nanomaterials Article Enantioselective Self-Assembled Nanofibrillar Network with Glutamide-Based Organogelator Nao Nagatomo 1 , Hisashi Oishi 1 , Yutaka Kuwahara 1 , Makoto Takafuji 1, * , Reiko Oda 2 , Taisuke Hamada 3 and Hirotaka Ihara 1,3, *   Citation: Nagatomo, N.; Oishi, H.; Kuwahara, Y.; Takafuji, M.; Oda, R.; Hamada, T.; Ihara, H. Enantioselective Self-Assembled Nanofibrillar Network with Glutamide-Based Organogelator. Nanomaterials 2021, 11, 1376. https://doi.org/10.3390/nano 11061376 Academic Editor: Lennart Bergström Received: 29 April 2021 Accepted: 19 May 2021 Published: 23 May 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 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 (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Applied Chemistry and Biochemistry, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan; kumacats01@gmail.com (N.N.); kumacats02@gmail.com (H.O.); kuwahara@kumamoto-u.ac.jp (Y.K.) 2 Institut de Chimie & Biologie des Membranes & des Nano-objects, CNRS, 33607 Pessac, France; reiko.oda@u-bordeaux.fr 3 National Institute of Technology, Okinawa College, 905 Henoko, Nago, Okinawa 905-2192, Japan; hamada@okinawa-ct.ac.jp * Correspondence: takafuji@kumamoto-u.ac.jp (M.T.); ihara@kumamoto-u.ac.jp (H.I.); Tel.: +81-96-342-3662 (M.T. & H.I.) Abstract: A chiral molecular gelation system, as a chiral host, was used to effectively realize enan- tioselectivity using the simple carboxylic acid functional group. For this purpose, an L-glutamic-acid- based lipidic amphiphile (G-CA) with a carboxylic head group was selected and its responsiveness to cationic guest molecules was investigated. The dispersion morphology of G-CA in its solution state was examined by confocal and transmission electron microscopies, while interactions between the G-CA, as the host system, and guest molecules were evaluated by UV-visible, circular dichroism, and fluorescence spectroscopies. As a result, enantioselectivity was effectively induced when G-CA formed highly ordered aggregates that provide negatively charged surfaces in which carboxyl groups are assembled in highly ordered states, and when the two cationic groups of the guest molecule are attached to this surface through multiple interactions. Keywords: molecular gel; nanofibril; self-assembly; secondary chirality; enantioselectivity; circu- lar dichroism 1. Introduction Chiral molecules are the basis of life [1]. Primary chirality is amplified to higher chirality by the precise orientations and arrangements of molecular chiral units, which produces a variety of life-based phenomena. In synthetic chemistry, chiral synthesis and chiral separation are still evolving as universal research tools, with supramolecular organogels attracting attention as media for chiral separation in recent years. Such gelation, unlike partially crosslinked polymer gelation, is characterized by the formation of a three- dimensional network through one-dimensional growth involving molecular aggregates of small chiral molecules, such as amino acids [2–5] and other chiral organic sources [6–9]. Therefore, such gels are very attractive in that they form highly ordered chiral orientations that are difficult to obtain using common polymer gels. The first examples of chiral separation using organogels were reported as enantioselec- tive transport phenomena of amino acid derivatives from gels to aqueous phases [10]. Since then, most of the remarkable enantioselectivities obtained using chiral organogels have been realized by the introduction of special supramolecular or multi-functional groups, such as a porphyrin [11,12], a pyridylpyrazole [13], and a quinolinol [14] into a molecule. In this study, we aimed to induce enantioselectivity through amplification of chirality using simple functional groups in a manner that does not rely on a supramolecular functional group. Inducing enantioselectivity using a carboxyl group as the simplest functional group was the main challenge of this study (Figure 1). Nanomaterials 2021, 11, 1376. https://doi.org/10.3390/nano11061376 https://www.mdpi.com/journal/nanomaterials