To design versatile ordered nanomorphologies from the alternating sequence-controlled amphiphilic copolymers, in the current work, we have investigated the self-assembly behavior of a series of alternating copolymers, prepared through the reversible addition− fragmentation chain transfer (RAFT) polymerization of methoxy poly(ethylene glycol) (mPEG) functionalized styrene (VBP) and fatty acid attached maleimide (MF) monomers. The copolymers efficiently induced self-aggregation of the pendant side chains to afford both micelle and vesicle nanostructures in aqueous medium depending on the amphiphilicity of the side chains, as evident from dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. The copolymers also induced thermoresponsive phase transition in water with lower critical solution temperatures (LCST) in the range of 69−88 °C depending on the mPEG side chain lengths, as determined from UV−vis spectroscopy. The hydrophobic dye and hydrophilic drug loading abilities of the synthesized copolymers were investigated using nile red and doxorubicin hydrochloride (DOX•HCl) as model compounds, respectively. The copolymers further formed reverse micelles in hexane owing to the presence of hydrophobic fatty acid pendants in the side chains, for which hexane is a good solvent. Additionally, the in vitro cytotoxicity study was performed for the synthesized alternating copolymers which revealed their nontoxic nature up to 500 μg/mL polymer concentration. Thus, the current work represents a fundamental strategy to construct biocompatible polymeric nanostructures from amphiphilic alternating copolymers, endowing noteworthy features for potential advantages.

A series of copolymers with controlled monomer sequences are prepared via the reversible addition−fragmentation chain transfer polymerization of tert-butyl carbamate (Boc)-L-alanine (VBA) and Boc-L-alanyl-L-leucine-conjugated styrenic (VBD) monomers with L-alanine-appended maleimide (NMA). Monomer distribution in the copolymer is examined by both 1 H and 13 C NMR spectroscopy which eventually confirms an alternate placement of the different monomers throughout the polymer main chain in both the copolymerization systems: VBA−NMA and VBD−NMA. After the successful expulsion of the pendant Boc groups, the deprotected copolymers with free −NH 3 + and −COOH functionalities in the side chain show pHinduced solubility transition in the pH range 3−8. As signified from 1 H NMR analysis, this solubility transition is mainly associated with a pH-dependent schizophrenic core−shell alteration of the aggregated polymer structure in aqueous solution which is also supported by the dynamic light scattering measurements showing a variation of the hydrodynamic diameters of the aggregates at different solution pH values. Scanning electron microscopy and transmission electron microscopy further evidenced the schizophrenic nature of deprotected copolymers where significant morphological variations (from spherical micelles to vesicles or nearly wormlike aggregates) are obtained as a result of varying the solution pH value. The observed morphologies at different solution pH values are explained via computer simulations of a model chain with varying hydrophobicity of alternating side groups. Such schizophrenic morphological transitions of the deprotected copolymers enable us to investigate their drug encapsulation and sustained release behaviors depending on the pH of the aqueous solution. To the best of our knowledge, this is the first report where an alternating copolymer shows pH-induced schizophrenic morphological transition behavior.

A remarkable enhancement in crystalline melting temperature (Tm) was observed in a series of fatty acids and mPEG containing alternating copolymers with the lone increase in mPEG chain lengths.

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Synthesis of a sequence‐controlled polymer via reversible addition‐fragmentation chain transfer polymerization is reported herein, using an N‐substituted maleimide monomer bearing tert‐butyl carbamate (Boc)‐protected l‐alanine (M1) and Boc‐d‐alanine appended styrenic monomer (M2). The monomer sequence distribution along the polymer chain is thoroughly studied by 1H and 13C NMR spectroscopy and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry, confirming the alternating placement of l‐alanine and d‐alanine throughout the polymer chain. Copolymers display fluorescence properties in various organic solvents. After the deprotection of Boc‐groups, the copolymers show fluorescence activity in water (and also in several organic solvents), and pH‐responsiveness in aqueous medium due to the protonation/deprotonation of the side‐chain ‐NH2 groups at varying aqueous solution pH. In addition, the presence of different enantiomeric structures of alanine in the side‐chain enables us to investigate the chiroptical properties of the polymers.