**1. Introduction**

NH ... O,S,N (in the following called NH ... X for simplicity) intramolecular hydrogen bonds are very important building blocks in biomolecules, in self-organizing materials, in drugs, in switching molecules and in chemistry as such. Examples are given in this review. As the title indicates, this review is dealing with intramolecular hydrogen bonding. Recent reviews cover this subject [1,2]. Review [1] concentrates on Schiff bases made from salicylaldehyde and TRIS. Rules are set up to predict the predominant tautomer based on linear free energy relationships. Review [2] is focused on aromatic systems such as *o*-hydroxy Schiff bases and Mannich bases and mainly deals with tautomerism. However, in order to make it feasible within the limits of a review of this type, tautomeric systems as such are not dealt with. Nevertheless, NH ... X systems are of course one of the two forms of a tautomeric system involving NH and may as such provide useful information in the study of tautomeric systems. Older reviews covering hydrogen bonding and tautomeric systems can also be found [3–5]. Energetics are also treated and in that relation the question of hydrogen bond strength will be touched upon. The title may be misleadingly broad. By spectroscopic techniques NMR and infrared spectroscopy are primarily meant, as they are central in these studies. Within NMR, 1H-, 13C- and 15N-chemical shifts, isotope effects on chemical shifts, one-bond NH and long-range coupling constants are included, whereas for IR spectroscopy mainly NH stretching frequencies are explored. Theoretical calculations are included in cases when they supplement experimental results although they are not the focal point for this review. A goal is to give some guidance to which spectroscopic tool to use in a given situation. NH ... X hydrogen bonds have been investigated less than OH...Xintramolecularhydrogenbonds.Foranoverviewofthelatter,see[6].

Intramolecular hydrogen bonds can be quite different, as seen in Figures 1 and 2. An important feature is the linker between the NH donor and the hydrogen bond acceptor. If this is a double bond or part of an aromatic system, the system has been termed resonanceassisted hydrogen bonding (RAHB) [6] and this clearly influences the type and the strength of the hydrogen bond. In other cases, e.g., proteins, intramolecular hydrogen bonds are not

**Citation:** Hansen, P.E. A Spectroscopic Overview of Intramolecular Hydrogen Bonds of NH . . . O,S,N Type. *Molecules* **2021**, *26*, 2409. https://doi.org/10.3390/ molecules26092409

Academic Editor: Mirosław Jabło ´nski

Received: 4 January 2021 Accepted: 18 April 2021 Published: 21 April 2021

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very different from intermolecular ones, except for the fact that the protein may be keeping the donor and the acceptor close to each other. This type of hydrogen bond is clearly very important in proteins, both in defining α-helices, β-sheets and turns. In proteins many hydrogen bonds may be present. Therefore methods to identify specific pairs and to characterize the individual hydrogen bonded pairs is needed. For DNA and RNA the hydrogen bonds are very similar.

**Figure 1.** Intramolecular hydrogen bond scheme of RAHB type or charge assisted type. The bond between the α- and the β-carbon can be a double- or an aromatic bond. (**A**) R, R',R"=H, alkyl or aryl; X=H, C, O, N or S. (**B**) R, R´,R"=H, C,O,N; X=H or alkyl or aryl. (**C**) R=H or C; X=H or C or OR. (**D**) R, R´and R"=H or alkyl or aryl; X=lone pair or O− (nitrogen is positively charged, as it is a nitro group). (**E**) R, R´ and R"=H or alkyl or aryl; X=alkyl or aryl. (**F**) R, R´ and R"=alkyl or aryl; X + R'=benzene ring. (**G**) R, R´and R"=alkyl. (**H**) R and R´=alkyl, X=Ph.

**Figure 2.** Non-RAHB system. The left hand molecule with X=N(CH3)2 is the well known DMANH+ proton sponge. With X=pyrrole in Figure 4 hydrogen bonding to the π-electron system is found, [7] whereas with X=N(CH3)C=OCH3 hydrogen bonding to nitrogen have been tested [8]. The right hand molecule, N,N,N"-tris(p-tolyl)azacalix [3](2,6)pyridine (TAPH), shows an extremely low field NH proton chemical shift of 22.1 ppm [9,10].

In the following, a number of typical hydrogen bond donors and acceptors and pairs of these are compared. It is of course not possible to mention all compounds with intramolecular NH hydrogen bonds. General trends will be given together with typical examples.
