We report a conceptually new polymerization technique termed migration insertion polymerization (MIP) for main chain metal-containing polymer (MCP) synthesis. Cyclopentadienyldicarbonyldiphenylphosphinopropyliron (FpP) is synthesized and polymerized via MIP, resulting in air stable poly(cyclopentadienylcarbonyldiphenylphosphinobutanoyliron) (PFpP) displaying narrow molecular weight distribution. The backbone of PFpP contains asymmetric iron units connected by both phosphine coordination and Fe-acyl bonds, which is representative of a new type of polymer. Furthermore, PFpP is tested to be soluble in a wide range of organic solvents and shown to possess reactive Fp end groups. PFpP amphiphiles have therefore been prepared via an end group migration insertion reaction in the presence of oligoethylene phosphine.

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Proteolysis targeting chimera (PROTAC) recruits an E3 ligase to a target protein to induce its ubiquitination and subsequent degradation. We reported success in the development of two PROTACs (C3 and C5) that potently and selectively induce the degradation of Mcl-1 and Bcl-2 (DC50 = 0.7 and 3.0 μM), respectively, by introducing the E3 ligase cereblon-binding ligand pomalidomide to Mcl-1/Bcl-2 dual inhibitors S1-6 and Nap-1 with micromolar-range affinity. C3-induced Mcl-1 ubiquitination translated into much more lethality in Mcl-1-dependent H23 cells than the most potent Mcl-1 occupancy-based inhibitor A-1210477 with nanomolar-range affinity. Moreover, structure–activity relationship analysis and molecular dynamic simulations discovered the structural basis for turning nonselective or promiscuous Bcl-2 family ligands into selective PROTACs. C3 and C5 exhibited reversible depletion in living cells, which provides a new potent toolkit for gain-of-function studies to probe the dynamic roles of Bcl-2 and Mcl-1 in apoptosis networks.

Cyclopentadienyldicarbonyl[(diphenylphosphino)propyl]iron (CpFe(CO) 2 (CH 2 ) 3 PPh 2 , FpP), containing both Fp and phosphine groups, was synthesized as a difunctional monomer for migration insertion polymerization (MIP). FpP underwent either intra-or intermolecular reactions in solution. When a solution with low FpP concentration (ca.1% by weight) was left at 25 °C, FpP was quantitatively converted to the fivemembered-ring species 1 via CO release. On the other hand, when a solution at the same low concentration was heated to 70 °C in the dark, an intramolecular migration insertion reaction was promoted, leading to a high conversion of FpP (ca. 70%) to the six-membered cyclic Fp acyl derivatives 2. At the same temperature with an increase in the concentration of FpP to 10% by weight, intermolecular MIR became predominant (ca. 90%) with a low yield of ring molecules (ca. 10%). Solution polymerization of FpP (ca. 20% by weight) was therefore performed at 70 °C, which generated both THF-soluble and -insoluble macromolecules via intermolecular migration insertion reactions. The resulting macromolecules were fully characterized by using FT-IR, solutionand solid-state 31 P, and 13 C NMR. The soluble macromolecules exhibit a molecular weight of ca. 4200 with a PDI value of ca. 1.24, as characterized by GPC. A kinetic study shows that the polymerization follows a step-growth mechanism.

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