The imidazole (IMZ) ring presents several chemical properties that turns it into a versatile acid-basic/nucleophilic catalyst. The discovery of the biological properties of histidine (amino acid with IMZ ring) instigates the study of this class of compounds. It is found in nature in several enzymes such as chymotrypsin and RNAses due to these properties. This review is focused on the catalytic role of IMZ towards the cleavage of acyl and phosphate esters and is structured in the following topics: chemical properties, biological catalysis (RNAses, phosphohistidines, chymotrypsin), intermolecular and intramolecular catalytic models and polymer and nanomaterials-based catalysts. Besides we discuss some properties such as tautomerism, stability, basicity and spectroscopic behavior, correlating with its reactivity in deacylation and dephosphorylation reactions. The main reaction mechanisms and kinetics promoted by IMZ as an acid, basic and nucleophilic catalysts are explored showing some examples. In addition, the importance of IMZ in enzymatic sites and their mechanisms and further combining properties of IMZ with some materials such as (bio)polymers, graphene, and cyclodextrines are covered. In this sense, with the wide IMZ data presented here, we are evidencing the perfect match between IMZ and catalysis.

Is the broad mechanistic versatility of imidazole towards organophosphates (OPs), that has inspired many catalysts and sensors, beneficial? Herein, a thorough analysis is given seeking to unravel this puzzle. For OPs from the P=O family, imidazole attacks the phosphorus atom exclusively (N-phosphorylates). With the P=S family which are less reactive, an unusual N-alkylation predominates. Surprisingly, imidazole reacts with methyl parathion exclusively at the aliphatic carbon, whilst for the ethylated analogue parathion, imidazole reacts by two pathways: at both the phosphorus and aliphatic carbon, with predominance for the latter. The preference for the electrophilic center can be modulated by the pH. Overall, a mechanistic structure-related trend is observed: imidazole tends to prefer other electrophilic centers than the phosphorus for less reactive OPs. Moreover, this gives important insights concerning the challenging chemistry of imidazole alkylation and the outcomes for monitoring systems that depend on the detection of degradation products. Finally, a thorough comparison with the literature is presented seeking to understand how imidazole reacts towards various OPs. We suggest that the promiscuity of imidazole boosts up its versatility.

Herein, we propose an interdisciplinary experiment for undergraduate course that involves concepts of organic and physical chemistry. Firstly, we propose the synthesis of three nitrophenyl acetates, varying the substituent position. Afterwards, we describe the construction of a homemade colorimeter using inexpensive materials and LED as both emission and detection dispositives. Finally, the colorimeter is used to follow the nucleophilic acyl transfer reactions catalyzed by imidazole under pseudo-first order conditions for the reactions of p-nitrophenyl, o-nitrophenyl and m-nitrophenyl acetate with imidazole. The substituent effect is correlated to the reactivity of the acetates, one of the benchmarks of a physical organic chemical approach. The effect of imidazole concentration is also evaluated. The proposed experiment is interesting because the students can thoroughly understand how a spectrophotometer works and since each student can construct their own colorimeter, they don't have to rely on any equipment infrastructure. Additionally they can correlate two important areas: organic and physical chemistry by using a kinetic study in the understanding of organic reactions. Indeed, physical organic chemistry is a field of increasing interest specially for elucidating mechanisms and introducing students to this interdisciplinary approach is interesting since several undergraduate concepts are covered.