We present a novel series of hydrogen-bonded, polycrystalline 1:1 complexes of Schiff base models of the cofactor pyridoxal-5'-phosphate (PLP) with carboxylic acids that mimic the cofactor in a variety of enzyme active sites. These systems contain an intramolecular OHN hydrogen bond characterized by a fast proton tautomerism as well as a strong intermolecular OHN hydrogen bond between the pyridine ring of the cofactor and the carboxylic acid. In particular, the aldenamine and aldimine Schiff bases N-(pyridoxylidene)tolylamine and N-(pyridoxylidene)methylamine, as well as their adducts, were synthesized and studied using 15N CP and 1H NMR techniques under static and/or MAS conditions. The geometries of the hydrogen bonds were obtained from X-ray structures, 1H and 15N chemical shift correlations, secondary H/D isotope effects on the 15N chemical shifts, or directly by measuring the dipolar 2H-15N couplings of static samples of the deuterated compounds. An interesting coupling of the two "functional" OHN hydrogen bonds was observed. When the Schiff base nitrogen atoms of the adducts carry an aliphatic substituent such as in the internal and external aldimines of PLP in the enzymatic environment, protonation of the ring nitrogen shifts the proton in the intramolecular OHN hydrogen bond from the oxygen to the Schiff base nitrogen. This effect, which increases the positive charge on the nitrogen atom, has been discussed as a prerequisite for cofactor activity. This coupled proton transfer does not occur if the Schiff base nitrogen atom carries an aromatic substituent.

Crystal structures of Schiff bases containing pyridoxal (PL), N-(pyridoxylidene)-tolylamine, C(15)H(16)N(2)O(2) (I), N-(pyridoxylidene)-methylamine, C(9)H(12)N(2)O(2) (III), and their 1:1 adduct with 2-nitrobenzoic acid, (I)(+) C(7)H(4)NO_4;- (II), and 4-nitrobenzoic acid, (III)(+) C(7)H(4)NO_4;- (IV), serve as models for the coenzyme pyridoxal-5'-phosphate (PLP) in its PLP-dependent enzymes. These models allow the study of the intramolecular OHN hydrogen bond of PL/PLP Schiff bases and the H-acceptor properties of their pyridine rings. The free base (I) forms hydrogen-bonded chains involving the hydroxyl side groups and the rings of adjacent molecules, whereas (III) forms related hydrogen-bonded cyclic dimers. The adducts (II)/(IV) consist of 1:1 hydrogen-bonded complexes, exhibiting strong intermolecular bonds between the carboxylic groups of the acids and the pyridine rings of (I)/(III). In conclusion, the proton in the intramolecular O-H...N hydrogen bond of (I)/(III) is located close to oxygen (enolamine form). The added acids protonate the pyridine ring in (II)/(IV), but only in the latter case does this protonation lead to a shift of the intramolecular proton towards the nitrogen (ketoimine form). All crystallographic structures were observed in the open form. In contrast, the formation of the pyridinium salt by dissolving (IV) leads to the cyclic aminal form.

The X-ray molecular structure of the important molecule 3,5-bis(triÑuoromethyl)pyrazole has been determined at 120 K and gave crystals belonging to the triclinic space group. The compound forms tetramers through P1 6 NÈHÉ É ÉN hydrogen bonds and some proton disorder is necessary to explain the geometric features of the monomers. The IR spectra have been recorded in the gas phase (monomers) and in the solid state (tetramers) and analyzed by comparison with the calculated normal frequencies. The use of solid-state NMR spectroscopy combined with ab initio GIAO calculations suggests that a certain amount (about 40 ^10%) of dynamic disorder involving intramolecular proton transfers could be present in the crystal.

Results are reported of variable‐temperature 15N cross‐polarization magic angle spinning (CP/MAS) NMR experiments performed on [15N2]‐labelled polycrystalline 3,5‐dibromo‐1H‐1,2,4‐triazole (2b) and 3,5‐dichloro‐1H‐1,2,4‐triazole (3b), the synthesis of which is also described. According to the crystal structures these compounds form cyclic trimers in the solid state. The molecular and hydrogen bond structures were compared with those derived from ab initio calculations. The 15N CP/MAS NMR spectra show temperature‐dependent lineshapes which were analysed in terms of near‐degenerate triple proton transfer processes. The equilibrium constants are slightly different from unity as observed by high‐temperature line splittings. The populations of the two quasi‐degenerate tautomers were calculated from the internal angles at N1 and N2 and compared with those obtained from solid‐state NMR; both methods agree fairly well. By lineshape analysis rate constants of the triple proton transfer processes were obtained at different temperatures. The proton transfer kinetics of 2b and 3b were compared with those of 3,5‐dimethylpyrazole, 4‐nitropyrazole and 4‐bromopyrazole, studied previously, which also form cyclic trimers in the solid state, exhibiting more or less concerted, degenerate triple proton transfer processes proceeding by tunnelling at low temperatures. It is shown that the triazoles behave in a similar way to the pyrazoles. The barrier heights of the triple proton transfer increase monotonically with the distance between the two nitrogen atoms involved in the proton transfer. It is shown that the intrinsic nitrogen chemical shifts are related to the N...H distances. Copyright © 2000 John Wiley & Sons, Ltd.