Encoding metal coordination pathways and nuclearity by molecular knotting

Precise control over the nuclearity and spatial organization of metal ions is a central objective in coordination chemistry. Knotting imposes severe geometric constraints on frameworks but has rarely been exploited to organize inequivalent metal-binding sites within a single ligand. Here we report that a molecular cinquefoil knot containing both bidentate and tridentate chelating sites enables programmed metal-ion coordination pathways. Direct metalation affords Mn(II)₅-, Fe(II)₅-, Co(II)₅-, and Cd(II)₅-knots through a dinuclear intermediate and an unusual 2-to-5 metal nuclearity progression, even though these metals do not template knot formation. Crystallization of a Mn(II)₂-intermediate reveals partial demetalation but retains a Mn(II) center displaying a "3 + 3" coordination mode, whereas all Fe(II) ions in the fully metalated Fe(II)₅-knot adopt a "3 + 2" binding geometry. Together with computational simulations, these observations support a stepwise metalation mechanism in which the dinuclear "3 + 3" coordination environment evolves into the "3 + 2" motif of the pentanuclear knot. Although the Ni(II)₅- knot cannot be obtained by direct metalation because of slow incorporation, it forms readily via transmetalation from a Zn(II)₅-knot. Circular dichroism measurements show that chiral expression is dictated by the overall ligand arrangement rather than the identity of the metal ions. The work demonstrates molecular knotting as a strategy for pathway-controlled multi-metallic assembly.