Elsevier

European Polymer Journal

Volume 73, December 2015, Pages 237-246
European Polymer Journal

Chiral copoly(methacrylate)s carrying amino acid pendants in the side-chains

https://doi.org/10.1016/j.eurpolymj.2015.10.017Get rights and content

Highlights

  • Chiral poly(methacrylate)s were made from side-chain amino acid containing monomers.

  • Secondary structure conformations of the homo- and co-polymers were investigated.

  • α-Aminoisobutyric acid does not play any role to form helical poly(methacrylate)s.

Abstract

Main chain chiral poly(methacrylate)s have been synthesized by controlled reversible addition–fragmentation chain transfer (RAFT) copolymerization of chiral monomer Boc-l-alanine methacryloyloxyethyl ester (Boc-l-Ala-HEMA, A) with Boc-d-alanine methacryloyloxyethyl ester (Boc-d-Ala-HEMA, B) and achiral monomer Boc-2-methylalanine-methacryloyloxyethyl ester (Boc-Aib-HEMA, C), and B with C by changing comonomer feed compositions. We systematically examined the role of l-alanine, d-alanine and 2-aminoisobutyric acid (Aib) as folding nuclei in our designed hybrid polymer-amino acid conjugates. Specific optical rotation and circular dichroism (CD) spectroscopy studies reveal that poly(Boc-l-Ala-HEMA) and poly(Boc-d-Ala-HEMA) formed entirely opposite handed helical structure stabilized by intramolecular hydrogen bonding among the pendant chromophores of the chiral monomers. Poly(Boc-Aib-HEMA) formed random coil structures conformation (unstructured conformation), whereas the resultant copolymers of C with A and B showed an unusual linear relationship of optical activity against comonomer composition, in sharp contrast with Green’s “majority” and “sergeant-and-soldier” rule. After Boc-group expulsion in acidic environment from the polymer side-chains, backbone retained its helicity. Variable temperature chiroptical properties investigation was also performed to examine the thermal stability of the homo and copolymer’s helical conformations. Additionally, pH induced conformational transformation was observed for the homo and copolymers.

Introduction

The helix being the most common higher order structure of biomacromoleules such as nucleic acids and proteins [1], [2]; makes them novel functional materials with unique properties. Stimulated by the elegant and beautiful helical conformations in natural macromolecules, tremendous efforts are being devoted from the scientist community for designing and synthesizing artificial helical macromolecules with an aim to mimic some functions in synthetic polymers. These polymers have found applications in the field of biotechnology such as in artificial neurons in smart robotics, synthetic muscles in intelligent devices, scaffold matrices in tissue engineering and other nano-devices [3], [4], [5]. The parallel advancement of organic and polymer chemistry afforded a great number of excellent helical polymers which have the potential to be used as chiral polymeric catalyst for asymmetric organic synthesis [6], [7], [8], [9], [10], chiral stationary phases for chiral chromatographic separation of racemic compounds [11], [12], [13], nonlinear optical materials [14], [15], and some other optoelectronic and photonic substances [16], [17]. To date, different types of artificial helical polymers have been synthesized such as polyisocyanates [18], [19], polyisocyanides [20], [21], polymethacrylates [22], [23], polysilanes [24], [25], polychloral [26], which utilize steric repulsion among bulky side-chain to maintain helical conformations. Whereas poly(N-propargylamide)s [27], [28], poly(N-butynylamide)s [29], [30], poly(N-propargylcarbamate)s [31], [32], poly(N-propargylurea) [33], poly(N-propargylthiourea)s [34] adopt helical conformation stabilized through intramolecular hydrogen bonding among the pendant units of the polymer chain together with the steric repulsion between the side-chains in the biomimetically same way as peptides and proteins.

Helical polymers synthesized so far can be categorized into two different classes depending on the inversion barrier of the helical polymeric chain. The polymers which have high helix inversion barrier are called static helical polymers. Besides, dynamic helical polymers such as polyisocyanates and polyacetylenes have low inversion barrier [6], [35], [36], which have been reported to exhibit remarkable chiral amplification characteristics. Green et al. proposed “sergeants-and-soldiers” [37] rule for the copolymer systems composed of achiral monomer with minute amount of chiral monomer and give essentially the same optical activity as a chain made entirely from the chiral units. Whereas “majority” [38] rule is reserved for the copolymerization of enantiomeric monomers. This cooperative phenomenon has also been observed in some other helical polymers as well as some self-assembled suprastructures [39]. Most of the pioneering works of helical polymers especially by Yashima, Masuda, and Tang groups have been done based on main chain conjugated system with small pendant units [40], [41], [42]. Okamoto’s group have made significant contributions on chiral polymethacrylates carrying bulky aromatic side-chains [43], [44]. Recently Zhang et al. have reported methacrylate based helical dendronized polymers having side-chain dense bulky chiral amino acid substituent, which are stable at wide range of tested temperature and polarity of the solvents [45], [46], [47].

Recently, we have reported that side-chain chiral amino acid containing methacrylate monomers undergo reversible addition–fragmentation chain transfer (RAFT) polymerization to afford corresponding polymers having predominantly one-handed helical conformation. The chirality of the monomers from which the helix is being formed always determine the screw sense of the helix [48], [49], [50]. On the other hand, several groups approached to control the conformation of peptide which is composed of main-chain amino acids [51], [52]. To create such helical conformation of peptide, inclusion of α,α-disubstituted α-amino acids (dAAs) into the backbone is a powerful technique, because the dAAs can restrict the conformational freedom of their peptide and subsequently stabilize the secondary structures [53], [54]. Among different dAAs, α-aminoisobutyric acid (Aib), in which the α-hydrogen of l/d-alanine is substituted with a methyl group, has extensively been used to stabilize the helical conformation of the peptides. Aib may be viewed as the superimposition of l-and d-alanine acids. The conformational space of Aib residue is limited to right-handed and left-handed alpha helical region of the Ramachandran plot. But Aib being an achiral amino acid does not induce helical screw sense. Although Aib has shown to be playing a decisive role in helical arrangement of peptide, there are no reports on incorporation of Aib as pendant group in any kind of polymeric backbone. Therefore, the lack of knowledge relating to the inclusion of Aib exclusively in a side-chain of a polymeric backbone or with some chiral amino acid containing monomer, which has propensity to form predominantly one handed helical chain conformation, motivated us to investigate the current system. In this present study, we have synthesized homo and copolymers with varying comonomer compositions from a pair of enantiomeric monomer (Boc-l-Ala-HEMA with Boc-d-Ala-HEMA) to examine “majority rule” principle, and chiral/achiral comonomers (Boc-l-Ala-HEMA/Boc-d-Ala-HEMA with Boc-Aib-HEMA) to investigate “sergeant and soldier” principle. To the best of our knowledge there are no reports in the literature to date on chiral structure formation from the main chain chiral copoly(methacrylate) having amino acid pendant units and the dependence of their helical structures on the comonomers compositions.

Section snippets

Materials

Boc-l-alanine (Boc-l-Ala-OH, 99%), Boc-d-alanine (Boc-d-Ala-OH, 99%) and trifluoroacetic acid (TFA, 99.5%) were purchased from Sisco Research Laboratories Pvt. Ltd., India and used as received. 2-Aminoisobutyric acid/2-methyalalanine (Aib-OH, 98%), di-tert-butyl dicarbonate (Boc2O, 99%), 4-dimethylaminopyridine (DMAP, 99%), dicyclohexylcarbodiimide (DCC, 99%), 2-hydroxyethyl methacrylate (HEMA, 97%) were obtained from Sigma and used without any further purification. The

Synthesis and characterization of homo and copolymers

Our earlier studies showed that CDP is an efficient chain transfer agent for RAFT polymerization of side-chain amino acid containing methacrylate monomers [48], [50]. Therefore, we employed CDP as RAFT agent for homo and copolymerization of three different monomers to have three different sets of total 18 polymers from Boc-l-Ala-HEMA and Boc-d-Ala-HEMA with Boc-Aib-HEMA, and copolymers from the two enatiomeric monomers in DMF at 70 °C using AIBN as radical initiator (Scheme 1). The

Conclusion

Well-defined chiral/chiral and chiral/achiral copolymers were successfully synthesized from side-chain amino acid tethered methacrylate monomers by RAFT polymerization with moderate molecular weight in good yields. The insertion of l-alanine and d-alanine in the polymer backbone induces helicity having opposite handedness in the hybrid polymer-amino acid conjugates. Interestingly, Aib, which acts as folding nuclei of helical conformations in peptides, has promoted unstructured conformation in

Acknowledgements

This work was supported by Department of Science and Technology (DST), India [Project No.: SR/S1/OC-51/2010]. Kamal Bauri acknowledges Council of Scientific and Industrial Research (CSIR), India for senior research fellowship. S.K.D. acknowledges DST, India for his INSPIRE fellowship.

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