Aromatic compounds in biochemistry

Compounds with aromatic rings occupy numerous and important positions in reactions that occur in living systems. It would be impossible to describe than all in this chapter. We shall, however, point out a few examples now and we shall see others later. 

Two amino acids necessary for protein synthesis contain the benzene ring  

Dairy products, beans, fish, meat, and pouitry are dietary sources of the essentiai amino acids. 

A third aromatic amino acid, tryptophan, contains a benzene ring fused to a pyrrole ring. (This aromatic ring system is called an indole system, see Section 20.1B.) 

It appears that humans, because of the course of evolution, do not have the biochemical ability to synthesize the benzene ring. As a result, phenylalanine and tryptophan derivatives are essential in the human diet. Because tyrosine can be synthesized from phenylalanine in a reaction catalyzed by an enzyme known as phenylalanine hydroxylase, it is not essential in the diet as long as phenylalanine is present. 

---

Fuchs G, MBS Mohame, U Alenschmidt, J Koch, A Lack, R Brackmann, C Lochmeyer, B Oswald (1994) Biochemistry of anaerobic biodegradation of aromatic compounds. In Biochemistry of Microbial Degradation (Ed C Ratledge), pp. 513-553. Kluwer Academic Publishers, Dordrecht, The Netherlands. 

EVANS V7.C. 1977. Biochemistry of the bacterial catabolism of aromatic compounds in anaerobic environments. Nature, London, 270, 17-22. 

Our study of heterocyclic compounds is directed primarily to an understanding of their reactivity and importance in biochemistry and medicine. The synthesis of aromatic heterocycles is not, therefore, a main theme, but it is useful to consider just a few examples to underline the application of reactions we have considered in earlier chapters. From the beginning, we should appreciate that the synthesis of substituted heterocycles is probably not best achieved by carrying out substitution reactions on the simple heterocycle. It is often much easier and more convenient to design the synthesis so that the heterocycle already carries the required substituents, or has easily modified functions. We can consider two main approaches for heterocycle synthesis, here using pyridine and pyrrole as targets. 

Kosan Biosciences was formed almost 6 years ago, founded on an interest in polyketides, microbial metabolite-based drugs. Polyketides have many diverse chemical structures including erythromycin, which will be mentioned again later. These chemicals include fused-ring aromatic compounds, compounds decorated with sugars, and compounds with large stretches of double bonds. Each of these compounds has different biological activities and utilities, but they are all made in nature by very similar biochemistry. 

Sjoblad, R. D., and Bollag, J.-M. (1981). Oxidative coupling of aromatic compounds by enzymes from soil microorganisms. In Soil Biochemistry, Vol. 5, Paul, E. A., and Ladd, J. N., eds., Marcel Dekker, NewYork, 113-125. 

Levine, R.L., Federici, M.M. (1982) Quantitation of Aromatic Residues in Proteins Model Compounds for Second-Derivative Spectroscopy, Biochemistry 21, 2600-2606. 

Proton transfer reactions play very important role in chemistry and biochemistry [1-3]. Considerable attention has been focused on the gas phase reactions in the last decades, since they are free of the solvent pollution thus being related to the intrinsic reactivity [4 6]. In particular, investigations of gas-phase acidities and basicities were some of the major undertakings in the field [7,8]. The proton affinity (PA), on the other hand is an interesting thermodynamic property by itself. It gives useful information on the electronic structure of base in question and serves as an indicator of the electrophilic substitution susceptibility of aromatic compounds [9]. It is the aim of this article to describe some recent advances in theoretical calculations of the proton affinities of substituted aromatics. We shall particularly dwell in more detail on the additivity rules, which enable simple and quick estimates of PAs in heavily substituted benzenes and naphthalenes. Some prospects for future developements will be briefly discussed too. 

Chymotrypsin catalyzes the hydrolysis of peptide bonds adjacent to aromatic amino acid residues in the protein being hydrolyzed other residues are attacked at a lower frequency. In addition, chymotrypsin catalyzes the hydrolysis of esters in model studies in the laboratory. The use of model systems is common in biochemistry because a model provides the essential features of a reaction in a simple form that is easier to work with than the one found in nature. The amide (peptide) bond and the ester bond are similar enough that the enzyme can accept both types of compounds as substrates. Model systems based on the hydrolysis of esters are frequendy used to study the peptide hydrolysis reaction. 

QMs exist in three isomeric forms, namely, o-, m-, and p-quinone methides (also known as o-, m-, and p-QMs) (Figure 7.5). The importance of o- and p-QMs in organic synthesis and their role in biochemistry have been studied in detail. Urdike benzoquinones, o- and p-QM derivatives are highly polarized compounds, usually observed with difficulty or postulated as reactive intermediates because of facile reactions driven by the formation of aromatized phenol derivatives. 

Pullman, A. 1970. The present image of hetero-aromatics in quantum chemistry - revolution or evolution In Quantum aspects of heterocyclic compounds in chemistry and biochemistry. Proceedings of an international symposium held in Jerusalem, 31 March-4 April 1969, ed. E. D. Bergmann and B. PuUman, 9-31. Jemsalem Jerusalem Academic Press. 

N. Kaubisch, J. W. Daly, and D. M. Jerina, Arene oxides as intermediates in the oxidative metabolism of aromatic compounds Isomerization of methyl-substituted arene oxides, Biochemistry 11, 3080-3088 (1972). 

Proton transfer reactions (proton association and dissociation) in the excited state of aromatic compounds are elementary processes in both chemistry and biochemistry. The acid-base properties in the excited state of aromatic compounds are closely related to electronic structure, which is considerably different from that in the ground state. A large number of studies on the acidity constants pK in the excited state of aromatic compounds have shown that the pK values are markedly different from the acidity constants pK in the ground state [1-31]. 

For the studies of the excited-state proton transfer reactions of aromatic compounds, kinetic analyses by means of fluorimetry, single-photon counting, and laser photolysis methods are very important to obtain the exact data. Their acid-base properties in the excited states can be understood on the bases of thermodynamic analyses and electronic structures. Large changes in the acidity constant of organic compounds upon electronic excitation may be applicable to various fields, especially to biochemistry. 

Saturated or alicyclic ring systems actually are of equal if not greater importance in biochemistry than aromatic compounds derived from benzene, which dominate... 

Liquid chromatography/electrochemistry (LCEC) has become recognized as a powerful tool for the trace determination of easily oxidizable and reducible compounds. This is because detection of as little as 0.1 pmol of material is readily accomplished with relatively simple and inexpensive equipment. Initial interest in LCEC was generated by the determination of several aromatic matabolites of tyrosine in the central nervous system. However, the application of LCEC into other areas of biochemistry has begun at a growing pace. A bibliography of LCEC applications is available... 

Wardman P, Dennis MF, Everett SA, Patel KB, Stratford MRL, Tracy M (2003) Radicals from one-electron reduction of nitro compounds, aromatic N-oxides and quinones the kinetic basis for hypoxia-selective, bioreductive drugs. Biochem Soc Symp 61 171-194 Warman JM, de Haas MP, Hummel A, van Lith D, VerberneJB, Loman H (1980) A pulse radiolysis conductivity study of frozen aqueous solutions of DNA. Int J Radiat Biol 38 459-459 Warman JM, de Haas MP, Rupprecht A (1996) DNA a molecular wire Chem Phys Lett 249 319-322 Warters RL, Lyons BW (1992) Variation in radiation-induced formation of DNA double-strand breaks as a function of chromatin structure. Radiat Res 130 309-318 Warters RL, Hofer KG, Harris CR, Smith JM (1977) Radionuclide toxicity in cultured mammalian cells Elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 12 389-407 Weiland B, Huttermann J (1998) Free radicals from X-irradiated, dry and hydrated lyophilized DNA as studies by electron spin resonance spectroscopy analysis of spectral components between 77 K and room temperature. Int J Radiat Biol 74 341-358 Weinfeld M, Soderlind K-JM (1991) 32P-Postlabeling detection of radiation-induced DNA-damage identification and estimation of thymine glycols and phosphoglycolate termini. Biochemistry 30 1091-1097... 

---