Linear Bidentate Ligands (L) with Two Terminal Pyridyl N-Donor Groups Forming Pt(II)LCl₂ Complexes with Rare Eight-Membered Chelate Rings

Abstract

NMR and X-ray diffraction studies were conducted on Pt­(II)­LCl2 complexes prepared with the new N-donor ligands N(SO2R)­Me n dpa (R = Me, Tol; n = 2, 4). These ligands differ from N(H)­dpa (di-2-picolylamine) in having the central N within a tertiary sulfonamide group instead of a secondary amine group and having Me groups at the 6,6′-positions (n = 2) or 3,3′,5,5′-positions (n = 4) of the pyridyl rings. The N(SO2R)­3,3′,5,5′-Me4dpa ligands are coordinated in a bidentate fashion in Pt­(N(SO2R)­3,3′,5,5′-Me4dpa)­Cl2 complexes, forming a rare eight-membered chelate ring. The sulfonamide N atom did not bind to Pt­(II), consistent with indications in the literature that tertiary sulfonamides are unlikely to anchor two meridionally coordinated five-membered chelate rings in solutions of coordinating solvents. The N(SO2R)­6,6′-Me2dpa ligands coordinate in a monodentate fashion to form the binuclear complexes [trans-Pt­(DMSO)­Cl2]2(N(SO2R)­6,6′-Me2dpa). The monodentate instead of bidentate N(SO2R)­6,6′-Me2dpa coordination is attributed to 6,6′-Me steric bulk. These binuclear complexes are indefinitely stable in DMF-d 7, but in DMSO-d 6 the N(SO2R)­6,6′-Me2dpa ligands dissociate completely. In DMSO-d 6, the bidentate ligands in Pt­(N(SO2R)­3,3′,5,5′-Me4dpa)­Cl2 complexes also dissociate, but incompletely; these complexes provide rare examples of association–dissociation equilibria of N,N bidentate ligands in Pt­(II) chemistry. Like typical cis-PtLCl2 complexes, the Pt­(N(SO2R)­3,3′,5,5′-Me4dpa)­Cl2 complexes undergo monosolvolysis in DMSO-d 6 to form the [Pt­(N(SO2R)­3,3′,5,5′-Me4dpa)­(DMSO-d 6)­Cl]+ cations. However, unlike typical cis-PtLCl2 complexes, the Pt­(N(SO2R)­3,3′,5,5′-Me4dpa)­Cl2 complexes surprisingly do not react readily with the excellent N-donor bioligand guanosine. A comparison of the structural features of over 50 known relevant Pt­(II) complexes having smaller chelate rings with those of the very few relevant Pt­(II) complexes having eight-membered chelate rings indicates that the pyridyl rings in Pt­(N(SO2R)­3,3′,5,5′-Me4dpa)­Cl2 complexes are well positioned to form strong Pt–N bonds. Therefore, the dissociation of the bidentate ligand and the poor biomolecule reactivity of the Pt­(N(SO2R)­3,3′,5,5′-Me4dpa)­Cl2 complexes arise from steric consequences imposed by the −CH2–N­(SO2R)–CH2– chain in the eight-membered chelate ring.

Synthesis, characterization and biological evaluation of dipicolylamine sulfonamide derivatized platinum complexes as potential anticancer agents

“… 18 N(SO 2 R)dpa-type tridentate ligands and their Pt( ii ) compounds with chloride leaving ligands have been synthesized and studied. 19 These N(SO 2 R)Me n dpa (R = Me, Tol; n = 2, 4) ligands are coordinated in a bidentate fashion in [PtCl 2 (N(SO 2 R)3,3′,5,5′-Me 4 dpa)] complexes, forming a rare eight-membered chelate ring. 19 The recently reported dinuclear platinum-amine compounds appeared to give rise to DNA binding at two different positions, thereby enhancing the antitumor effect.…”

“… 19 These N(SO 2 R)Me n dpa (R = Me, Tol; n = 2, 4) ligands are coordinated in a bidentate fashion in [PtCl 2 (N(SO 2 R)3,3′,5,5′-Me 4 dpa)] complexes, forming a rare eight-membered chelate ring. 19 The recently reported dinuclear platinum-amine compounds appeared to give rise to DNA binding at two different positions, thereby enhancing the antitumor effect. 20 Multinuclear platinum drugs that can contain two, three or four Pt centers with both cis and trans configurations have become an attractive strategy to develop potent cisplatin analogues.…”