Natural Deep Eutectic Solvents: Properties, Applications, and Perspectives

Abstract

As functional liquid media, natural deep eutectic solvent (NADES) species can dissolve natural or synthetic chemicals of low water solubility. Moreover, the special properties of NADES, such as biodegradability and biocompatibility, suggest that they are alternative candidates for concepts and applications involving some organic solvents and ionic liquids. Owing to the growing comprehension of the eutectic mechanisms and the advancing interest in the natural eutectic phenomenon, many NADES applications have been developed in the past several years. However, unlike organic solvents, the basic structural unit of NADES media primarily depends on the intermolecular interactions among their components. This makes NADES matrices readily influenced by various factors, such as water content, temperature, and component ratio and, thus, extends the metabolomic challenge of natural products (NPs). To enhance the understanding of the importance of NADES in biological systems, this review focuses on NADES properties and applications in NP research. The present thorough chronological and statistical analysis of existing report adds to the recognition of the distinctiveness of (NA)DES, involves a discussion of NADES-related observations in NP research, and reportes applications of these eutectic mixtures. The work identifies potential areas for future studies of (NA)DES by evaluating relevant applications, including their use as extraction and chromatographic media as well as their biomedical relevance. The chemical diversity of natural metabolites that generate or participate in NADES formation highlights the growing insight that biosynthetically primordial metabolites (PRIMs) are as essential to the biological function and bioactivity of unrefined natural products as the biosynthetically more highly evolutionary metabolites (HEVOs) that can be isolated from crude mixtures.

Figure 1

Schematic diagram of the eutectic point on a two-component (1 and 2) phase, where EC means eutectic component. The dashed curve represents the melting points of a binary NADES family under different molar ratios. All unified liquid media are located in A, while applied NADES species are at or under ambient temperature as a part of A. This area should be the shape of a del operator, for which one angle point in the valley is the eutectic point. B and C represent the mixtures of EC1 and EC2 (solid/liquid or liquid/solid), and D is a mixture of EC1 and EC2 (solid/solid). The eutectic point is remarkable in that two or more compounds may combine in precise and fortuitous proportions to become mutually compatible in such as way that dramatically lowers the melting point of the mixture.

Figure 2

Number of publications on key topics since 1950: eutectic (● in blue, 1700 items), eutectic mixture (■ in orange, 652 items), deep eutectic solvent (× in gray, 224 items), and natural deep eutectic solvent (+ in yellow, 37 items). The analyzed data were retrieved from PubMed (National Center for Biotechnology Information, NCBI) on November 7, 2016. The bottom shows the chronological milestone eutectic events.

Figure 3

Water loss study on the transition from NADES solution to NADES state. (A) Evaporation of neat distilled water (●; A) and a NADES composed of mannose (0.01 mol), dimethyl urea (0.025 mol), and distilled water (2 mL) (■; B and C) via vacuum centrifugal evaporation. The drying curve of the mannose–dimethyl urea–water NADES is split into a rapid drying zone (initial stage of B) during the first 7 h and the slower, asymptotic loss of water from 12 to 18 h (C). Both time zones exhibit a linear correlation between time and water loss.

Figure 4

Distribution (percentage, %) of the component molar ratios (mol/mol) in reported NADES.^,,,

Figure 5

Kinetic energy models for a binary NADES (A, temperature administration) and a ternary aqueous system (B, water content administration). As entropy rises, the strength of intermolecular bonding decreases, which subsequently impacts the relevant physical parameters.

Figure 6

Quantitative ¹H NMR spectrum (360 MHz) of licochalcone A (A) vs the same compound purified by countercurrent separation (B) (DMSO-d₆, 60 s relaxation delay [D1]). The image insets show the physical appearance of corresponding samples, especially the liquid nature of the otherwise “pure” licochalcone A in sample (B).