**Determination of Optical Purity of Lactic Acid-Based Chiral Liquid Crystals and Corresponding Building Blocks by Chiral High-Performance Liquid Chromatography and Supercritical Fluid Chromatography**

**Anna Poryvai <sup>1</sup> , Terezia Vojtylová-Jurkoviˇcová 2, Michal Šmahel 1, Natalie Kolderová 1,3, Petra Tomášková 2, David Sýkora <sup>4</sup> and Michal Kohout 1,\***


Received: 30 January 2019; Accepted: 14 March 2019; Published: 20 March 2019

**Abstract:** Liquid crystals (LCs) are among the most prominent materials of the current information age, mainly due to their well-known application in liquid crystal displays (LCDs). Their unique electro-optical properties stem from their ability to form organised structures (mesophases) on the transition from solid state to isotropic liquid. Molecules of LCs in a mesophase still maintain the anisotropy of solid crystals, while simultaneously exhibiting the fluidity of liquids, which gives the system the ability to react immediately to external stimuli such as electric or magnetic fields, light, mechanical stress, pressure and, of course, temperature. For the proper function of LC-based devices, not only chemical, but also optical purity of materials is strongly desirable, since any impurity could be detrimental to the self-assembly of the molecules. Therefore, in this study we aimed to verify synthetic methods published in the literature, which are used nowadays to prepare chiral building blocks based on lactic acid, for their enantioselectivity. Moreover, we have focused on the development of an analytical chiral separation method for target liquid crystalline materials. Using a chiral polysaccharide-based column operated in liquid chromatography mode, we show that not all published methods of LC synthesis are enantioselective, which could lead to significant differences in the properties of the resulting materials. We show that high-performance liquid chromatography with UV detection and supercritical fluid chromatography with UV and mass spectrometry detection enable full control over the chemical and optical purity of the target LCs and the corresponding chiral building blocks. For the first time, we utilise supercritical fluid chromatography with mass detection for the direct chiral analysis of liquid crystalline materials and impurities formed during the synthesis.

**Keywords:** chiral liquid crystals; optical purity; chiral separation; supercritical fluid chromatography; enantioseparation of liquid crystals; mass spectrometry detection; mesomorphic properties

#### **1. Introduction**

Liquid crystals (LCs) represent one of the most prominent classes of materials of today's information age. The molecules of LCs can self-assemble into organised supramolecular structures (mesophases) that combine the fluidity of liquids with the long-range order of solids [1,2]. Molecules in a mesophase readily respond to external stimuli such as electric and magnetic field, light and mechanical stress. Thanks to these properties, LCs have found many applications, for example, in liquid crystal displays (LCDs), optical shutters, light beam steering and shaping [3,4].

Among LCs, chiral liquid crystals (CLCs) represent an important class of materials that can self-assemble into chiral mesophases [5]. Macroscopic chirality of the mesophases results in special properties, such as (anti)ferroelectricity, selective reflection of light, and heat sensitivity, which render CLCs ideal candidates for the fabrication of high-speed high-contrast LCDs, photonic devices, and contact thermography devices, respectively [1,6,7]. Since the self-assembly of LCs is very sensitive to any impurities present in the bulk material, control of chemical and optical purity during the synthesis of target CLCs is essential. Any impurity may result in the alteration of the mesophase structure or even complete loss of mesomorphic behaviour.

The optical purity of CLCs was in the past mainly controlled by optical rotation measurement and transformation of precursors to diastereoisomers [8]. However, such transformation does not usually provide information on trace amounts of other stereoisomers, which can be present in the final material. Even a trace of the opposite enantiomer may consequently lead to variations in the mesomorphic behaviour expected for the enantiomerically pure material. The source of such optical impurity may be the starting material, which frequently contains a trace amount of the opposite enantiomer, or it may occur during synthesis due to partial racemisation of an intermediate upon its synthetic modification. Although the optical purity of CLCs is a very important issue in the development and utilisation of novel chiral materials, only scarce information on chiral separation of CLCs can be found in the literature [9,10]. Most of the work thus far has been devoted to chiral liquid chromatography separation of photosensitive CLCs and the effect of light-induced *E*-to-*Z*-isomerisation on chiral recognition [11–13]. It has been found that the structure of CLCs plays an important role in the chiral resolution. It has also been documented that even materials bearing very small substituents at the chiral centre can be efficiently separated on polysaccharide-based chiral columns [9,10]. However, to the best of our knowledge, there is no systematic study dealing with the control of enantioselectivity of the synthetic protocol leading to CLCs using contemporary analytical chemistry instrumentation.

Therefore, we have focused on controlling enantioselectivity of the synthesis of a novel type of lactic acid-based CLCs. We used three different synthetic procedures reported in the literature, which have frequently been used for the preparation of the chiral intermediates required for the synthesis of target lactic acid-based CLCs. We developed a method for the chiral resolution of both enantiomers of the chiral precursors using the synthesised enantiomers and verified the enantioselectivity of the synthetic pathways. Moreover, we elaborated a method for the analytical enantioseparation of the target liquid crystalline materials, not only in HPLC, but also in supercritical fluid chromatography (SFC) with mass spectrometry (MS) detection. We document that the small percentage of the opposite enantiomer present in commercially available chiral starting materials increases during the synthesis, thereby affording materials that are not optically pure. The described chiral separation procedure enables very precise control of the chemical and optical purity of the target CLCs, which is required for practical applications.

#### **2. Results and Discussion**

#### *2.1. Synthesis of Chiral Building Blocks*

The studied chiral intermediates (Figure 1) were prepared using previously described synthetic procedures and characterised by nuclear magnetic resonance techniques to comply with the data published in the literature [8,14–18]. To clarify the differences among the three methods used here, the experimental procedures are described below in brief. The method (B) is a modified version of a synthetic procedure already described in the literature [17].

**Figure 1.** Synthesis and designation of the chiral precursors prepared by three different methods; (**A**) four step method using oxidation of an aldehyde as an intermediate step, (**B**) and (**C**) direct acylation of 4-hydroxybenzoic acid with the chiral acid under different conditions.

The first two steps [8,15,16] of the synthesis are common to all three procedures, and they were accomplished as follows: A suspension of silver(I) oxide, alkyl iodide and ethyl (*S*)-lactate (or methyl (*R*)-lactate) in diethyl ether was stirred for 90 h in the absence of UV light. Then, the reaction mixture was filtered, solvent was evaporated and the product (colourless liquid) was purified via distillation under reduced pressure (*p* = 0.6 Torr, t = 54–55 ◦C for *S*-C6; *p* = 2.4 Torr, t = 143–146 ◦C for *S*-C12). Subsequently, an aqueous solution of lithium hydroxide (1.3 M) was added dropwise to a stirred solution of ethyl *O*-alkyllactate in methanol (with THF in the case of dodecyl derivative) at 0 ◦C. The reaction mixture was stirred for 3 days at room temperature, then it was acidified (pH = 2) with 17% aq. hydrochloric acid and extracted with dichloromethane (3 × 20 mL). The combined organic solution was dried with anhydrous magnesium sulphate. Solvent was removed under reduced pressure and the corresponding *O*-alkyllactic acid was isolated as a colourless liquid. For analytical data of the derivatives, see ESI.

#### 2.1.1. Method (A)

To the solution of **1a** in dry DCM, *p*-hydroxybenzaldehyde, *N*,*N*'-dicyclohexylcarbodiimide (DCC) and 4-*N*,*N*-dimethylaminopyridine (DMAP) were added, and the reaction mixture was stirred in an inert argon atmosphere overnight, and then it was decomposed with 17% aq. hydrochloric acid [14,18]. Layers were separated, and the aqueous layer was extracted with ethyl acetate (2 × 20 mL). The combined organic solution was washed with brine (10 mL) and dried with anhydrous magnesium sulphate. The solvent was removed, and the crude white product was purified by column chromatography (eluent toluene/*tert*-butyl methyl ether, 30/1, *v*/*v*). To a cold (0 ◦C) solution of aldehyde in acetone, Jones reagent was added dropwise under stirring. The reaction mixture was left to heat up to room temperature and stirred overnight. Then, the reaction mixture was poured onto crushed ice (400 mL). After all the ice had melted, the formed precipitate was filtered, washed with cold water and dried in air. The crude product was purified via crystallisation from hexane.

#### 2.1.2. Method (B)

A mixture of acid **1a** with a catalytic amount of *N*,*N*-dimethylformamide (DMF) (0.05 mL) in oxalyl chloride (10–20 mL) was stirred at room temperature overnight. The unreacted oxalyl chloride was distilled off, and the residue was boiled for 1 min in hexane with a spatula-tip of active carbon. The suspension was filtered while hot and the solvent was evaporated. The crude acid chloride was dissolved in dry DCM (3 mL) and added dropwise to a cold (0 ◦C) solution of 4-hydroxybenzoic acid and DMAP in dry dichloromethane. The mixture was stirred at 0 ◦C in the argon atmosphere for 10 h. The reaction was then decomposed with 17% aq. hydrochloric acid. Layers were separated, and the aqueous layer was extracted with chloroform (2 × 20 mL). The combined organic solution was washed with brine (10 mL) and dried with anhydrous magnesium sulphate. The solvent was removed, and the crude white product was purified by column chromatography.

#### 2.1.3. Method (C)

A mixture of acid **1a** with a catalytic amount of DMF (0.05 mL) in oxalyl chloride (10–20 mL) was stirred under reflux for 2 h [17]. Unreacted oxalyl chloride was distilled off, and the crude product was boiled for 1 min in hexane with a spatula-tip of active carbon. The suspension was filtered while hot and the solvent was evaporated. The crude acid chloride was dissolved in dry dichloromethane (3 mL) and added dropwise to a solution of 4-hydroxybenzoic acid and DMAP in dry DCM. The mixture was stirred and heated under reflux in the argon atmosphere for 5 h. Then, it was cooled to the ambient temperature and decomposed with 17% aq. hydrochloric acid. Layers were separated, and the aqueous layer was extracted with chloroform (2 × 20 mL). The combined organic solution was washed with brine (10 mL) and dried with anhydrous magnesium sulphate. The solvent was removed, and the crude white product was purified by column chromatography.

#### *2.2. Synthesis of the Target Liquid Crystal*

The synthesis of the target liquid crystalline material (Figure 2) started from chiral acids **2a** and **2c** prepared according to methods (A) and (B), respectively, which provided the best results. The acids were first transformed to appropriate acid chlorides, which were subsequently used for the acylation of hydroxy ester **3**, prepared according to a method described in the literature [19], in the presence of DMAP as a base.

**Figure 2.** Synthesis of target LCs.

#### *2.3. Chiral HPLC Separation of Chiral Building Blocks*

The chiral separation method was based on a previously optimised methodology available in our laboratory for the enantioseparation of chiral photosensitive LCs [11–13]. Optimal separation conditions for precursors **2a**–**d** were heptane/propan-2-ol (9/1, *v*/*v*). Pure (*R*)- and (*S*)-enantiomers were screened individually, and the position of the enantiomeric impurity in the main substance was determined by comparing the retention times (Figure 3).

**Figure 3.** Enantioseparation of chiral acids **2a** and **2c** prepared according to experimental methods A–C in HPLC mode using ECOM HPLC system.

Under the given conditions, baseline resolution of the enantiomers was feasible. In addition to that, it was possible to study the effect of the particular synthetic strategy on enantiomeric purity of the chiral building blocks. The results (Table 1) show that synthetic method A provided the chiral building block **2a** with *ee* = 93.7%. The chemical purity of the substance was high. Synthetic method B, which was first used for the preparation of **2c**, gave rise to a product with higher optical purity (*ee* = 96.8%) than method A. However, several other chemical impurities were detected. An attempt to improve the reaction rate by heating up the reaction mixture (method C [17]) provided the target acid **2a** containing a broad range of chemical impurities, as well as the opposite enantiomer **2c**, resulting in *ee* = 81.6%. Similar results were obtained for acids **2b** and **2d**, possessing the C12 terminal alkyl chain (see Figure S1). Therefore, it is clear that method C should not be used for the synthesis of chiral building blocks **2a**–**d** or compounds possessing a similar structure with lactic acid as the chiral unit.


**Table 1.** Relative peak areas of chiral building blocks **2a** and **2c** obtained from chiral HPLC analysis and corresponding enantiomeric excess values of the respective enantiomers.

Since the optical purity of starting esters, as stated by the manufacturer, is *ee* = 98% for (*S*)-ethyl lactate and *ee* = 99% for (*R*)-methyl lactate, partial racemisation also occurred when using the synthetic methods A and B. First, we decided to modify method A, because it is well known that DCC (and other carbodiimides) may induce partial or full racemisation of a chiral acid during its activation [20,21]. Therefore, O-(1H-6-chlorobenzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TCTU), a more selective coupling reagent, was employed for the synthesis of **2a** using a method described for analogous reagents [22]. However, an almost identical enantiomeric composition of **2a** as for DCC-mediated reaction was achieved (see Figure S2).

The results indicate that the partial racemisation observed for building blocks prepared according to methods A and B most probably takes place during the first two steps of the synthesis, although the methodology was previously described as racemisation-free [8,23]. Therefore, it is reasonable to assume that with the development of new analytical approaches, the precision of impurity determination has been significantly improved. The current technology of chiral CSPs obviously beats the former methods based on optical rotation measurements and determination of enantiomeric excess by transformation of the respective chiral building blocks to an amide [8].

#### *2.4. Chiral HPLC Separation of Full-Length Liquid-Crystalline Materials*

The developed separation method for the precursors was further successfully applied for the chiral separation of full-length liquid crystals (RS = 2.5). Due to the shift in the absorption maximum of the target compound, the detection wavelength was set to 308 nm. To determine contamination of target CLCs with an opposite enantiomer, we prepared corresponding (*S*)- and (*R*)-enantiomers (**I** and **II**, respectively), and analysed them independently (Figure 4).

Analogously to the chiral precursors, (*R*)-enantiomer **II** eluted first. This documents that the enantiorecognition of the enantiomers is strictly governed by the substituents near the chiral centre, while the rest of the molecule only contributes to retention. Interestingly, the analysis of (*S*)-enantiomer **I** revealed *ee* = 98.8% and for target material **II** ((*R*)-enantiomer) *ee* = 98.4% was found. This finding contradicts the results obtained for the chiral precursors, which showed higher optical purity of the (*R*)-enantiomer. We can speculate that the target CLCs could be enantiomerically enriched via crystallisation, leading, in consequence, to target materials with higher optical purity than the starting compounds. However, intensive purification will be used, because the initial application of column chromatography and three consecutive crystallisation still provided a rather impure material (Figure 4).

**Figure 4.** Chiral separation of target chiral liquid crystals. Overlaid chromatograms of **I** (red trace) and **II** (blue trace) acquired with Chiralpak AD-3 using Acquity UPC2 operated in HPLC mode; mobile phase heptane/IPA (9/1, *v*/*v*), flow rate 1 mL/min, temperature 25 ◦C, sample concentration 0.5 mg/mL, injection volume 5 μL.

#### *2.5. Chiral SFC and SFC-MS Separation of Full-Length Liquid-Crystalline Materials*

Recently, it has been shown that SFC offers striking selectivity in the enantioseparation of chiral liquid crystals [9,10]. Therefore, we prepared a spiked sample, which enabled us to determine the elution order of enantiomers and match the chiral impurities (observed in HPLC mode) to the corresponding materials. Indeed, the SFC analysis provided better resolution (RS = 3.1), not only for the target materials, but also for chiral impurities present in the materials (Figure 5). The elution order of **I** and **II** remained unchanged; material **II** eluted in the first peak.

**Figure 5.** Mixture of **I** and **II** analysed in SFC mode on Chiralpak AD-3 to directly compare the performance of the column in HPLC and SFC mode. Mobile phase scCO2/IPA (70/30), sample concentration 0.5 mg/mL, injection volume 5 μL, temperature 30 ◦C, backpressure 2000 psi and the flow rate of 1 mL/min were used.

It should be noted that the SFC separation was, in fact, performed outside the supercritical region of the fluid [24,25]. Yet, the term SFC is generally also accepted for the subcritical fluid region (also subFC), because the main advantages of lower viscosity and higher diffusivity of the mobile phase are fully preserved [26]. Unlike normal phase HPLC, direct coupling to a mass spectrometer (detector) is easily accessible in SFC. Therefore, we took this advantage to control the optical purity of the materials and also to shed light on their impurity profile. Due to specific SFC conditions, a dedicated SFC column (ChiralArt Amylose-C 250 × 4.6 mm, i.d., 5 μm) was used in all following SFC measurements. It should be noted that a dedicated SFC column should be used for each chromatographic mode, because a frequent change of chromatographic modes could reduce column

lifetime. Although it is natural to use short columns with small particles in SFC (due to low viscosity and higher diffusivity of the fluid), in some cases it is economic to use older type of columns for SFC method development, in particular, when unusual conditions (e.g., outside supercritical region, highly acidic mobile phase) are expected to be used.

Analysis of the target material **I** (Figure 6) clearly demonstrates that the additional purification with gradient elution column chromatography and subsequent multiple crystallisations provide the chemically and enantiomerically pure material. No signals of impurities have been detected, vide infra. Furthermore, only a negligibly increased baseline was observed in the area where the peak of (*R*)-enantiomer (material **II**) should be present. Since the limit of quantification for SFC-MS is below 1 μg/mL (for details see ESI), the enantiomeric purity of the target material **I** analysed under the given conditions (Figure 6) is *ee* > 99.6%.

**Figure 6.** Analysis of purified target material **I** performed in SFC-MS mode. Upper part shows the UV trace, lower part shows reconstructed chromatograms (XIC) with the mass of the target material 539.4 [M + H]+, 561.5 [M + Na]+, fragments 263.1 [M + H]+, 383.0 [M + H]+, and the main impurity 419.0 [M + H]+ and mass spectrum of the product. Conditions: ChiralArt Amylose-C (250 <sup>×</sup> 4.6 mm, i.d., 5 μm) column, mobile phase scCO2/IPA (70/30), flow rate of 1 mL/min, sample concentration 0.5 mg/mL, injection volume 5 μL, temperature 30 ◦C, backpressure 2000 psi, ESI+.

For the analysis of impurities, impurity fractions of material **I** obtained from the column chromatography and mother liquor after re-crystallisation were collected and used. Since the mobile phase composed of scCO2 and IPA (low molar mass alcohols in general) is acidic [27,28], ESI+ was the preferred mode also for the impurities analysis. Apart from the target material **I** and the enantiomeric impurity (material **II**), several other substances were identified (Figure 7). The SFC-MS analysis shows that molecular masses of impurities correspond to fragments observed for ionised target materials. This documents that all impurities present in the target material originate from the starting compounds and side reactions among them—mainly migration of *O*-alkyllactic acid from the target materials to phenol **3** (for more detailed analysis and structures of the impurities see ESI in the Supplementary Materials).

**Figure 7.** SFC-MS analysis of major impurities (IM) of the target compound **I**. Upper part shows the UV trace, lower part reconstructed chromatograms with masses of the target materials and impurities originating from the synthesis. Conditions: ChiralArt Amylose-C (250 × 4.6 mm, i.d., 5 μm) column, mobile phase scCO2/IPA (70/30), flow rate of 1 mL/min, sample concentration 1.0 mg/mL, injection volume 10 μL, temperature 30 ◦C, backpressure 2000 psi, ESI+.

#### **3. Materials and Methods**

#### *3.1. Chemicals*

Heptane, dichloromethane (DCM), methanol (MeOH), and propan-2-ol (IPA) were purchased from LachNer s.r.o. (Neratovice, Czech Republic); all solvents were of HPLC grade. Carbon dioxide (SFC grade) was obtained from Linde Industrial Gasses (Prague, Czech Republic). Chemicals used for the synthesis of the chiral precursors and target LCs were commercial products from Sigma-Aldrich (Prague, Czech Republic), Fischer Scientific (Pardubice, Czech Republic) and they were used without further purification. Silica gel (Kieselgel 60) for the purification of the intermediates and target LCs was purchased from Merck (Darmstadt, Germany).

#### *3.2. Instrumentation and Methods*

The optical purity of chiral precursors was determined by HPLC using Chiralpak® AD-3 (150 × 4.6 mm ID, 3 μm) from Chiral Technologies Europe (Illkirch, France) column in a heptane/IPA (9/1) mixture, the flow rate was set to 1 mL/min, temperature 25 ◦C. Sample concentration was 0.2 mg/mL, injection volume 20 μL and detection wavelength was set to 235 nm. Optical purity of final liquid crystalline materials was verified under the same conditions, except for the detection wavelength, which was set to 305 nm. The ECOM HPLC system consisted of Alpha pump (ECOM, Prague, Czech Republic), CT050 controller (AZ Chrom, Bratislava, Slovakia) and ECDA2000 (ECOM, Prague, Czech Republic) detector. A part of HPLC measurements on Chiralpak AD-3 was carried out on an SFC system (operated in the HPLC mode), as specified below.

SFC measurements were performed on a SFC-dedicated column, namely ChiralArt Amylose-C (250 × 4.6 mm ID, 5 μm) from YMC Europe GmbH (Dinslaken, Germany) using an Acquity Ultra-Performance Convergence Chromatography (UPC2) system equipped with a binary solvent manager, sample manager, convergence manager, column manager 30S for eight 250 mm columns and PDA detector and single quadrupole mass detector (QDa) from Waters (Milford, CT, USA). The mobile phase consisted of supercritical carbon dioxide (scCO2) with 30% of IPA. The flow rate was set to 1 mL/min, injection volume to 5 μL. For all measurements, the backpressure was set to 2000 psi (138 bar) and the column temperature to 30 ◦C. The sample concentration was 0.5 mg/mL in a mixture of heptane/IPA (9/1, *v*/*v*). The void volume (*t*0) was determined from the first negative peak observed

after the injection. An equilibration window of 15 min was applied prior the first sample injection for each column. The PDA acquisition range was 210–400 nm and the detection wavelength was 308 nm. The mass detection was performed in positive ion mode (ESI+) with a mass range 200.00–600.00 Da, cone voltage 10 V. The ESI spray voltage was set to 0.8 kV. Empower 3 software was used for system control and data acquisition.

Nuclear magnetic resonance (NMR) spectra were acquired using an Agilent 400-MR DDR2 spectrometer (Santa Clara, CA, USA) operating at 400.13 MHz for 1H and 100.62 MHz for 13C cores. Elemental analysis was performed on a Perkin-Elmer 2400 Instrument (Waltham, MA, USA).

#### *3.3. Experimental*

#### (*S*)-Propyl 5-{4-(4-(2-hexyloxypropanoyloxy)benzoyloxy)phenyl}thiophene-2-carboxylate (**I**)

A mixture of acid **2a** (500 mg, 1.71 mmol) with a catalytic amount of DMF (0.05 mL) in oxalyl chloride (20 mL) was stirred at reflux for 2 h. The excess of the oxalyl chloride was distilled off and the residue was heated under reflux in hexane with a spatula-tip of active carbon for 1 min. The suspension was filtered, and the solvent evaporated; the crude acid chloride was dissolved in dry dichloromethane and added dropwise to a solution of hydroxyl ester **3** (374 mg, 1.43 mmol) with DMAP (174 mg, 1.43 mmol) in dry dichloromethane (25 mL). The reaction mixture was stirred in argon atmosphere at room temperature for 2 h. Then, the reaction mixture was decomposed with 17% aq. hydrochloric acid, layers were separated, and the aqueous layer was extracted with toluene. The combined organic solution was washed with brine and dried with anhydrous magnesium sulphate. The solvent was removed, and the crude product was purified by column chromatography (toluene/*tert*-butyl methyl ether 20:1, *v*/*v*) and multiple crystallisations from an ethyl acetate/ethanol mixture to obtain 430 mg (56%) of a white solid.

It should be noted that the purification procedure given above was found to be insufficient (vide infra), and therefore both target materials **I** and **II** were further purified. This additional purification step consisted of column chromatography using gradient elution with CHCl3 – 0.8% MeOH in CHCl3 and subsequent crystallisation from ethanol. The gradient elution column chromatography afforded a chemically pure substance while the subsequent crystallisation served as a tool for removal of the trace amount of the opposite enantiomer, which was confirmed by SFC-MS measurements.

1H-NMR (400 MHz, CDCl3): 0.89 (t, 3H, CH3), 1.02 (t, 3H, CH3), 1.23–1.45 (m, 8H, CH2), 1.60 (d, 3H, CH3), 1.79 (m, 2H, CH2), 3.52 (m, 1H, OCH2), 3.69 (m, 1H, OCH2), 4.22 (q, 1H, OCH), 4.28 (t, 2H, OCH2), 7.26–7.30 (m, 5H, Har), 7.70 (d, 2H, *J* = 8.7 Hz, Har), 7.77 (d, 1H, *J* = 3.9 Hz, H 21), 8.26 (d, 2H, *J* = 8.8 Hz, Har). 13C-NMR (100 MHz, CDCl3): 10.46 (CH3), 14.04 (CH3), 18.67 (CH3), 22.13 (CH2), 22.59 (CH2), 25.72 (CH2), 29.73 (CH2), 31.62 (CH2), 66.75 (OCH2), 70.85 (OCH2), 74.97 (OCH), 121.74 (CHar), 122.40 (CHar), 123.84 (CHar), 126.93 (C), 127.40 (CHar), 131.45 (C), 131.90 (CHar), 132.79 (C), 134.22 (CHar), 149.81 (C), 151.12 (C), 154.78 (C), 162.27 (C), 164.15 (C), 171.46 (C). Elemental analysis for C30H34O7S (538.67), calculated C 66.89, H 6.36, S 5.95%, found C 67.02, H 6.44, S 5.86%.

In the similar way, starting from acid **2c**, (*R*)-propyl 5-{4-(4-( 2-hexyloxypropanoyloxy)benzoyloxy) phenyl}thiophene-2-carboxylate (**II**) was prepared, 300 mg (45%). 1H-NMR: (400 MHz, CDCl3): 0.89 (t, 3H, CH3), 1.03 (t, 3H, CH3), 1.24–1.45 (m, 8H, CH2), 1.59 (d, 3H, CH3), 1.79 (m, 2H, CH2), 3.52 (m, 1H, OCH2), 3.69 (m, 1H, OCH2), 4.22 (q, 1H, OCH), 4.27 (t, 2H, OCH2), 7.26–7.30 (m, 5H, Har), 7.69 (d, 2H, *J* = 8.7 Hz, Har), 7.77 (d, 1H, *J* = 3.9 Hz, H 21), 8.26 (d, 2H, *J* = 8.8 Hz, Har). 13C-NMR (100 MHz, CDCl3): 10.46 (CH3), 14.04 (CH3), 18.67 (CH3), 22.13 (CH2), 22.59 (CH2), 25.72 (CH2), 29.73 (CH2), 31.62 (CH2), 66.75 (OCH2), 70.85 (OCH2), 74.97 (OCH), 121.74 (CHar), 122.40 (CHar), 123.84 (CHar), 126.93 (C), 127.40 (CHar), 131.45 (C), 131.90 (CHar), 132.79 (C), 134.22 (CHar), 149.81 (C), 151.12 (C), 154.78 (C), 162.27 (C), 164.15 (C), 171.46 (C). Elemental analysis for C30H34O7S (538.67), calculated C 66.89, H 6.36, S 5.95%, found C 66.54, H 6.37, S 5.92%.

#### **4. Conclusions**

In this study, we focused on the evaluation of optical purity of lactic acid-based building blocks used for the synthesis of a broad range of CLCs (including the target LCs). We have shown that frequently utilised synthetic procedures do not afford enantiomerically pure building blocks. The use of such compounds does not inevitably result in impure target materials; however, very precise control of chemical and optical purity must be employed. Partial racemisation occurring during the synthesis of CLCs could result in modification of mesomorphic properties of the target materials. This may have caused the discrepancies in the mesomorphic behaviour of the same CLCs reported by different research groups. Most importantly, slight modification of enantiomeric composition of the chiral material could potentially lead to malfunctioning of a CLC-based device. Therefore, precise contemporary analytical methods with low limits of detection should be used to secure required quality of CLCs used in research, development and applications.

**Supplementary Materials:** The supplementary information is available online.

**Author Contributions:** A.P. and M.Š. synthesised the materials; T.V., P.T. and D.S. designed and performed HPLC separations, N.K. carried out SFC measurements; M.K. wrote the manuscript, M.K. and D.S. performed final formatting and revision of the manuscript.

**Funding:** The work was supported by Czech Science Foundation (project No. 16-17689Y) and Specific University Research (MSMT No. 21-SVV/2018).

**Conflicts of Interest:** The authors declare no conflicts of interest.

#### **References**


**Sample Availability:** Samples of all the compounds are available from the authors.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

### *Article* **Enhanced Near-Field Chirality in Periodic Arrays of Si Nanowires for Chiral Sensing**

#### **Emilija Petronijevic \* and Concita Sibilia**

Department S.B.A.I., Sapienza Università di Roma, Via A. Scarpa 14, 00161 Rome, Italy; concita.sibilia@uniroma1.it

**\*** Correspondence: emilija.petronijevic@uniroma1.it

Academic Editor: Derek J. McPhee Received: 29 January 2019; Accepted: 27 February 2019; Published: 28 February 2019

**Abstract:** Nanomaterials can be specially designed to enhance optical chirality and their interaction with chiral molecules can lead to enhanced enantioselectivity. Here we propose periodic arrays of Si nanowires for the generation of enhanced near-field chirality. Such structures confine the incident electromagnetic field into specific resonant modes, which leads to an increase in local optical chirality. We investigate and optimize near-field chirality with respect to the geometric parameters and excitation scheme. Specially, we propose a simple experiment for the enhanced enantioselectivity, and optimize the average chirality depending on the possible position of the chiral molecule. We believe that such a simple achiral nanowire approach can be functionalized to give enhanced chirality in the spectral range of interest and thus lead to better discrimination of enantiomers.

**Keywords:** semiconductor nanowires; chirality; enantioselectivity; near-field optical chirality

#### **1. Introduction**

Chirality, a lack of mirror symmetry [1], is an important property of our world governing the behavior of many molecules, enzymes, DNA, and sugars. Optical isomers of the opposite handedness that are non-superimposable images of each other are called *enantiomers*. Specifically, two enantiomers of the same chiral drug have the same chemical structure and physical properties, but different spatial arrangement and optical activity [2], which leads to differences in biological activities such as toxicity [3,4] and enantioselective reactions [5]. Two enantiomers can therefore have extremely different effects on the human body where one can lead to serious side effects [6–8]. Conventionally, polarimetry and circular dichroism (CD) measurements are used to distinguish enantiomers since they differently interact with the circularly polarized (CP) light of the opposite handedness [9]. However, such experiments require high concentrations of enantiomers and long integration times as the intrinsic CD of the molecules is usually extremely low. Therefore, finding novel approaches to detect and recognize low concentrations of enantiomers, thus increasing the sensitivity and reducing the material waste, is of great interest for today's pharmaceutical industry.

In the past decade, the nanoscale photonics community has been dealing with chirality as well: artificial plasmonic nanostructures with broken symmetry were shown to provide a chiral response and CD [10–16]. We recently showed that semiconductor-based nanomaterials, asymmetrically covered by thin metallic layers, can also produce strong CD [17–19]. Merging of the chiral plasmonics with the field of chiral biomolecule enantioselectivity [20] has already given promising results in chiral sensing. For example, in [21], the authors reported on the several orders of magnitude enhancement of the enantiomer detection by means of twisted plasmonic unit cells periodically arranged to form a chiral *metamaterial*. Furthermore, investigation of the near-field effects has opened ways to enhance the interaction between the nanostructure and the chiral molecule via so called *superchiral* fields [22,23]. Namely, for a monochromatic electromagnetic field at frequency ω the optical chirality factor C is defined as:

$$\mathbf{C} = -0.5 \varepsilon\_0 \omega \text{Im} \{ \stackrel{\rightarrow}{\mathbf{E}^\*(\stackrel{\rightarrow}{\mathbf{r}})} \stackrel{\rightarrow}{\mathbf{B}}(\stackrel{\rightarrow}{\mathbf{r}}) \},\tag{1}$$

where <sup>→</sup> <sup>E</sup> and (<sup>→</sup> B) are electric (magnetic) complex field amplitudes. For a plane wave, C is zero for linear polarization, maximum for right circular polarization (RCP), and minimum for left circular polarization (LCP), switching the sign between RCP and LCP. In the near-field of nanostructured materials at the resonance, the electric and magnetic fields can be parallel and out of phase, while their enhancement leads to a C greater than the one of CP, hence the term superchirality. The C factor directly influences the excitation rate of chiral molecules [24] as well as the absorption dissymmetry [25], and its switching of the sign between RCP and LCP is directly connected with the enantioselectivity. Namely, the difference in the absorption rate of two enantiomers can be significantly enhanced if the medium where the mixture exists has an enhanced C. If the medium is excited with CP so that it generates enhanced C of one sign, this will enhance the absorption rate of one enantiomer. Changing the handedness of CP will enhance the absorption rate of another enantiomer, leading to the enhanced difference between the two enantiomers. Finally, in this way the sensitivity of distinction for low enantiomer concentrations can be improved. In general, the medium should produce enhanced C in the volume of the enantiomers, and it must be of the same sign over the volume in order to contribute to the absorption rate of only one enantiomer. Plasmonic nanostructures can be designed to tailor C in the wavelength region of interest for a particular chiral molecule. We recently numerically investigated C enhancement in GaAs nanowires (NWs) asymmetrically covered by Au [26], while in [25,27,28], symmetric nanostructures were shown to give an enhanced near-field C as well. Moreover, in [25] the authors underlined the importance of having only near-field, local chiral effects, without the background chirality of the supporting medium itself. In this way, all the chiral enhancement and corresponding effects arise from the coupling of the chiral molecule with the electromagnetic field in the vicinity of the achiral structure.

In this work, we investigate intrinsically achiral 2D periodic arrays of Si NWs on a Si substrate, a device which is completely symmetric and easy to fabricate. Geometric parameters can be chosen so that these NWs support leaky waveguide modes [29–31] in the visible part of the spectrum. These modes are weakly guided along the NW borders and have a strong field leakage to the surrounding medium, where the evanescent field components can produce a near-field chirality. In [26] we investigated GaAs NW modes at ~800 nm, where we showed that for linearly polarized excitation, the near-field chirality cancels out and the additional symmetry breaking (e.g., the asymmetric layer of Au) must be introduced in order to have a C of prevalently one sign. In [32], NW dimers are used to induce the optical chirality and the hotspots of high C enhancement. Here, we show that under circularly polarized (CP) excitation, achiral NW structure can generate the enhanced chirality in the NW border vicinity, without the additional symmetry breaking which would complicate the processing of a perspective device. For Si NWs, we investigate the influence of geometric parameters on the mode wavelength, which in turn tailors the C distribution; we show that it is possible to spectrally place the enhanced C in the high frequency range of the visible spectrum, technologically relevant for chiral molecules. Further, we investigate the optimization of the average C so that it is distributed in the big part of the volume of the unit cell. For the opposite handedness of the CP excitation, average C changes sign, thus we propose these metasurfaces for enantioselectivity applications, with parameters that can be fixed in the wavelength range of interest. As these materials are easy to fabricate and implement in the existing technology, we believe that this approach can lead to efficient background-free tunable chiral recognition, with decreased waste of materials and increased efficiency.

#### **2. Results**

Structures under investigation are hexagonal Si NWs, that can be patterned on Si substrate, e.g., by means of conventional electron beam lithography [32,33]. In what follows, we use a commercial-grade simulator based on the 3D Finite Difference Time Domain (FDTD) method by Lumerical [34] to simulate complex electromagnetic fields in the Si NW array, and later extract C factor; more details are given in Section 4. The scheme of the simulated device is given in Figure 1a: vertical hexagonal NWs of radius r and length L are periodically arranged with periodicity p in *x* and *y* direction. Such structures have been previously proposed for absorption enhancement, lasing and solar cells, as they can efficiently absorb the visible spectrum wavelengths. The structure is excited by a circularly polarized plane-wave under normal incidence. In Figure 1b we show the absorption spectra dependence on the NW radius, for L = 1000 nm, and p = 400 nm. As expected from theory [35], as well as experiments in [30,31], there is always a fundamental HE11 mode excited for these thin NWs, which leads to the resonant absorption; moreover, with the radius increase, the resonant wavelength of the mode red-shifts. For this periodicity, the mode closely resembles the leaky waveguide mode of the single Si NW. In Figure 1c, the electric field vector in *xz* cross-section of the unit cell is shown for the NW array with parameters r = 50 nm, L = 1000 nm, p = 400 nm, excited at its resonance λ = 525 nm with CP light. Clearly, the electric field keeps circularly polarized behavior, while it experiences enhancement, especially in two regions of the volume corresponding to the antinodes of the Fabry–Perot resonances (due to the boundary conditions at the top and the bottom of the NW). In Figure 1d, we show the electric field intensity enhancement at z = 800 nm *xy* cross-section of the unit cell; there is an obvious leakage of the mode to the surrounding medium, along with a 35-fold increase. In Figure 1e, for the same cross-section, the magnetic field enhancement is even higher, but it remains confined in the NW core. According to Equation (1), the enhanced C can be expected at the points where these field enhancements spatially overlap, while → <sup>E</sup> and <sup>→</sup> H have parallel components out of phase. In the close vicinity of the NW, molecules present in the surrounding medium will experience both electric and magnetic field enhancement, while for the

near-field chirality calculations, their phase difference must be considered as well. Thus, in the following, we investigate C distribution dependence on the NW parameters at the resonant wavelengths; we report on the normalized C\* = C/C0, where C0 is extracted for the RCP excitation of the simulation domain without the Si NWs. For better visualization, we show only the points with |C\*| > 1.2.

**Figure 1.** (**a**) Schematics of the nanowire NW array with quadratic unit cell of periodicity p *x* and *y* directions, and a single NW with diameter D and length L. (**b**) Absorption of the NW arrays with p = 400 nm, and L = 1000 nm, for D = 45–60 nm, for left circular polarization (LCP) excitation. (**c**–**e**) LCP excitation for r = 50 nm at the resonant wavelength λ~525 nm: (**c**) *xz* cross-section of the distribution of the electric field vector; *xy* cross-section of the unit cell at z = 800 nm; (**d**) electric field intensity enhancement; (**e**) magnetic field intensity enhancement.

#### *2.1. Influence of the NW Core Radius*

Firstly, C distribution in the unit cell is investigated for p = 400 nm and L = 1000 nm, for the radii investigated previously. In Figure 2, in all the cases, |C\*| is higher than 5 at the NW borders and remains enhanced in the NW proximity, where the chiral molecules can be deposited for the experiment. More importantly, for RCP (LCP) excitation, C\* keeps the positive (negative) sign of the excitation (normalization by RCP), while having increased values. As the whole domain is achiral, the resonant wavelengths for RCP and LCP are the same. The NW array with r = 45 nm has a resonant wavelength of λ = 493 nm, where Si has higher losses; therefore, the field is efficiently absorbed in the upper part of the NW, and leads to lower electromagnetic field enhancement on the borders closer to the bottom of the NW. For r = 50 nm, we can note that the z positions of the maximum C\* correspond to the antinode enhancements in Figure 1c. With the radius increase leading to the resonance red-shift, the losses of the mode become lower, and C\* spreads more in the unit cell volume; moreover, the second antinodal enhancement of C\* (close to the substrate) also becomes more prominent. Therefore, tuning of the radius can effectively tailor the enhanced C\* in terms of wavelength and 3D distribution. As an example, if the enhanced enantioselectivity experiment involved enantiomers with absorption dissymmetry around 590 nm, the last NW with r = 60 nm should be chosen from these four configurations (the enhanced |C\*| has the highest spread in the unit cell volume).

**Figure 2.** C\* distribution in the unit cell for p = 400 nm, L = 1000 nm, and r = 45–60 nm, at the corresponding NW resonant wavelength for RCP (upper, positive) and LCP (bottom, negative) excitation. The insets show the *xy* top view of each C\* distribution.

#### *2.2. Influence of the NW Array Periodicity*

As the coupling between the neighboring NWs influences the electromagnetic fields, we further investigated the absorption and C\* dependence on the periodicity (Figure 3a) for r = 50 nm and L = 1000 nm. 2D periodic NW arrays are photonic crystals, where, for larger periods, the single NW modes are not considerably influenced by the array coupling [29,35]. However, for denser Si NW arrays, we note a blue-shift of the resonance with the decreasing period; this arises from the destructive coupling between the neighboring NWs due to enhanced near-field evanescent wave interaction. Unfortunately, in Figure 3b, for p = 200 nm, this leads to C\* confinement inside the NW, which is detrimental for the applications where the enantiomers surround the NW in the unit cell. The situation can be optimized by increasing the periodicity, which confines C\* also around the NW (e.g., p = 300 nm

in the middle of Figure 3b, or p = 400 nm in the second graph in Figure 2). Finally, sparse arrays of p = 600 nm have stronger C\* enhancement over the high part of the volume, as it will be shown later. This is due to the strong electromagnetic field enhancement in the near-field medium close to the NW, for the fundamental leaky waveguide modes of the single NW.

**Figure 3.** (**a**) Absorption dependence on the NW array periodicity for r = 50 nm and L = 1000 nm. (**b**) Upper part: C\* distribution in the unit cell for p = 200 nm, p = 300 nm, and p = 600 nm at the corresponding NW resonant wavelengths for RCP excitation; bottom: *xy* top-view of the corresponding distribution from the upper part. Black hexagonal line shows the geometric position of the NW *xy* cross-section. Only RCP excitation is shown as LCP leads to the sign inversion.

#### *2.3. Influence of the NW Length*

For the enhanced enantioselectivity, as previously discussed, the nanostructures can be optimized in order to interact with the enantiomers in the most efficient way, which depends also on the enantiomer position. Therefore, we investigated the NW length influence on C\* distribution, for r = 50 nm and p = 400 nm. In Figure 4a, the modes do not shift with increasing length, but the unitary absorption is reached only for longer lengths. This is rather expected for vertical high refractive index nanowires, where the absorption peak arises due to the mode, which is mainly defined by the radial boundary conditions of the nanowire core (as in dielectric waveguides). Therefore, the radius plays a major role in the spectral position of the absorption peak, while other geometric parameters have a minor influence, as we experimentally demonstrated in [17,18,30,31]. As expected, the shortest NW (L = 500 nm) has an enhanced C\* only due to the first antinode of the resonant mode, while for L = 800 nm another antinode appears. Finally, for L = 1500 nm, three enhanced volume parts are distinguishable; however, the bottom one would not contribute to the enantioselectivity as its C\* is more confined inside the NW. If we consider e.g., the enantiomers with absorption dissymmetry around 525 nm, the best Si NW substrate (with r = 50 nm and p = 400 nm) would be the one with L = 500 nm, and the matrix with chiral molecules should be deposited between z = 0 nm and z = 500 nm. Otherwise, if the NW length is fixed to L = 1500 nm, in order to use zones with the highest C\*, one should deposit another non-absorbing and achiral medium (buffer layer) in the range 0 nm < z < 1000 nm, and then the chiral substance in the range 1000 nm < z < 1500 nm, which complicates the simple approach proposed here.

**Figure 4.** (**a**) Absorption dependence on the NW length for r = 50 nm and p = 400 nm. (**b**) C\* distribution in the unit cell for L = 500 nm, L = 800 nm, and L = 1500 nm at the resonant wavelength of 525 nm. Only RCP excitation is shown as LCP leads to the sign inversion.

#### **3. Discussion**

The overall enantioselectivity enhancement will depend on the percentage of the chiral molecules that are positioned exactly in the part of the volume with enhanced C\*, i.e., in the NW near-field. This is usually not the case for the periodicities that support leaky waveguide modes, so it is important to estimate the average chirality in the unit cell volume, with subtracted NW volume. In order to gain insight into the spectral behavior of the investigated chirality enhancement, we calculate the average normalized optical chirality as:

$$
\widetilde{\mathcal{C}}(\lambda) = \frac{1}{\mathcal{C}\_{RCP}(\lambda)} \frac{\iiint \mathcal{C}(x, y, z, \lambda) dV}{\iiint dV},\tag{2}
$$

where we integrate C across the unit cell as follows: in the *xy* plane, only the parts of the unit-cell outside of the NW core are considered, while in the *z* direction, we investigate two possibilities. First, we integrate in the 0 < z < L range (upper sketch of Figure 5), i.e., total integration. Then, we take into account only the top C\* antinode, integrating in the L/2 < z < L range (bottom sketch of Figure 5), i.e., half-integration, which corresponds to the case when the enantiomers are specially positioned on a buffer layer in order to experience higher C. We approximate that the buffer layer has negligible influence on the C\* distribution, which is valid for low concentrations of chiral molecules, deposited in a solvent which subsequently evaporates. However, generally the buffer layer does change the modal confinement, and the NW array must be reoptimized in terms of r, L and p in order to give enhanced C\* once the optical properties of the buffer layer are known. In Figure 5a, the total integration of L = 1000 nm and r = 50 nm, for the periodicities from 200 nm to 400 nm gives almost no enhancement at the resonant wavelengths, and it is vaguely present only for p = 500 nm (the lowest NW coupling, C- ∼ 1.2). However, the half-integration in Figure 5b improves this difference; here, especially for p = 500 nm, C- reaches almost 2, which is a considerable average enhancement for a 0.5 × 0.5 <sup>μ</sup>m2 surface. For shorter NWs, L = 500 nm and r = 50 nm, the total integration in Figure 5c gives C improvement with respect to Figure 5a, due to inclusion of the part of the space where one antinode generates enhanced C\* (Figure 4b-left). However, this case does not get improved with the half-integration, Figure 4d.

**Figure 5.** Normalized averaged C spectra for r = 50 nm, p = 200–425 nm, and RCP (full lines) and LCP (dashed lines) excitation. Upper and bottom sketches correspond to the integration from z = 0 nm to z = L, and z = L/2 to z = L, respectively. (**a**) L = 1000 nm, total integration; (**b**) L = 500 nm, total integration; (**c**) L = 1000 nm, half-integration; (**d**) L = 500 nm, half-integration.

It is worth noting that for all investigated cases in Figure 5, Si NW arrays give a rather modest average optical chirality. However, we underline the advantage of the use of Si in such nanostructures. Apart from the highly developed technology and perfectly known optical and electrical properties, Si NWs have already been proposed for bio and chemical sensing as the NW surface allows for the immobilization of the investigated substance in the NW near-field, thus affecting the sensor performance and enabling high sensitivity and selectivity [36,37]. For the enhanced enantioselectivity, one should position the chiral molecules in a very thin layer close to the surface which enhances the near-field chirality (a few tens of nm, according to [24]). Many approaches have been found to functionalize the Si nanoparticle surface with molecules [38]. Therefore, the ultimate optimization of the presented approach is the attaching of the chiral species to the NW surface, in the small part of the volume as in the sketch of Figure 6. When the solvent evaporates, a small concentration of chiral molecules which remain attached to the Si surface introduces a negligible change in the NW environment, so that the molecules experience the near-field chirality of the resonant modes presented above. Next, we focus on the best case from Figure 5b, i.e., r = 50 nm, L = 1000 nm, and p = 500 nm, which gave the C- peak at 542 nm. In Figure 6 we show the *xy* cross-section of the C\* distribution at the resonance and at the z position of the C\* antinode, for RCP and LCP excitation (we omit C\* inside the NW as it is not important for the interaction with the enantiomers). There is a 36-fold C enhancement at the NW borders, and the chiral molecules in the dashed circles experience the average C at least on the order of 20, which will finally lead to significantly higher enhancement with respect to the approach in Figure 5c. Therefore, one can smartly functionalize Si NW sidewalls so that the enantiomers are positioned at points with maximum C\*.

**Figure 6.** Left: sketch of the Si NW functionalization with bonded chiral substance for the improvement of enantioselectivity. Right: xy cross-section of C\* distribution at the antinode of the NW with r = 50 nm, L = 1000 nm, and p = 500 nm (resonant wavelength at 542 nm) for RCP and LCP excitation. Dashed circles represent the volume of the enantiomers attached to the NW surface.

#### **4. Materials and Methods**

FDTD simulations solve the Maxwell's equations over discrete spatial and temporal grid, and give as a result complex electromagnetic fields in the unit cell consisting of one Si NW in the middle. Si NW lie on a Si substrate, which is considered semi-infinite for z < 0; for z > 0, the medium is air. Optical properties of Si were taken from the Lumerical database. In the *z* direction, perfectly matched layers (PML) were placed at least half the maximum wavelength from the top and bottom of the NW to ensure the numerical stability. For the normal incidence excitation, a plane-wave source was used from the top side (negative *z* direction in Figure 1a), and periodic boundary conditions were applied in the *xy* plane. Circular polarization was simulated as a combination of two orthogonal sources with a phase difference of ±90◦. Total absorption of the NW was simulated by integrating the absorption per unit volume <sup>σ</sup>abs over the NW volume; <sup>σ</sup>abs was calculated from <sup>σ</sup>abs <sup>=</sup> −0.5ω2|E|2Im{ε}, from the electric field and complex refractive index monitors across the NW domain. Electric and magnetic field confinements were monitored by a cross-section field profile monitor in the *xz* and *xy* planes. C factor was extracted from a 3D field profile monitor encompassing the whole unit cell in the *xy* plane, and having a z span from 0 nm to the NW length. The calculated near-field chiral properties arise from electromagnetic field confinement of the NW modes, and are not an intrinsic property of molecules. Moreover, approximation of air as a medium surrounding the NWs is valid for low concentrations of chiral molecules deposited in the solution which evaporates, leaving the molecules in the NW vicinity. In future work, the experimental proof of principle will be done for chiral molecules that have intrinsic circular dichroism at the modal resonances of a chosen Si nanowire array.

#### **5. Conclusions**

In this work, we have proposed a path to enhanced near-field optical chirality by means of symmetric Si NW arrays, which support leaky waveguide modes that enhance the near-field optical chirality of CP excitation in the shorter wavelength part of the visible spectrum, which is of interest for many chiral molecules. The C enhancement can be optimized by choosing the wavelength range where enantiomers show CD, setting the radius, length and period of the NW array so that it gives resonances in that range, and optimizing the molecules position. Such an achiral approach does not suffer from the background chiral behavior present in intrinsically or extrinsically chiral plasmonic nanomaterials, and the absorption dissymmetry arises only for the near-field effects. Moreover, the use of conventional Si technology enables the functionalization of the NW surface which greatly enhances the overall chirality. We believe that this simple approach can lead to Si nanostructures-governed applications in enhanced enantioselectivity.

**Author Contributions:** Conceptualization, E.P. and C.S.; methodology, E.P.; software, E.P.; validation, C.S.; formal analysis, E.P.; investigation, E.P.; resources, C.S.; data curation, E.P.; writing—original draft preparation, E.P.; writing—review and editing, C.S.; visualization, E.P.; supervision, C.S.; project administration, C.S.; funding acquisition, C.S.

**Funding:** The authors have no funding to report.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


**Sample Availability:** Samples of the compounds are not available from the authors.

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