S S symmetry Review Actual Symmetry of Symmetric Molecular Adducts in the Gas Phase, Solution and in the Solid State Ilya G. Shenderovich Institute of Organic Chemistry, University of Regensburg, Universitaetstrasse 31, 93053 Regensburg, Germany; [email protected] Abstract: This review discusses molecular adducts, whose composition allows a symmetric structure. Such adducts are popular model systems, as they are useful for analyzing the effect of structure on the property selected for study since they allow one to reduce the number of parameters. The main objectives of this discussion are to evaluate the influence of the surroundings on the symmetry of these adducts, steric hindrances within the adducts, competition between different noncovalent interactions responsible for stabilizing the adducts, and experimental methods that can be used to study the symmetry at different time scales. This review considers the following central binding units: hydrogen (proton), halogen (anion), metal (cation), water (hydrogen peroxide). Keywords: hydrogen bonding; noncovalent interactions; isotope effect; cooperativity; water; organ- ometallic complexes; NMR; DFT 1. Introduction If something is perfectly symmetric, it can be boring, but it cannot be wrong. If Citation: Shenderovich, I.G. Actual something is asymmetric, it has potential to be questioned. Note, for example, the symmetry Symmetry of Symmetric Molecular of time in physics [1,2]. Symmetry also plays an important role in chemistry. Whether Adducts in the Gas Phase, Solution it is stereochemistry [3], soft matter self-assembly [4,5], solids [6,7], or diffusion [8], the and in the Solid State. Symmetry 2021, dependence of the physical and chemical properties of a molecular system on its symmetry 13, 756. https://doi.org/10.3390/ is often a key issue. Symmetric molecular adducts are popular model systems; they are sym13050756 used to analyze the effect of structure on the property chosen for research since they allow one to reduce the number of parameters [9–12]. On the other hand, symmetry in chemistry Academic Editor: Enrico Bodo is a matter of the size and time scale in question [13]. The same molecular system can be symmetric for one experimental method and asymmetric for another. It is important to Received: 9 April 2021 understand what processes are hidden behind this discrepancy in each specific case. Accepted: 22 April 2021 Published: 27 April 2021 The problem of the size scale already begins at the level of the model adducts composi- tion. What structure has the simplest model adduct with which it is possible to investigate + + Publisher’s Note: MDPI stays neutral the property under consideration? The Zundel cation (H5O2 ) and the Eigen cation (H9O4 ) with regard to jurisdictional claims in seem to be the most illustrative example [14,15]. Which of these two structures is the best published maps and institutional affil- for simulating a hydrated proton? It seems that neither experiment nor theory can answer iations. this question regardless of the property being discussed [16–20]. The same is valid for the hydration of the hydroxide ion [21–24]. Of course, bulk water is one of the most complex solvents in this content. The time scale problem has to do with tautomerism. For some methods, its rate is slow. In this case, experimental parameters can be observed for each of the structures presented. For other methods, this rate is fast and only average experimental Copyright: © 2021 by the author. Licensee MDPI, Basel, Switzerland. parameters can be observed. This article is an open access article This short review discusses molecular adducts whose composition allows a symmetric distributed under the terms and structure. These adducts should be stable in organic solvents at least on the millisecond conditions of the Creative Commons time scale. It should be possible to model the effect of the surroundings on their structure Attribution (CC BY) license (https:// by considering the environment as a polarizable continuum. It is not limited only to creativecommons.org/licenses/by/ the polarizable continuum model (PCM) and solvation model based on density (SMD) 4.0/). approximations [25–29]. It is important that the solute–solvent interactions do not have to Symmetry 2021, 13, 756. https://doi.org/10.3390/sym13050756 https://www.mdpi.com/journal/symmetry Symmetry 2021, 13, 756 2 of 23 be considered explicitly. Some examples of the molecular dynamics (MD) studies will be included as well [30–32]. If known, the symmetry of the selected adducts in the gas phase and solids is also discussed. The main objectives of this review are to discuss (i) the influence of the environment on the symmetry of these adducts, (ii) steric hindrances caused by interactions within the adducts, (iii) competition between different noncovalent interactions responsible for stabilizing the adducts, and (iv) what experimental methods can be used to study their symmetry at different time scales. Therefore, this review is not structured according to the type of interaction that is responsible for the stabilization of the adducts, but according to the central binding unit: hydrogen (proton), halogen (anion), metal (cation), water (hydrogen peroxide). Symmetry 2021, 13, x FOR PEER REVIEW 3 of 24 2. Hydrogen (Proton) as the Binding Unit Hydrogen bonding (H-bond) is one of the most important tools for controlling molecu- larto the conformation dissociation and of intermolecularthe ion pair. On aggregation. the other hand, A large the solvation number of of potentially the two C=O symmetric moieties structuresof the maleate of (AHA) anion- byand water (BHB) is+ symmetrictypes is known. only on Here, average a few due of to the a rapid more change typical in ones the arestructure discussed. of the solvation shell caused by the thermal motion of solvent molecules. In organic solvents the anion–cation interaction cannot be neglected. It is reasonable that, 2.1.with Intramolecular the exception H-Bonds of very bulky cations, it is this interaction that will determine the symmetryFigure 1of shows the H-bond. selected For molecules the bulky with cations, an intramolecular the solute–solvent H-bond. interactions The lowest energybecome geometrycritical again. of 3-carboxypropanoate The effect of such interactions (the maleate on anion, the geometry Figure1a) of in H-bonds the gas phaseshould has not an be asymmetricunderestimated H-bond. [49]. TheIt is OH likely and that H··· Oat distancesany given are moment 1.33 and of 1.10 time Å [the33]. H-bond However, in thethe zero-pointmaleate anion energy is asymmetric is above the in energy any solvent barrier and for proton that its transfer. C=O moieties Consequently, play an dueimportant to the motionrole in ofthis. the Note mobile that proton the intramolecular in the ground H-bonds vibrational of state,hydrogen the H-bond succinate, is symmetric meso-/rac-2,3- [34]. Asdimethylsuccinate, a result, this molecule and (R)-(+)-methylsuccinate yielded a broad and featureless are asymmetric photoelectron in CDF spectrum3/CDF2Cl [50]. [33]. FigureFigure 1.1. PotentiallyPotentially symmetricsymmetric structures structures with with intramolecular intramolecular H-bonding. H-bonding. 3-carboxypropanoate 3-carboxypropanoate (a ), 2-carboxybenzoate(a), 2-carboxybenzoate (b), 1,8-bis(di-R-amino)-naphthalene-H(b), 1,8-bis(di-R-amino)-naphthalene-H+ (c),+ 1,8-naphthyridine-H(c), 1,8-naphthyridine-H+ (d).+ (d). TheReference symmetry [51] ofreviews the maleate the symmetry anion in solutionof the H-bond was studied of the using maleate a primary anion H/Dwith p isotopedifferent effect cations on the in the NMR crystalline chemical phase. shift, UsinD(H/D)g the≡ positionδ(ADB) of− theδ(A mobileHB). The proton motion available of the bindingfrom low-temperature hydron within a neutron-diffraction H-bond should always studies be treated on nine as quantumdifferent [35hydrogen]. Consequently, maleate whensalts the[52–57], mobile the proton authors issubstituted established for a deuteron,correlation the that geometry allows of determination the H-bond changes. of this Forposition a symmetric from X-ray H-bond diffraction this substitution (XRD) data results[51,58]. inThere a contraction are three groups of the heavyof crystals nuclei in distance,which the that deviation is, the strengtheningof the proton position of the H-bond; from the for H-bond an asymmetric center is below H-bond 0.06 it causesÅ, about a lengthening0.2 Å, and about of this 0.3 distance, Å [51]. The that symmetry is, the weakening of these H-bonds of the H-bond changes [36 under]. These pressure geometric [59]. p changesSimilar lead toresults chemical have shift been changes. obtained It is expectedfor hydrogen that Dphthalate,(H/D) > 0Figure for symmetric 1b. Its H-bondsintramolecular and negative H-bondfor is asymmetricsymmetric in ones the (note, gas phase that other [60]. authorsIn solution may it define becomes the δ − δ p isotopeasymmetric effects due as to(AHB) solute–solvent(ADB)) and [37 anion–ca]. For thetion maleate interactions anion [60–63].D(H/D) Note = 0.08 that ppm the at 150 K [38] in an aprotic, highly polar CDF /CDF Cl mixture [39] and 0.03 ppm at strength of this H-bond suffers from significant3 steric 2stress [64]. The energy of this bond 218 K in CD Cl [40]. These results suggested that under these conditions this H-bond in crystalline2 phthalic2 acid is only 9.5 kJ/mol [65] while it can be more than 100 kJ/mol for strong intermolecular H-bonds [66]. In the crystalline phase, the position of the mobile proton within the intramolecular H-bond of lithium hydrogen phthalate depends on the environment and can be both very close to the center and very asymmetric [67]. However, there does not appear to be a crystalline hydrogen phthalate with a perfectly symmetric intramolecular H-bond [68]. The symmetry of the intramolecular H-bond in 1,8-bis(dimethylamino)naphthalene- H+ (Figure 1c) has been recently discussed in detail [69].