Relevance of the ligand exchange rate and mechanism of fac-[(CO)3M(H2O)3]+ (M = Mn, Tc, Re) complexes for new radiopharmaceuticals.

The water exchange process on fac-[(CO)3Mn(H2O)3]+ and fac-[(CO)3Tc(H2O)3]+ was kinetically investigated by 17O NMR as a function of the acidity, temperature, and pressure. Up to pH 6.3 and 4.4, respectively, the exchange rate is not affected by the acidity, thus demonstrating that the contribution of the monohydroxo species fac-[(CO)3M(OH)(H2O)2] is not significant, which correlates well with a higher pKa for these complexes compared to the homologue fac-[(CO)3Re(H2O)3]+ complex. The water exchange rate K298ex/s(-1) (DeltaHex double dagger/kJ mol(-1); DeltaSex double dagger/J mol(-1) K(-1); DeltaV double dagger/cm3 mol-1) decreases down group 7 from Mn to Tc and Re: 23 (72.5; +24.4; +7.1) > 0.49 (78.3; +11.7; +3.8) > 5.4 x 10(-3) (90.3; +14.5; -). For the Mn complex only, an O exchange on the carbonyl ligand could be measured (K338co = 4.3 x 10(-6) s(-1)), which is several orders of magnitude slower than the water exchange. In the case of the Tc complex, the coupling between 17O (I = 5/2) and 99Tc (I = 9/2) nuclear spins has been observed (1J99Tc,17O = 80 +/- 5 Hz). The substitution of water in fac-[(CO)3M(H2O)3]+ by dimethyl sulfide (DMS) is slightly faster than that by CH3CN: 3 times faster for Mn, 1.5 times faster for Tc, and 1.2 times faster for Re. The pressure dependence behavior is different for Mn and Re. For Mn, the change in volume to reach the transition state is always clearly positive (water exchange, CH3CN, DMS), indicating an Id mechanism. In the case of Re, an Id/Ia changeover is assigned on the basis of reaction profiles with a strong volume maximum for pyrazine and a minimum for DMS as the entering ligand.