Self-assembly and Temperature-driven Chirality Inversion of Cholesteryl-based Block Copolymers

Block copolymers (BCPs) comprising of a poly(methyl methacrylate) (PMMA) block and a poly(cholesteryloxyhexyl methacrylate block (PChMA) were synthesized ​ via ​ reversible addition-fragmentation chain transfer (RAFT) polymerization. The self-assembly of the liquid crystalline block copolymers was characterized by differential scanning calorimetry (DSC), polarized optical microscopy (POM) and synchrotron-based small-angle X-ray scattering (SAXS). The results indicate the formation of both tilted and non-tilted chiral smectic (SmC* and SmA*) phases. A phase transition from SmA* to SmC* phase on cooling was observed for BCPs, but not for PChMA homopolymers. The layer spacing (5.00 ± 0.18 nm) between those can be controlled to maintain the number of ChMA ​ units whilst varying the lengths of the PMMA ​ block, introducing thus systematically the SmC* phase. Furthermore, BCPs with short PMMA block showed inversion of chirality at specific temperatures; while for PChMA attached with long PMMA block no chirality inversion was observed. This mode of chirality switching, investigated by CD, NMR, and theoretical studies, is associated with the methyl substituents in the backbone affecting the packing of the polymers. The basic rules, described here, have the potential to be implemented for the design of a wide range of functional materials where helix-helix conversion is of use. we demonstrate another mechanism for controlled chirality switching without any additional chiral dopants exists, which to the best of our knowledge, has not been reported yet. It is based on the temperature controlled packing frustration of suitably selected block copolymers consisting of side-chain liquid crystal and aliphatic blocks of carefully defined dimensions. Our results are shown for a specific set of materials, however, as the driving for the chirality inversions are related to the rearrangement of what are essentially hydrocarbon blocks; we anticipate that the approach can be extended to other materials. To show the general versatility of the concept we utilized an optimized system, consisting of the ubiquitously employed cholesteryl group as a chiral and mesogenic unit separated from a methacrylate main chain by a hexyl spacer. For the other block, a simple coil poly(methylmethacrylate) chain was selected. We note here that the investigated system does not contain aromatic groups and is hence transparent at wavelengths above ~ 320 nm allowing thus for the future inclusion of further functionality.


INTRODUCTION
The research on polymers with liquid crystalline (LC) pendants has emerged as one of the major topics in materials science. [1][2][3][4][5][6][7][8] The combination of BCP topology and LCs is expected to allow for the design of advanced features in functional materials, allowing thus miniaturization of domain spacing in nanoscopic materials, high processability and the designing of novel morphologies. [9][10][11][12] In addition, the introduction of chiral functionality to LCPs has become one of the most important topics in LC research as it may permit the introduction of chiral nanostructures due to chiral amplification. The combination of LC polymers with chiral mesogens may result in chiral soft materials with superior properties and applications as, e.g. electronic and photonic materials.
LC block copolymers (BCPs) are the combination of LC mesogens with non-liquid crystalline and incompatible blocks. One of the most reported LC-BCPs is rod-coil BCPs 13,14 and this architecture permits the systematic shrinking in volumes. More specifically, rod-coil BCPs containing LC groups can combine the rigidity of the mesogenic part with the higher flexibility of the soft block and improve the chain stretching. For well-defined systems a corona-like shell around the LC block can generate nanophase separation of LC blocks resulting in complex phase behaviour and extremely small domain volumes. Interestingly LC-BCPs can act as a unique candidate for the analysis of the impact of an additional level functionality in the rigid core on the organization of well-defined macromolecular assemblies. In addition, internal LC ordering can be tuned from a less-ordered nematic or cholesteric phase to high-ordered smectic phase by changing the synthetic strategy of LC blocks or other coinciding parameters. 15,16 Chirality switching has been observed in the case of optically active small molecules and polymers by a range of external stimuli, such as temperature, photoisomerization, pH, the addition of chiral dopants and solvent polarity. [17][18][19][20] Temperature as a stimulus for chirality switching is very attractive as the temperature can typically be measured and controlled with high precision and the response is usually fast. Moreover, it removes the requirement for increasing the complexity of the investigated system by the incorporation of trigger or switching moieties; hence this approach has been termed additive free. 21,22 Fujiki et al 23,24 reported an optically active helical polysilylene comprising a rod-like main chain, undergoing a thermo-driven chirality inversion in dilute isooctane solution. In addition, Tang et al 25 reported helical-switching polymers such as poly( n -hexyl isocyanate) used as chiral dopants in lyotropic liquid crystals and observed the helical-twist phenomenon as a function of temperature.
Here we demonstrate another mechanism for controlled chirality switching without any additional chiral dopants exists, which to the best of our knowledge, has not been reported yet. It is based on the temperature controlled packing frustration of suitably selected block copolymers consisting of side-chain liquid crystal and aliphatic blocks of carefully defined dimensions. Our results are shown for a specific set of materials, however, as the driving for the chirality inversions are related to the rearrangement of what are essentially hydrocarbon blocks; we anticipate that the approach can be extended to other materials. To show the general versatility of the concept we utilized an optimized system, consisting of the ubiquitously employed cholesteryl group as a chiral and mesogenic unit separated from a methacrylate main chain by a hexyl spacer. For the other block, a simple coil poly(methylmethacrylate) chain was selected. We note here that the investigated system does not contain aromatic groups and is hence transparent at wavelengths above ~ 320 nm allowing thus for the future inclusion of further functionality.
Specifically, we report here the synthesis of a series of LC-BCPs by reversible addition-fragmentation chain transfer (RAFT) polymerization; the full chemical characterization of the polymer properties, including the tacticity of the main chain by detailed NMR studies, as well as the characterization of the LC properties by temperature dependent polarizing optical microscopy (POM), differential scanning calorimetry (DSC) and synchrotron-based small-angle X-ray scattering (SAXS) studies. The chirality and temperature dependent chirality inversion were measured by circular dichroism (CD) measurements of thin films whose thicknesses were determined by profilometry. The analysis of the results was underpinned by detailed simulation studies relating spectroscopic data to molecular conformation; the molecular conformations and their assemblies are responsible for the changes of chirality inversion. The polymerization reaction was carried out by reversible addition-fragmentation chain transfer (RAFT) polymerization of 4-cyanopentanoic acid dithiobenzoate (CPADB), enantiomerically pure cholesteryl methacrylate (ChMA) as well as methylmethacrylate (MMA) as monomers using azobisisobutyronitrile (AIBN) as an initiator and toluene as a solvent. The PChMA macroinitiators bearing cholesterol moieties were first obtained from the RAFT polymerization of enantiomerically pure ChMA monomer using the RAFT agent (CPADB) and then utilized in the preparation of LC-BCPs (PChMA -b -PMMA) with various DPs ( N ).

Synthesis of cholesteryloxyhexyl methacrylate (ChMA)
Cholesteryloxyhexanol (Ch-OH) (0.5 g, 1.0 mmol) in dichloromethane (20 ml), methacryloyl chloride (0.15 ml, 1.5 mmol) and triethyl amine (0.42 ml, 3.1 mmol) were stirred at room temperature for 6 h. Upon completion, the reaction mixture was extracted with dichloromethane, washed with brine and concentrated by rota-evaporation. The crude mixture was then purified by silica gel column chromatography using petroleum ether:ethylacetate (9:1) solvent mixture, A typical procedure for the synthesis of PChMA-b -PMMA is as following: PChMA 12 (0.50 g, 71.9 µmol), methyl methacrylate (0.28 g, 2.8 mmol), AIBN (2.20 mg, 14.1 µmol) and toluene (0.5 ml) were placed in a Schlenk tube. The mixture was degassed by three freeze-pump-thaw cycles and sealed under nitrogen. The reaction tube was placed in an oil bath at 70°C for 6 h and the reaction was quenched by dipping the tube in ice. The mixture was precipitated in hexane and dried under reduced pressure. The polymer product was a colorless solid. We note that different temperatures were applied for the polymerization of the two monomers, i.e. ChMA and MMA are polymerized at respectively, 80°C and 70°C. Such differences in the reaction temperatures are needed as suggested by test reactions. For ChMA homopolymers, we observed that when setting the reaction temperature at 70°C in initial trials, the polymerization rates were very low, yielding broad molecular weight distributions of the resulted polymers. Such slow reactions may be due to the steric hindrance of the bulky cholesteric units. Hence, a high temperature was applied for ChMA polymerization to allow faster reactions. In contrast, MMA polymerizations were performed at 70°C, which is a typical temperature for methacrylate polymerization mediated by the RAFT mechanism with AIBN as initiator. Indeed polymerizations at 80°C were also explored initially and we detected that the reactions rates were to too fast resulting in poor control of the polymer structure. Hence, the reaction temperature for the preparation of homo and block copolymers were set at 80°C and 70 °C, respectively.  Table 1. Higher values of M n from SEC were obtained than those calculated from NMR data. This can be ascribed to the relatively large coil size of PChMA-b -PMMA in THF when compared to the PMMA calibrator with the same molecular weight. 29 In addition, the Ð values of the copolymers were also obtained, with most of the values lower than 1.35 indicating an acceptably good control of the polymerization via RAFT mechanism. We note that the slightly higher Ð values than observed for typical RAFT polymers are however reasonable for the polymerization of bulky monomers, such as ChMA used for LC-BCP and in line with results obtained for other liquid crystal side-chains. 49 We attribute this to the steric hindrance of monomer units at the ω-end of the "living" polymer chains which may hinder the chain transfer efficiency of CTA. Such hindrance may occur in the RAFT polymerization of both ChMA and MMA at early stage.  Microstructure analysis and steric effects of the LC-BCPs were further evidenced by 1D

Synthesis of cholesterol based LC polymers
and 2D NMR analysis. Carbonyl carbon resonance peak assignments of PChMA and PChMA-b -PMMA were clearly identified by NMR analysis (Figures 1 and S4  deduced that PChMA blocks exist predominantly as syndiotactic species, which may be ascribed to the strong steric hindrance between the bulky LC mesogens. With the addition of an PMMA block, which is relatively soft and heterotactic, the overall syndiotactic species decreases with the increasing of the DP of MMA, as shown in Table S1). In addition to that, in the case of  The LC properties of all the synthesized cholesterol-based homo-(macro-CTA) and block copolymers were fully evaluated by differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) (For experimental details, see SI). All compounds form thermostable (enantiotropic) liquid crystalline phases from room temperature to the clearing points ( Figure   S9). The clearing-point enthalpies for the homo and BCPs emerge are somewhat broad due to a biphasic region which is a result of the dispersity ( Ð ) of the polymers and the presence of a non LC isotropic block. 19 The phase transition temperatures and their corresponding enthalpies of all the homo-and block copolymers are summarized in Table 1

Circular Dichroism of the cholesterol derived LC-homo and BCPs
To measure and investigate the differences between BCPs with short and long PMMA blocks we performed precise thin-film CD analysis for LC-BCPs. For measurements, all in the SmA phase, polymeric thin films were prepared so that homeotropic orientation was achieved; the

Electronic properties and Conformational analysis
The electronic transition properties of the LC-BCPs were evaluated experimentally and theoretically, in order to understand the nature of electronic transitions present in the polymers.
Simulations of the UV-vis and CD spectra were carried out on the TD-DFT/B3LYP/6-31+G(d,p) basis level. The simulated and experimental electronic transition spectra of LC-BCPs are observed at 267 nm and 264 nm, which is closely matched with experimental value as shown in Table S2. For LC-BCPs, the electron density distribution of the highest occupied molecular orbitals (HOMO) over cholesterol moiety, while in contrast the lowest unoccupied molecular orbitals (LUMO) located in the dithiobenzoate region of the LC-BCP, which indicates that the intramolecular charge (ICT) process 45,46 from the electron donor HOMO to electron acceptor (LUMO) group ( Figure S27).
The conformational analysis of the LC-BCPs was carried out to identify their ground-state geometry through Density functional theory (DFT) calculation. 47 The potential energy surface (PES) scan was performed as a function of PMMA-thiol linkage dihedral angle (C 2 -S 21 -C 15 -C 20 ) with a fixed cholesteryl unit by varying the dihedral angles for every 10 degrees of rotation at B3LYP/6-31G(d,p) basis set level. The LC-BCP possesses two equally possible conformers such as syn -and anti -forms with different energy levels as shown in Figure 6 ( Figure   S28). From the PES curve, the highest energy domain of syn -form is located at 116°(-3309.2861 Hartree) and the lower energy of anti-form is located at 66°(-3309.29106 Hartree). In comparison, the anti-form possesses global minima, which exhibits a more stable conformer than syn -form. 48 In addition, the energy barrier between the syn -and anti -forms is 13 kJ/mol. This

CONCLUSIONS
In summary, we explored the mesophase mediated self-assembly structures of well-defined block copolymers with a methacrylate main chain. The block size was systematically varied; consisting of two incompatible blocks; one a cholesteryl unit as a rigid block and the other a methyl group as a soft block. The polymers were prepared by RAFT polymerization and the block sizes of the block copolymers were varied systematically in size and measured by GPC and the regiochemistry of the backbone was identified by detailed NMR studies identifying pentads of the repeat units. Mesophase formation is controlled by the size of the polymers and the block composition. For block copolymers (PChMA-b -PMMA) consisting of large PMMA blocks the phase sequence SmA*-SmC* was detected, based on DSC, POM, and synchrotron SAXS studies; while for polymers containing short PMMA blocks, no SmC* phase was formed, instead chirality inversion occurs as measured by temperature dependent CD spectroscopy in thin films and supported by DFT simulations. Notable is the absence of signals for superstructures based on microsegregation of chemically different blocks, a typical means for block co-polymers to minimize energy .
We identify the chirality inversion in the short block polymers as the predominantly syndiotactic tacticity of the PChMA blocks, which prevent efficient packing for those with low ratio of PMMA block at low temperatures -such as the formation of SmC* structures of the cholesteryl units. The polymers escape the energy penalty at low temperatures by finding low energy conformations associated with a chirality inversion in the CD signals associated with the cholesteryl groups; whilst SAXS and POM data indicate that an overall lamellar ordering is maintained. The effect measured here may be present at some of the temperature-driven helix-helix transitions in nature and has the potential to be exploited further for artificial systems.

Supporting Information
Experimental methods, NMR, DSC, POM, SAXS, WAXS, CD and theoretical calculation results are included in the supporting information.

Notes
The authors declare no competing financial interest.