Smart Molecular Recognition: From Key-to-Lock Principle to Memory-Based Selectivity

MINI REVIEW published: 21 January 2020 doi: 10.3389/fchem.2019.00933 Smart Molecular Recognition: From Key-to-Lock Principle to Memory-Based Selectivity Askar K. Gatiatulin, Marat A. Ziganshin and Valery V. Gorbatchuk* Department of Physical Chemistry, A. M. Butlerov Institute of Chemistry, Kazan Federal University, Kazan, Russia The formation and decomposition of inclusion compounds with a solid-solid phase transition may be very selective to the guest molecular structure. This selectivity may function in essentially different ways than defined by the classical concept of molecular recognition, which implies the preferential binding of complementary molecules. Solid inclusion compounds may take part as an initial or/and final state in several processes of different types summarized in this review, which selectivity is boosted by cooperativity of participating molecular crystals. Some of these processes resemble switching electronic devices and can be called smart giving practically absolute molecular recognition. Keywords: molecular recognition, selectivity, inclusion compound, clathrate, phase transition Edited by: Yong Yao, Nantong University, China Reviewed by: Pi Wang, Taiyuan University of Technology, China Lin An, Xuzhou Medical University, China *Correspondence: Valery V. Gorbatchuk Specialty section: This article was submitted to Supramolecular Chemistry, a section of the journal Frontiers in Chemistry Received: 27 November 2019 Accepted: 23 December 2019 Published: 21 January 2020 Citation: Gatiatulin AK, Ziganshin MA and Gorbatchuk VV (2020) Smart Molecular Recognition: From Key-to-Lock Principle to Memory-Based Selectivity. Front. Chem. 7:933. doi: 10.3389/fchem.2019.00933 Frontiers in Chemistry | www.frontiersin.org INTRODUCTION Molecular recognition of neutral molecules is one of the key problems in chemical technologies and in analytical and biotechnological applications (Reinhoudt, 2013; Persch et al., 2015; Shu et al., 2018). To reach a sufficient selectivity, host compounds with very complex structure are synthesized (Ariga et al., 2012; Zhang et al., 2019) to fit the well-known key-to-lock concept of molecular recognition formulated by Fischer (1894). This concept later developed in supramolecular chemistry is based on complementarity of two interacting molecules, where the host interacts with guest cooperatively through several more or less strong coordinate, donor-acceptor, and hydrogen bonds having a specific spatial arrangement (Joyce et al., 2010; Sonnenberg et al., 2012). The most studies of molecular recognition are conducted in liquid solutions (Ariga et al., 2012; Persch et al., 2015; Shu et al., 2018; Zhang et al., 2019) and perform a sufficient selectivity only if guest forms at least two such bonds with host (Yao et al., 2018). This review describes the possible alternatives to the classical key-to-lock principle with a higher selectivity of molecular recognition. These alternatives are based on cooperativity of phase transitions, which adds up the small differences in molecular structure of different included guests. Some of the described recognition principles can be called smart because they resemble the function of electronic devices. Quantitatively, the cooperativity of phase transition at guest inclusion by solid host can be seen in a stepwise sigmoidal shape of guest sorption isotherm (Gorbatchuk et al., 1997a; Dewa et al., 1998). According to the Gibbs phase rule, a sorption isotherm in system with two independent components (guest and host) should have a threshold concentration, vapor pressure or thermodynamic activity of guest corresponding to formation of three phases of guest, host,and clathrate (inclusion compound) at constant temperature, Figure 1A (Gorbatchuk et al., 2002). Below this threshold activity, the guest is not included, and below and above this threshold the composition of the solid phase does not change. 1 January 2020 | Volume 7 | Article 933 Gatiatulin et al. Smart Molecular Recognition FIGURE 1 | Stepwise inclusion selectivity of solid hosts. (A) Stepwise selectivity by inclusion Gibbs energy; (B) crystallization selectivity of an amorphous host; (C) stepwise size exclusion effect; (D) inversed size exclusion effect (“anti-sieve”). In solid state, this phase transition is observed if the initial host is non-porous (Gorbatchuk et al., 2002). If the host has a permanent porosity combined with flexible structure, like that of some metal organic frameworks (MOFs) (Hiraide et al., 2016; Engel et al., 2017) or silicalites (DeJaco et al., 2019), the initial part of sorption isotherm may have the shape of Langmuir isotherm followed by a sigmoidal step. This step is called the gate-opening or breathing (Afonso et al., 2012; Lee et al., 2019). A similar cooperative phenomena were observed for biological objects, e.g., for oxygen binding by aqueous solution of hemoglobin (Yuan et al., 2015). The sigmoidal isotherms of guest inclusion by solid host and related cooperativity of guest release from the inclusion compound may boost the selectivity of these processes. Depending on the initial and final states of host, several specific types of selectivity may be observed, which are described in this review. using an atomic force microscopy for thin amorphous films of dipeptides (Ziganshin et al., 2015). Amorphous dipeptides may have three options in contact with guest vapors depending on the guest molecular structure: (1) crystallization, (2) gel formation, (3) intact host morphology (Ziganshin et al., 2017). The amorphous calixarenes in the form of a compact transparent glass can be used to detect visually the composition of a binary guest mixture, where only one (good) component has an ability to induce the host crystallization. The mixture should have the concentration of this guest above a certain threshold value for this crystallization to be apparent, Figure 1B. For example, glassy tert-butylthiacalix[4]arene derivative crystallizes in contact with vapors of the aqueous solution of ethanol if its concentration is above 24 vol.% (Gataullina et al., 2015). The glass of the same calixarene in another conformation allows detecting 1% vol. of benzene in hexane (Gataullina et al., 2017). A similar crystallization behavior was observed for glassy polymers (Gao et al., 2012), which have a less pronounced concentration threshold for the good component in binary solvent due to the incomplete crystallization. CRYSTALLIZATION SELECTIVITY OF AMORPHOUS HOST SELECTIVITY BY CAPACITY AND GIBBS ENERGY OF GUEST INCLUSION Selectivity of guest inclusion may be visualized if the initial state of host is amorphous. The amorphous state is a high-energy state, so its transition to the crystalline state may be spontaneous (Faizullin et al., 2019). The activation of this process with guest vapors may be selective. Such selectivity was observed visually for a compact glass of calixarene (Gataullina et al., 2015, 2017) and Frontie (...truncated)