketonato)A1, M(ß-diketonato)A1A2, M(ß-diketonato)A1B1B2,

M (P-diketonato) B'B2 and M (ß-diketonato)B1B2B3B4 in which M is selected from Rh and Ir, A1 and A2 are the same or different and are selected from cyclic dienes having 6-8 carbons or linear alkenes having 2-7 carbons B', B2, B3 and B4 are the same or different and are selected from CO, P (R1R2 R3), P (OR1) (OR2)(OR3), R4 and X in which R', R2, R3 and R4 are the same or different and are independently selected from alkyl, phenyl and ferrocenyl, and X is a halide or a pseudohalide.

Z, and Z2 may be selected from haloalkyl and benzyl. R may be selected from CF3, CCl3, CH3, H, Ph (phenyl) and Me. The halide may be F, Cl, Br or 1. The pseudohalide may be N3, NCO or SCN.

The compound may be selected from the group consisting of [M (i-diketonato) (cod)], [M (i-diketonato) (CO) 2], [M (p-diketonato) (CO) (PR23)], [M (ß-diketonato) {P-(OR2)3}2] [M (ß-diketonato) (CO) 2 (R3) (X)] oritsacyl isomer [M (p-diketonato) (CO) (COR3)(X)], [M (i-diketonato) (CO) (PR23) (R3) (X)] or its acyl isomer [M (ß-diketonato)(PR23)(COR3) (X)], [M (ß-diketonato) {P- (OR2) 3} 2 (R3) (X)] and [M (f3-diketonato) (cod) (R3) (X)], in which M is Rh or Ir, cod is 1,5-cyclooctadiene, (ß-diketonato) is (McCOCHCOR) in which R is selected from CF3, COg, CH3, H, phenyl and Mc, R2 is alkyl, phenyl, ferrocenyl and combinations thereof, R3 is alkyl, phenyl orferrocenyl, and X is a halide or pseudohalide.

Preferred compounds in accordance with the invention are set out in the Compound List.

The compounds of the invention are of particular use in the

treatment of a patient with cancer which has built up, or could build up, resistance to other therapeutical active substances. The compounds of the invention are also of particular use in the treatment of a patient with cancer which has built up, or could build up, resistance to radiotherapy, and can be administered before, together with or after radiotherapy.

According to another aspect of the invention there is provided a substance or composition for use in a method of sensitising cells to radiation, the substance of composition including a compound selected from metallocenyl-diketones of the general formula Mc-CO-CZ1Z2-CO-R in which Mc is selected from Fc (ferrocenyl), Rc (ruthenocenyl) and Oc (osmocenyl), R is H, alkyl, haloalkyl or aryl and Z1 and Z2 are independently H, alkyl, aryl or substituted alkyl ferrocenyl, the enol forms of the-diketones and metal complexes of the P-diketones of the general formula M(ß-diketonato)A1, M(ß-diketonato)A1A2, M (i-diketonato) A'B'B2, M (P-diketonato) B1B2 and M(ß-diketonato)B1B2B3B4 in which M is selected from Rh and Ir, A1 and A2 are the same or different and are selected from cyclic dienes having 6-8 carbons or linear alkenes having 2-7 carbons B1, B2, B3 and B4 are the same or different and are selected from CO, P (R1R2 R3), P (OR') (OR2)(OR3),R4 and X in which R', R2, R3 and R4 are the same or different and are independently selected from alkyl, phenyl and ferrocenyl, and X is a halide or a pseudohalide.

Z1 and Z2 may be selected from haloalkyl and benzyl. R may be selected from CF3, CCl3, CH3, H, Ph (phenyl) and Mc. The halide may be F, Cl, Br or 1. The pseudohalide may be N3, NCO or SCN.

The compound may be selected from the group consisting of M(ß-diketonato)(cod)], [M(ß-diketonato) (CO) 2], [M (p- diketonato) (CO) (PR23)], [M (ß-diketonato){-(OR2)3}2] [ diketonato) (CO) 2 (R3) (X)] or its acyl isomer [M (p-diketonato) (CO) (COR3) (X)], [M (p-diketonato) (CO) (PR23) (R3) (X)] or its acyl isomer [M (p- diketonato) (PR23) (COR3) (X)], [M (p-diketonato) {P-(OR2)3}2(R3) (X)] and [M (p- diketonato) (cod) (R3) (X)], in which M is Rh or Ir, cod is 1,5-cyclooctadiene, (p- diketonato) is (McCOCHCOR) in which R is selected from CF3, CCl3, CH3, H, phenyl and Mc, R2 is alkyl, phenyl, ferrocenyl and combinations thereof, R3 is alkyl, phenyl or ferrocenyl, and X is a halide or pseudohalide.

Preferred compounds in accordance with the invention are set out in the Compound List.

According to another aspect of the invention there is provided the use of a substance or composition in the preparation of a medicament for use in sensitising cells to radiation, the substance or composition including a compound selected from metallocenyl 0-diketones of the general formula Mc-CO-CZ1Z2-CO-R in which Mc is selected from Fc (ferrocenyl), Rc (ruthenocenyl) and Oc (osmocenyl), R is H, alkyl, haloalkyl or aryl and Za and Z2 are independently H, alkyl, aryl or substituted alkyl ferrocenyl, the envoi forms of the -diketones and metal complexes of the ß-diketones of the general formula M (P-diketonato) A', M (i-diketonato) A'A2, M (ß- diketonato)A1B1B2, M(ß-diketonato)B1B2 and M(ß-diketonato)B1B2B3B4 in which M is selected from Rh and Ir, A'and A2 are the same or different and are selected from cyclic dienes having 6-8 carbons or linear alkenes having 2-7 carbons

B1, B2, B3 and B4 are the same or different and are selected from CO, P (R1R2 R3), P (OR') (OR2)(OR3), R4 and X in which R1,R2,R3 and R4 are the same or different and are independently selected from alkyl, phenyl and ferrocenyl, and X is a halide or a pseudohalide.

Z, and Z2 may be selected from haloalkyl and benzyl. R may be selected from CF3, CCl3, CH3, H, Ph (phenyl) and Mc. The halide may be F, Cl, Br or 1. The pseudohalide may be N3, NCO or SCN.

The compound may be selected from the group consisting of [M (p-diketonato) (cod)], [M (p-diketonato) (CO) 2], [M (p- diketonato) (CO) (PR23)], [M(ß-diketonato){P-(OR2)3}2] [M (ß- diketonato) (CO) 2 (R3)(X)] or its acyl isomer [M (p-diketonato) (CO) (COR3) (X)], [M(ß-diketonato) (CO) (PR23) (R3) (X)] or its acyl isomer [M (p- diketonato) (PR23) (COR3) (X)], [M (i-diketonato) {P-(OR2)3}2(R3) (X)] and [M (ß- diketonato) (cod) (R3) (X)], in which M is Rh or Ir, cod is 1,5-cyclooctadiene, (ß- diketonato) is (McCOCHCOR) in which R is selected from CF3, CCI3, CH3, H, phenyl and Me, RI is alkyl, phenyl, ferrocenyl and combinations thereof, R3 is alkyl, phenyl or ferrocenyl, and X is a halide or pseudohalide.

Preferred compounds in accordance with the invention include (#4-1, 5-cycloctadiene) (1, 3-pentanedionato-#2O,O') rhodium (1) [Rh (acac) (cod)], and the compounds in the Compound List.

According to another aspect of the invention there is provided a method of sensitising cells to radiation, the method including the step of exposing the cells before, during or after irradiation, to a compound selected from metallocenyl ß-diketones of the general formula Mc-CO-CZ1Z2-CO-R in

which Mc is selected from Fc (ferroceny)), Rc (ruthenocenyl) and Oc (osmocenyl), R is H, alkyl, haloalkyl or awl and Z, and Z2 are independently H, alkyl, aryl or substituted alkyl ferrocenyl, the enol forms of the ß-diketones and metal complexes of the P-diketones of the general formula M (ß- diketonato) AI, M (ß-diketonato)A1A2, M(ß-diketonato)A1B1B2, M (ß- diketonato) B1B2 and M (ß-diketonato) B1B2B3B4 in which M is selected from Rh and Ir, A1 and A2 are the same or different and are selected from cyclic dienes having 6-8 carbons or linear alkenes having 2-7 carbons B1, B2, B3 and B4 are the same or different and are selected from CO, P (R1R2 R3), P(OR1)(OR2)(OR3), R4 and X in which R1, R2, R3 and R4 are the same or different and are independently selected from alkyl, phenyl and ferrocenyl, and X is a halide or a pseudohalide, and the method including the step of administering to a person or animal in need of treatment a therapeutically effective dose of the substance or composition.

Z1 and Z2 may be selected from haloalkyl and benzyl. R may be selected from CF3, CC13, CH3, H, Ph (phenyl) and Mc. The halide may be F, Cl, Br or 1. The pseudohalide may be N3, NCO or SCN.

The compound may be selected from the group consisting of [M(ß-diketonato) (cod)], [M ( (3-diketonato) (CO) 2], [M(ß- diketonato) (CO) (PR23)], [M (ß-diketonato)[P-(OR2)3}2] [M(ß- diketonato) (CO) 2 (R3) (X)] or its acyl isomer [M (ß-diketonato) (CO) (COR3)(X)], [M (P-diketonato) (CO) (PR23) (R3) (X)] or its acyl isomer [M (p- diketonato) (PR23)/(COR3)(X)], [M (ß-diketonato){P-(OR2)3} 2 (R3) (X)] and [M (p- diketonato) (cod) (R3) (X)], in which M is Rh or Ir, cod is 1,5-cyclooctadiene, (ß- diketonato) is (McCOCHCOR) in which R is selected from CF3, CC13, CH3,

H, phenyl and Mc, R2 is alkyl, phenyl, ferrocenyl and combinations thereof, R3 is alkyl, phenyl or ferrocenyl, and X is a halide or pseudohalide.

Preferred compounds in accordance with the invention include (n4-1, 5-cyclooctadiene) (1, 3-pentanedionato-#2O,O')rhodium(1) [Rh(acac)(cod)], and the compounds in the Compound List.

The substance or composition will, in particular, be used for sensitizing cells to radiation under hypoxic conditions.

According to another aspect of the invention there is provided a mètallocenyl-diketone of the general formula Mc-CO-CZ1Z2- CO-R in which Mc is selected from Fc (ferrocenyl), Rc (ruthenocenyl) and Oc (osmocenyl), R is H, alkyl or aryl and Z, and Z2 are independently H, alkyl, aryl or substituted alkyl, ferrocenyl, the enol forms of the diketones and metal complexes of the 0-diketones of the general formula M(ß-diketonato)A1, M(ß-diketonato)A1A2, M(ß-diketonato)A1B1B2, M(ß- diketonato) B1B2 and M (P-diketonato) B1B2B3B4 in which M is selected from Rh and Ir, A'and A2 are the same or different and are selected from cyclic dienes having 6-8 carbons, or linear alkenes having 2-7 carbons B1, B2, B3 and B4 are the same or different and are selected from CO, P (R1R2 R3), P (OR') (OR2) (OR3), R4 and X in which R', R2, R3and R4 are the same or different and are independently selected from alkyl, phenyl and ferrocenyl, and X is a halide or a pseudohalide, with the proviso that the compound may not be (1) ferrocenoyltrichloroacetone, (Hfctca),

(2) (#4-1, 5-cyclooctadiene) (1, 3-diferrocenyl-1 3- propanedionato-#2O,O')rhodium(1) [Rh (dfcm) (cod)], (3) (111-1, 5-cyclooctadiene) (1-ferrocenyl-3-phenyl-1, 3- propanedionato-K2O, 0') rhodium (1) [Rh (bfcm) (cod)], (4) (#4-1,5-cyclooctadiene)(1-ferrocenyl-1, 3-butanedionato- K2O, O') rhodium (1), [Rh (fca) (cod)], (5) (#4-1, 5-cyclooctadiene)(1-ferrocenyl-4, 4,4-trichloro-1,3- butanedionato-#2O, 0') rhodium (1), [Rh (fctca) (cod)], (6) (#4-1,5-cyclooctadiene)(1-ferrocenyl-4, 4,4-trifluooro-1,3- butanedionato-#2O, 0') rhodium (1), [Rh (fctfa) (cod)], (7) diferrocenoylmethane (Hdfcm), (8) ferrocenoyltrifluoroacetone, (Hfctfa), (9) benzoylferrocenoylmethane, (Hbfcm), (10) ferrocenoylacetone, (Hfca), (11) (#4-1,5-cyclooctadiene) (1,3-pentanedionato- K20, 0') rhodium (1) [Rh (acac) (cod)], Z, and Z2 may be selected from haloalkyl and benzyl. R may be selected from CF3, COg, CH3, H, Ph (phenyl) and Mc. The halide may be F, Cl, Br or I. The pseudohalide may be N3, NCO or SCN.

The compound may be selected from the group consisting of [M (p-diketonato) (cod)], [M (i-diketonato) (CO) 2], [M (ß- diketonato) (CO) (PR23)], [M(ß-diketonato){P-(OR2)3}2] [M diketonato)(CO)2(R3) (X)] or its acyl isomer [M (ß-diketonato) (CO) (COR3)(X)], [M (p-diketonato) (CO) (PR23) (R3) (X)] or its acyl isomer [M (, B- diketonato) (PR23) (COR3) (X)], [M (i-diketonato) {P-(OR203}2(R3)(X)] and [M (P- diketonato) (cod) (R3) (X)], in which M is Rh or Ir, cod is 1,5-cyclooctadiene, (ß-

diketonato) is (McCOCHCOR) in which R is selected from CF3, CCI3, CH3, H, phenyl and Mc, RI is alkyl, phenyl, ferrocenyl and combinations thereof, R3 is alkyl, phenyl orferrocenyf, and X is a halide or pseudohalide.

Preferred compounds are set out in the Compound List.

The invention is now described, by way of example, with reference to the accompanying Examples and the Figures in which Figure 1 is a graph showing the growth of various cancer cell lines and PHA-stimulated human lymphocytes as a function of Hfctfa concentration; Figure 2 is a graph of the growth of various cancer cell lines and PHA- stimulated human lymphocites as a function of [Rh (fctfa) (cod)] concentration ; Figure 3 is a graph of the growth of various cancer cell lines and PHA- stimulated human lymphocites as a function of the concentration of [Rh (fctca) (cod)] concentration; Figure 4 is a graph of survival fraction as a function of radiation dosage; Figure 5 is a graph of the survival fraction of CHO cells following irradiation under hypoxic conditions in the'presence of, uM [Rh (fctca) (cod)] as a function of radiation dosage; and Figure 6 is a graph of the survival fraction of CHO cells following irradiation under hypoxic conditions in the presence of, uM [Rh (fctfa) (cod)] as a function of radiation dosage; and The examples describe in vitro studies of metallocene- containing-diketones of the type Mc-CO-CH2CZ1Z2-CO-R in which Mc is as hereinbefore described R is CF3 (Hfctfa)], CCl3 (Hfctca), CH3 (Hfca), H (Hfch), Ph (Hbfcm) and Fc (Hdfcm) and their rhodium complexes Rh (ß-

diketonato) (cod), EXAMPLE 1 Effects offerrocene-containinc) p-diketones and their rhodium complexes on the growth of cancer cell lines In these experiments cancer cell lines were cultured in standard tissue culture medium supplemented with 10% fetal calf serum (FCS) at 37°C in an atmosphere of 5% CO2 in 96 well round bottom microtitre plates. The cultures were treated with either ferrocene-containing ß-diketones or their rhodium complexes at varying concentrations for 72 to 96h, and the extent of cell growth was assayed by MTT [3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] reactivity, which detects only viable cells.

The sensitivities of the two cancer cell lines HeLa, which is a sensitive human cervix epitheloid carcinoma cell line, and CoLo 320DM, which is an intrinsically multidrug resistant human colon adeno-carcinoma cell line, to 13 of the complexes of the invention was tested.

Eight of the more active complexes were also tested on the two cell lines COR L23, which is a sensitive human lung large cell carcinoma cell line, and COR L23/CPR, which is a variant of COR L23 and which is resistant to malphalan and other platinum compounds.

All the ferrocene-containing 0-diketones, as well as most of their rhodium-cod complexes inhibited the growth of all of the cancer cell lines tested, including those which are drug resistant, at concentrations

<1001lM (Table 1). The most active compound amongst the ferrocene complexes was Hfctfa (Table 1, Figure 1) whereas the two most active rhodium-ferrocene complexes were [Rh (fctfa) (cod)] and [Rh (fctca) (cod)] (Table 1, Figures 2 and 3) TABLE 1 Chemosensitivity of cancer cell lines and PHA-stimulated human lymphocytes to ferrocene, rhodium-ferrocene complexes and rhodium ruthenocene complexes IC 50 (p. M) * of the following cell lines for complexes Complexes HeLa CoLo COR COR PHA- 320DM L23 L23/CPR stimulated lympho- cytes Ferrocene: Hfch 73.4 80.8 Nd** Nd Nd Hfctca 37.7 28.4 12.5 20.1 67. 5 Hdfcm 54.4 64.3 75.4 74.4 >100 Hfctfa 6.8 7.3 4.5 6.3 83.1 Hbfcm 54.2 85.1 66.8 80.4 >100 Hfca 66.6 57.1 Nd Nd Nd Rhodium- Ferrocene: Rh (acac) (cod) 97.3 >100 Nd Nd Nd Rh (FcH) (cod) 62.4 35. 4 Nd Nd Nd Rh (dfcm) (cod) 18.4 70.8 19.9 30.8 42.2 Rh (bfcm) (cod) 28. 3 87.1 22.5 22.0 97.2 . Rh (fca) (cod) 64.4 56.6 Nd Nd Nd Rh (fctca) (cod) 7.9 3.0 1.3 2.0 4.7

Rh (fctfa) (cod) 12.5 13.4 8.5 5.8 41.6 [Rh (RcH) (cod)] 52.007 68. 803 33.973 39.615 [Rh (drcm) (cod)] NT NT NT NT [Rh (brcm) (cod)] 16.218 20.435 15.783 14.099 [Rh (rca) (cod)] 4.863 3 0.18 2.74 [Rh (rctca) (cod)] NT NT NT NT [Rh (rctfa) (cod)] 54.742 67.438 49.207 47.993 [Rh (fcrcm) (cod)] 17.125 29.207 10.101 20.108 * Data from 3-4 experiments are expressed as the mean drug concentration (µM)-causing 50% cell killing.

** not done EXAMPLE 2 Effects of ferroceneucontaininq ß-diketones and their rhodium complexes on the proliferation of human lymphocytes In these experiments suspensions of purified human mononuclear leukocytes were cultured in RPMI medium supplemented with 10% fetal calf serum (FCS) at 37°C in an atmosphere of 5% C02 in 96 well round bottom microtitre plates. To some of the wells a mitogen (phytohaemagglutinin, PHA) was added at a concentration of 2. 51lg/ml. The cultures were treated with either ferrocene-containing a-diketones or their rhodium complexes at varying concentrations for 72h, and the extent of cell growth was assayed by MTT reactivity.

The ferrocene complexes which were tested inhibited 50% of the growth of PHA-stimulated lymphocyte cultures only at concentrations of 67. 5µM and higher (Table 1). The lymphocyte cultures were, however, more sensitive to the rhodium-ferrocene complexes tested with [Rh (bfcm) (cod)] the least toxic to stimulated lymphocytes (Table 1).

The ideal anti-tumoragent should be an agent with high activity against cancer cells, including drug resistant cells, and low activity against stimulated normal human lymphocytes. Hfctfa possesses the highest tumor specificity and is eight times less active against normal human lymphocytes than tumor cells. This compound would therefore be a possible candidate for the treatment of various cancers, including multidrug resistant cancers.

Another possible candidate, [Rh (fctfa) (cod)], is 4-5 times more active against tumor cells than against stimulated human lymphocytes.

EXAMPLE 3 Effects of rhodium-ferrocene complexes on the survival of Chinese hamster ovary (CHO) cells after irradiation under aerobic and hypoxic conditions.

CHO cells were treated in glass test tubes with non-toxic concentrations (0.39pLM and 0.78ju. M) of the two rhodium-ferrocene complexes [Rh (fctca) (cod)] and [Rh (fctfa) (cod) J and irradiated with an 8 MV photon beam in a modular incubator chamber with a 2cm tissue equivalent wax buildup (8MV dmaX) under aerobic and hypoxic conditions. An oxygen enhancement ratio of 2.5 (Figure 4) was obtained indicating that the method used to establish a hypoxic cellular environment was highly effective.

Neither of the two rhodium complexes tested increased the sensitivity of CHO cells to irradiation in an aerobic environment (results not shown). However, both complexes increased the sensitivity of CHO cells under hypoxic conditions (Figures 4 and 5). A dose-modifying factor of 2.9 was obtained under hypoxic conditions for 0.78p. M [Rh (fctfa) (cod)] (Table 2)

and 1.9 for 0.39plM [Rh (fctca) (cod)] (Table 3). The dose-modifying factors were calculated as the ratio of mean inactivation doses [calculated from the respective inactivation parameters obtained from the linear quadratic fit of the cell growth fraction (S)]. Published dose modifying factors (DMFs) measured for cisplatin range from 1.2-2 (ChibberR, Stratford IJ, ONeill P, Sheldon PW, Ahmed I, Lee B. 1985. The interaction between radiation and complexes of cis-Pt (II) and Rh (II): Studied at the molecular level. Int J Radiat Biol 48 : 513-524 ; Van De Vaart,. PJM, Klaren, HM, Hofland/, Begg AC. 1997.

Oral platinum analogue JM216, a radiosensifizer in oxic murine cells. Int J Radiat Biol 72 (6) : 675-683).

These results demonstrate that the two rhodium-ferrocene complexes, [Rh (fctfa) (cod)] and [Rh (fctca) (cod)] compare favorably with cisplatin as inducers of hypoxia selective radiosensitization in rapidly proliferating CHO cells at submicromolar concentrations, suggesting that these complexes may be clinically useful in combination with radiation in the treatment of cancers. Initial tests with Hfctfa and Hfctca were also promising.

TABLE 2 Mean inactivation doses calculated from the response of Chinese hamster ovary cells following treatment with radiation and/or different concentrations of [Rh (fctfa) (cod)] under hypoxic conditions.

Dose modifying factors are stated as the ratio of mean inactivation doses.

Treatment Mean Inactivation Dose Dose (Gy) Modifying Factor (DMF) Radiation (Hypoxia) 6.44 Rh (fctfa) (cod) 0.391lM 2.41 2.6 Rh (fctfa) (cod) 0.78pM 2.19 2.9 TABLE 3 Mean inactivation doses calculated from the response of Chinese hamster ovary cells following treatment with radiation and/or different concentrations of [Rh (fctca) (cod)] under hypoxic conditions. Dose modifying factors are stated as the ratio of mean inactivation doses.

Treatment Mean Inactivation Dose Dose Modifying (Gy) Factor (DMF) Radiation 7.16 (Hypoxia) Rh (fctca) (cod) 3.73 1.9 0. 39µM Rh (fctca) (cod) 4.46 1.6 0.781lM EXAMPLE 4 SYNTHESIS OF THE METALLOCENE COMPOUNDS The synthesis of the new ferrocene-containing, ruthenocene- containing and osmocene-containing betadiketones can all be achieved by

Claisen condensation of acetylferrocene, acetylruthenocene or acetylosmocene with the appropriate ester under the influence of lithium diisopropylamide. A selected example of each of these classes of compounds is set out below. Co-ordination with rhodium is also demonstrated Betadiketone synthesis The ferrocene series : The synthesis of 1-ferrocenyl-1, 3-propanedione, HFcH To an ice-cool solution of acetylferrocene (2.28 g, 10 mmol) in dry, air free THF (18 ml) was added under nitrogen 5.5 ml of a 2.0 mol dm~3 THF solution of lithium diisopropyl amide. Stirring continued for 20 minutes during which time a brick red precipitate formed. A solution of dry, cold methyl formiate (0.6 g, 10 mmol) in THF (1 ml) was then added and stirring continued overnight. After 16 hours, diethyl ether (15 ml) was added to the reaction mixture, the precipitate filtered, washed with ether and air dried. The precipitate was then suspended in 0.5 mol dm'3 HCI and extracted with ether, the ether extracts dried with MgSO4, and the solvent removed to liberate HFcH in 35 yield. The crude product can be crystallised from hexane/ether (1: 1).

The ruthenocene series: The synthesis of 1-ruthenocenyl-1, 3- butanedione, Hrca.

To an ice-cool solution of acetylruthenocene (0. 6 g, 2.2 mmol) in dry, air free THF (4 ml) was added under nitrogen 1.1 ml of a 1.6 mol dm-3 THF

solution of lithium diisopropyl amide. Stirring continued for 20 minutes during which time a cream precipitate formed. A solution of dry ethyl acetate (x ml, 2.2 mmol) in THF (1 ml) was then added and stirring continued overnight. After 1 6 hours, diethyl ether (15 ml) was added to the reaction mixture, the precipitate filtered, washed with ether and air dried. The precipitate was then suspended in 0.5 mol dm-3 HCI and extracted with ether, the ether extracts dried with MgS04, and the solvent removed to liberate Hrca in 30-40% yield. The crude product can be purified further by column chromatography on Kieselgel utilising ether/hexane (3: 2) as eluent.

The osmocene series: The synthesis 1-osmocenyl-4, 4,4-trifluoro-1,3- butanedione, Hoctfa.

To an ice-cool solution of acetylosmocene (0.25 g, 0.69 mmol) in dry, air free THF (1 ml) was added under nitrogen 0. 35 ml of a 2 mot dm~3 THF solution of lithium diisopropyl amide. Stirring continued for 20 minutes during which time a cream precipitate formed. A solution of dry ethyl trifluoroacetate (0.1 g, 0.69 mmol) in THF (0.6 mi) was then added and stirring continued overnight. After 1 6 hours, diethyl ether (10 ml) was added to the reaction mixture, the precipitate filtered, washed with ether and air dried. The precipitate was then suspended in 0.5 mol dm~3 HCI and extracted with ether, the ether extracts dried with MgS04, and the solvent removed to liberate Hoctfa in 30 % yield. The crude product can be crystallised from hexane/ether (1: 1).

The mixed metallocene series: The synthesis of 1-ferrocenyl-3- ruthenocenylpropanedianato, Hfcrcm.

To an ice-cool solution of acetylruthenocene (0. 6 g, 2.2 mmol) in dry, air free THF (5 ml) was added under nitrogen 1.1 ml of a 2.0 mol dm-3 THF solution of lithium diisopropyl amide. Stirring continued for 20 minutes during which time a cream precipitate formed. A solution of dry methyl ferrocenoate (0.537 g, 2.2 mmol) in THF (1 ml) was then added and stirring continued overnight. After 1 6 hours, diethyl ether (15 mi) was added to the reaction mixture, the precipitate filtered, washed with ether and air dried. The precipitate was then suspended in 0.5 mol dm-3 HCl and extracted with ether, the ether extracts dried with MgSO4, and the solvent removed to liberate Hfcrcm in 30-40% yield. The crude product can be purified further by column chromatography on Kieselgel utilising ether/hexane (3: 2) as eluent.

Rhodium co-ordination The synthesis of (n4-1, 5-cyclooctadiene) (1-ferrocenyl-1, 3-propanedionato- #2O,O') rhodium (I), [Rh (FcH) (cod)].

To a stirred solution of [Rh2Cl2(cod)2] (0.5g, 1 mmol) in 6 ml DMF was added 1-ferrocenyl-1, 3-propanedione (0.512 g, 2 mmol). After 5 minutes, the crude product was precipitated with an excess of water, filtered and dissolved in ether. The ether solution was washed with water, dried with magnesium sulphate. After solvent removal the residue was crystallised from cold ether/hexane mixtures starting with a ratio of 1: 1. Pure crystals of [Rh (FcH) (cod) l were filtered in 65% yield from the mother liquor.

The synthesis of (n4-1, 5-cyclooctadiene) (1-ruthenocenyl-1, 3-

butanedionato-K2O, O) rhodium (l), [Rh (rca) (cod)] To a stirred solution of [Rh2Cl2(cod)2] (0.5g, 1 mmol) in 6 ml DMF was added 1-ruthenocenyl-1, 3-butanedione (0.631 g, 2 mmol). After 5 minutes, the crude product was precipitated with an excess of water, filtered and dissolved in ether. The ether solution was washed with water, dried with magnesium sulphate and the solvent removed. The crude product was then crystallised from cold ether/hexane mixtures starting with a ratio of 1: 1. Pure crystals of [Rh (rca) (cod)] were filtered in 75% yield from the mother liquor.

The synthesis of (n4-1, 5-cyclo octa diene) (1-osmocenyl-4, 4,4-trifluoro-1,3- propanedionato-K2O, O')) rhodium(I), [Rh(octfa)(cod)] To a stirred solution of [Rh2Cl2(cod)2] (0.5g, 1 mmol) in 6 mi DMF was added 1-osmocenyl-4, 4,4-trifluoro-1,3-butanedione (0. 917 g, 2 mmol).

After 5 minutes, the crude product was precipitated with an excess of water, filtered and dissolved in ether. The ether solution was washed with water, dried with magnesium sulphate. After solvent removal, the residue was crystallised from cold ether/hexane mixtures starting with a ratio of 1: 1. Pure crystals of [Rh (octfa) (cod)] were filtered in 55% yield from the mother liquor.

The synthesis of (n4-1, 5-cyclooctadiene) (1-ferrocenyl-3-ruthenocenyl-1, 3- propanedionato-#2O,O')rhodium(I), [Rh(fcrcm)(cod)] To a stirred solution of [Rh2Cl2(cod)2] (0.5g, 1 mmol) in 6 ml DMF was added 1-ferrocenyl-1, 3-propanedione (0. 97 9, 2 mmol). After 5 minutes,

the crude product was precipitated with an excess of water, filtered and dissolved in ether. The ether solution was washed with water, dried with magnesium sulphate and the crude product crystallised after solvent removal from cold ether/hexane mixtures starting with a ratio of 1: 1.

Pure crystals of [Rh (fcrcm) (cod)] were obtained in 65% yield from the mother liquor.

DISCUSSION Cisplatin is one of the most widely used drugs for the chemotherapy of cancer (Muggia FM. 1991 ; Introduction : Cisplatin update. Seminars in Oncology 18:1-4). However, this compound has serious side effects including nausea, vomiting and nephrotoxicity (Rosenberg B. 1985 ; Fundamental, studies with cisplatin. Cancer 55 : 2303-2316J all of which are dose limiting. The search for novel organometallic complexes exhib. iting higher anttneoplastic activity and decreased side-effects, has stimulated the interest of several investigators and many reports are available on the antineoplastic activity of transitional metal complexes. Among them some rhodium complexes appear to be promising antitumor agents (Bear JL, Gray HB, Rainen L, Chang I-M, Howard R, Serio G, Kimball AP. 1975. Interaction of Rhodium <BR> <BR> <BR> II carboxylates with molecules of biologic importance ; Cancer Chemother<BR> <BR> <BR> <BR> <BR> Rep 59 : 611-620o Fiamiani V, Ainis T, Cavallaro A, Piraino P. 1990 ; Antitumor effects of the new rhodium (II) complex: Rh2(Form)2(O2CCF3) 2(H2O)2 (Form = N,N'-di-p-tolylformamidinate ; J Chemother 2 : 319- 326. Sartori R, Rencoret G, Rencoret G, Mora A, Perez C, Pastene R, Sariego R, Moya SA. 1997 ; The novel use of Rh (I) complexes with <BR> <BR> <BR> naphthyridine ligands and poly (oxyethyleneJ as antitumorals. Anti-Cancer

Drugs 6 : 87-92J Some of these rhodium complexes, despite the heavy- metal character of rhodium, seem to show no nephrotoxicity (Kopf-Maier P. 1994. Complexes of metals other than platinum as antitumoral agents.

Eur J Clin Pharmacol 47 : 1-16 ; Craciunescu DG, Scaria V, Furlani A, Papaionnou A, Iglesias EP, Alonso MP 1991 Pharmacological and toxicological studies on new Rh (I) organometalic complexes. In Vivo 5. 329-332).

The presence of hypoxic cells, resistant to radiotherapy as a consequence of the rapid metabolism of oxygen in tumor tissue, is a limiting factor in the successful treatment of tumors by radiation.' Sensitization of radioresistant tumors can be achieved by the use of chemical radiosensitizers in combination with conventional radiotherapy.

The Applicant has found that metallocene-containing p- diketones of the type Mc-CO-CH2-CO-R in which Mc is selected from Fc (ferrocenyl), Rc (ruthenocenyl) and Oc (osmocenyl), and R is CF3, CCl3, CH3, H, Ph (phenyl) or Fc, the enol forms of the P-diketones and rhodium and iridium complexes of the 0-diketones previously untested in biological systems inhibit the growth of various cancer cells, including platinum resistant strains and multidrug resistant cancer cells. Furthermore, some of these complexes have also been found to sensitize cells to radiation under hypoxic conditions.

The synthesis of Fc-CO-CH2-CO-R, in which R is CF3, CFl3, CH3 Ph and Fc, as well as Rh (i-diketonato) (cod) has been described (Du Plessis WC, Vosloo TG, Swarts JC, 1998; ß-Diketones containing a <BR> <BR> <BR> ferrocenyl group : synthesis, structural aspects, pKa'values, group

electronegativities and complexation with rhodium(I). Dalton Trans., 2507-2514). The published route to the complexes involves at least five intermediates. The Applicant has also found that none of these intermediates, which include ferrocene itself, acetyl ferrocene, esters of the type R4COOMe and R4COOEt (R4 = Fc, CF3, CCI3, CH3, H, Ph or Fc), RhCl3 and [RhCl (cod)] 2, exhibit any significant anticancer activity. The Applicant has found that the compounds of the invention show better chemotherapeutic and radiosensitisation properties than cisplatin.

APPENDIX (i) 0 0 (ii) Fc (ferrocene) = Fe I Fc H 1. (i) The molecular structure of Ferrocenoylacetaldehyde, (Hfch). (ii) Fc refers to ferrocenyl = FeC10H9 = Fe(C5H5)(C5H4), a dicyclopentadienyl moiety.

2. The molecular structure of Ferrocenoyitrichloroacetone, (Hfctca). (ii) The molecular structure of cyclooctadiene (cod).

A = acetylacetonato or 1,3-pentanedionato or acac 3. (i) The molecular structure of (n4-1, 5-cyclooctadiene) (1,3- pentanedionato-K20, 0') rhodium (1) [Rh (acac) (cod)]. (ii) The molecular structure of cyclooctadiene (cod).

B = 1-ferrocenyl-1, 3-propanedionato or FcH 4. The molecular structure of (#4-1,5-cyclooctadiene) (1- ferrocenyl-1, 3-propanedionato-K2O,O') rhodium (1) [Rh (FcH) (cod) L C = 1,3-diferroncenyl-1,3-propanedianato or dfcm 5. The molecular structure of (#4-1, 5-cyclooctadiene) (1,3- diferrocenyl-1, 3-propanedionato-K2O, O') rhod ium (1) [Rh (df cm) (cod)].

D = 1-ferrocenyl-3-phenyl-1,3-propanedionato or bfcm 6. The molecular structure of (#4-1,5-cyclooctadiene) (1- ferrocenyl-3-phenyl-1, 3-propanedionato-K2O,O') rhodium (1) [Rh (bfcm) (cod)].

E = ferrocenyolyacetonato or 1-ferrocenyl-1, 3-butanedionato or fca 7. The molecular structure of (#4-1, 5-cyclooctadiene) (1- ferrocenyl-1, 3-butanedionato-K2O, 0') rhodium (1) [Rh (fca) (cod)].

F = ferrocenoyltrichloroacetonato or 1-ferrocenyl-4, 4,4-trichloro-1,3- butanedionato or fctca 8. The molecular structure of (rl4-l, 5-cyclooctadiene) (1- ferrocenyl-4, 4, 4-trichloro-1,3-butanedionato-K2O,O') rhodium (1) [Rh(fctfa)(cod)].

G = ferrocenoyltrifluoroacetonato or 1-ferrocenyl-4,4,4-trifluoro-1,3- butanedionate or fctfa 9. The molecular structure of (#4-1,5-cyclooctadiene) (1- ferrocenyl-4, 4,4-trifluooro-1, 3-butanedionato- K20, 0') rhodium (1) [Rh (fctfa) (cod)].

10. In all cases Fc in the above structures can be replaced by Rc (ruthenocenyl[Ru(C5H5)(C5H4)] or Oc (osmocenyl) [Os(C5H5)(C5H4)].