Polypeptide‐b‐Poly(Phenyl Isocyanide) Hybrid Rod‐Rod Copolymers: One‐Pot Synthesis, Self‐Assembly, and Cell Imaging

Abstract

Hybrid rod-rod diblock copolymers, poly(γ-benzyl L-glutamate)-poly(4-cyano-benzoic acid 2-isopropyl-5-methyl-cyclohexyl ester) (PBLG-PPI), with determined chirality are facilely synthesized through sequential copolymerization of γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) and phenyl isocyanide monomers bearing chiral menthyl pendants using a Ni(cod)(bpy) complex as the catalyst in one-pot. Circular dichroism and absorption spectra reveal that each block of the block copolymers possesses a stable helical conformation with controlled helicity in solution due to the induction of chiral pendants. The two diastereomeric polymers self-assemble into helical nanofibrils with opposite handedness due to the different chiral induction of the L- and D-menthyl pendants, confirmed by transmission electron microscopy (TEM). Deprotection of the benzyl groups of the PBLG segment affords biocompatible amphiphilic diblock copolymers, poly(L-glutamic acid)-poly(4-cyano-benzoic acid 2-isopropyl-5-methyl-cyclohexyl ester) (PLGA-PPI), that can self-assemble into well-defined micelles by cosolvent induced aggregation. Very interestingly, a chiral rhodamine chromophores RhB(D) can be selectively encapsulated into the chiral polymeric micelles, which is efficiently internalized into living cells when directly monitored with a confocal microscope. This contribution will be useful for developing novel rod-rod biocompatible hybrid block copolymers with a controlled helicity, and may also provide unique chiral materials for potential bio-medical applications.

Synthesis of Unimolecular Micelles with Incorporated Hyperbranched Boltorn H30 Polyester modified with Hyperbranched Helical Poly(phenyl isocyanide) Chains and their Enantioselective Crystallization Performance

“…This result directly illustrated that the H30‐PLLA‐PPI( d ) possessed optical activity helical structures. According to our early study, the strong negative CD signal at 364 nm observed for H30‐PLLA‐PPI( d ) suggested the PPI arms possessing a predominated right‐handed helical conformation. To further elucidate the observed CD effect, two control samples were specifically prepared under identical conditions, termed as H30‐PLLA‐PPI( l ) and racemic H30‐PLLA‐PPI( l / d ).…”

“…Water was deionized with a Milli‐Q SP reagent water system (Millipore) to a specific resistivity of 18.0 MΩ cm. The optically active phenyl isocyanide monomers ( l ‐PI and d ‐PI) bearing a different chiral pendant were directly used as the same batch in our previously reported work …”

“…Although various helical poly(phenyl isocyanide)s (PPIs) with different topological structures had been synthesized by us and widely used in many fields, their applications in enantioselective crystallization were rarely explored . In this contribution, we first synthesize a new type of well‐defined CPMs, denoted as H30‐PLLA‐PPI, via ring‐opening polymerization (ROP) of l ‐lactic acid (LLA) from the hydroxyl around hyperbranched H30 and subsequent Pd(II) catalyzed living polymerization of chiral pendant bearing optically active l ‐ or d ‐phenyl isocyanide (PI) monomers.…”

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy

“…The rhodamine-encoded bifunctional catalyst ClPd(PEt 3 ) 2 -RhB-OH bearing a Pd(II) active center and a hydroxyl group was synthesized from rhodamine B hydrochloride by sequential chemical modification (scheme S1a) 31, 33-35. The chemical structure of the intermediates (1-8) during the catalyst preparation were verified by 1 H NMR spectra, and the exact structure of the final ClPd(PEt 3 ) 2 -RhB-OH was confirmed by 1 H NMR, 13 C NMR, 31 P NMR, mass spectrometry (Figure S1), and FT-IR spectrometry (Figure S2).…”

“…We envision that PPI is very attractive for IR-780 micelles due to two main reasons: (1) with a distinctive π-conjugated system, PPI has an inherently stable helical conformation in aqueous solution or in solid state, which has a structural similarity to CPPs 30, 31. Therefore, introducing hydrophilic helical PPI chains in the micelle shell would facilitate intracellular delivery of cargos and create an artificial synthetic helical polymer-based delivery system.…”