Current Organic Chemistry - Volume 13, Issue 3, 2009

Polyphenols are a very diverse class of compounds. In the present volume the emphasis is on Schiff bases and azo compounds containing one or more hydroxy group. Such polyphenols have many interesting properties and uses. Photochromism is an extremely important feature to be used in many context in society. o-Hydroxy Schiff bases show this feature in a number of cases. A model for the process is now suggested. X-ray crystallography is providing unique information about tautomeric equilibria in the solid state, when experiments are done at variable temperatures. The detailed informations allow a characterization of the features favouring one form over the other. Infra Red spectroscopy is a very important tool in the study of tautomeric systems with intramolecular hydrogen bonds. Anharmonicity is central to this class of compounds and related to that bandwidths. Polarization of bonds is another central feature. Schiff bases are very important in a number of biological reactions, not the least in vision. For such complex systems, the use of chemometric methods is invaluable.

The main problem in the quantitative analysis of tautomeric compounds is that the individual tautomers cannot be physically separated. As a result, quantitative analysis, which requires calibration, is in general impossible. This is a general problem for molecular spectroscopy and gives rise to many chemometric approaches for the treatment of existing spectral data, all of them developed to overcome the lack of individual spectral data for the pure, individual, tautomers. The reliability of these approaches depends strongly on the mathematical and spectral approximations used. Therefore the aim of the current review is to describe and compare critically the most frequently used methods for the processing of spectral data of tautomeric systems. Such data are usually obtained by absorption spectroscopy (UV-Vis, Fl and sometimes IR) and NMR in solution, but, in addition, some attempts for quantitative analysis in gas phase by mass spectrometry are considered.

In many cases, the cofactors of biologically important proteins are linked to their apoproteins by Schiff bases. In this review we discuss three classes of proteins in which Schiff bases are crucial for their function and catalytic mechanisms. First, we focus on retinylidene proteins, in which the cofactor retinal is fixed to the apoprotein by a protonated Schiff base. Light induced retinal isomerization triggers a photocycle or a cascade of structural changes in which deprotonation of the Schiff base is a crucial step. We compare the photocycles of archaeal type rhodopsins, channelrhodopsins and the light induced cascades of visual rhodopsins. Pyridoxal phosphate (PLP) dependent enzymes are summarized in the second section. In these proteins, the cofactor PLP is linked via a Schiff base to the side chain of a lysine. In most cases, hydrolysis of this linkage is critical for substrate binding. Finally, aldolases, that catalyze aldol cleavage during glycolysis, contain a lysine residue at their active center. Formation of a protonated Schiff base linkage to a carbonyl group of the substrate is the first step of the catalytic mechanism. This will be discussed in the last section.

This review reports a systematic investigation, carried out on the Cambridge Crystallographic Database (CSD), on the structural features of iminoalkyl-phenols (or naphthols) as well as azo-phenols (or naphthols). All these compounds form N-H…O/O-H…N intramolecular hydrogen bonds assisted by resonance (RAHB) in tautomeric equilibrium which can be finely tuned by the substituents. Accordingly, they can present reversible proton transfer leading to interesting properties such as thermochromism and photochromism. The phenol derivatives 2-(1-aryliminoalkyl)phenols and 2- arylazophenols display the predominance of the O-H…N form. Furthermore, they display the following features: i) strongly electron-donating substituents in p-position on the N-phenyl group shorten the N…O contact distance but not enough to produce the O-H…N to O-H…N/N-H…O transition; ii) such a transition can be however induced by strongly electron-withdrawing substituents at the phenol ring which increase the phenol acidity; iii) very similar effects are determined by intermolecular hydrogen-bonded O-H…O contacts with the phenolic oxygen which, stabilizing the N-H…O bond produce the O-H…N to O-H…N/N-H…O transition and, sometimes, the complete proton transfer to the pure NH… O form. The naphthol derivatives (1-(1-aryliminoalkyl-2-naphthols and 1-arylazo-2-naphthols) display the most interesting situation of two roughly isoenergetic O-H…N/N-H…O tautomers which can be tuned by modifying the Nsubstituent, the effects of substitution at the N-phenyl moiety being by far the most extensively studied. The structures of variously aryl-substituted 1-(1-aryliminoalkyl)-2-naphthols, though collected only at room temperature, indicate that almost all of them are tautomeric equilibria, even if full information on proton populations and dynamic or static nature of the proton disorder are not available. Conversely, the structures of a series of aryl-substituted 1-arylazo-2-naphthols have been recently determined at variable temperature showing that strongly electron-attracting substituents stabilize the pure N-H…O form, while substituents with increasing electron-donating properties transform the system into a dynamic, or static, N-H…O → ↞ O-H…N tautomeric equilibrium in the solid with an ever increasing population of the O-H…N azoenol tautomer.

Schiff bases of salicylaldehyde with amines (anils) comprise a chemical system undergoing hydrogen-atom tautomerism between enol and keto forms and show the phenomena of solid state photochromism and thermochromism. However, the photochromic phenomenon is exhibited not only in the crystalline state but in solution and rigid glasses as well. The extensive investigations on the system converge to a general scheme, according to which upon irradiation of the enol tautomer, its electronic excited state is converted to the excited cis-keto form, which subsequently may lead either back to the enol form, or to the final photoproduct, the trans-keto form. It has been shown that photochromism is a characteristic property of the molecules and the chromo-behaviour is influenced by the environment such as the crystal packing of the compounds in the solid state and the nature of the solvent in solution. Anils, apart from their fundamental interest, have potential for applications based on their ability to change some of their properties upon irradiation, when proton transfer between the enol and the keto occurs.

The specific features of intramolecular OH···N hydrogen bonds in o-hydroxyphenyl Schiff bases are discriminated. They are identified as resonance assisted low-barrier hydrogen bonds. The properties of such bridges are best reflected in infra-red absorption spectra and particularly in the stretching OH or NH bands. As shown, the most characteristic is the low intensity of these bands. The discussion is presented for a number of examples represented by the Mannich and Schiff bases, 2-hydroxybenzamides as well as by liquid crystalline o-hydroxyphenyl Schiff bases and ohydroxyazobenzenes. The interaction effects through the bifurcated hydrogen bonds between the chelate rings are distinguished. Based on the quantum mechanical calculations the potential energy curves describing the proton motion are analysed for the isolated molecules and condensed phases showing a high anharmonicity. In the last part of the review the infra- red spectra in the finger print region are analysed from the point of view of tautomeric equilibria related to the proton transfer.