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Formation of a Metal-to-Nitrogen Bond of Normal Length by a Neutral Sufonamide Group within a Tridentate Ligand. A New Approach to Radiopharmaceutical Bioconjugation

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posted on 04.03.2013, 00:00 authored by Theshini Perera, Pramuditha Abhayawardhana, Patricia A. Marzilli, Frank R. Fronczek, Luigi G. Marzilli
We demonstrate that a tertiary sulfonamide group, N(SO2R)­R′2, can rehybridize to form a M–N bond of normal length even when the group is in a linear tridentate ligand, such as in the new tridentate N(SO2R)­dpa ligands derived from di-(2-picolyl)­amine (N(H)­dpa). N(SO2R)­dpa ligands were used to prepare fac-[Re­(CO)3(N(SO2R)­dpa)]­(PF6 or BF4) complexes. Structural characterization of the new complexes established that the tertiary sulfonamide nitrogen atom binds to Re with concomitant sp2-to-sp3 rehybridization, facilitating facial coordination. The new fac-[Re­(CO)3(N(SO2R)­dpa)]­X structures provide the only examples for any metal with the sulfonamide as part of a noncyclic linear tridentate ligand and with a normal metal-to-nitrogen­(tertiary sulfonamide) bond length. Rare previous examples of such normal M–N bonds have been found only in more constrained situations, such as with tripodal tetradentate ligands. Our long-term objectives for the new tridentate N(SO2R)­dpa ligands are to develop the fundamental chemistry relevant to the eventual use of the fac-[MI(CO)3]+ core (M = 99mTc, 186/188Re) in imaging and therapy. The sulfonamide group uniquely contributes to two of our goals: expanding ways to conjugate the fac-[MI(CO)3]+ core to biological molecules and also developing new symmetrical tridentate ligands that can coordinate facially to this core. Tests of our conjugation method, conducted by linking the fac-[ReI(CO)3]+ core to a new tetraarylporphyrin (T­(N(SO2C6H4)­dpa)­P) as well as to a dansyl (5-(dimethylamino)­naphthalene-1-sulfonyl) group, demonstrate that large molecular fragments can be tethered via a coordinated tertiary sulfonamide linkage to this core.

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