ROLE OF CHARGE‐TRANSFER INTERACTIONS IN FLAVOPROTEIN CATALYSIS

The last decade has produced a veritable explosion of knowledge on the chemical reactivity of the isoalloxazine ring system of the flavin coenzymes, largely because of a side-by-side development with knowledge of flavoenzymes and model flavin studies. In this period the visible absorption spectra and epr spectra of the flavin semiquinone in its cationic, neutral, and anionic forms have been defined'-" (FIGURE 1 ) . In the same period a large number of flavoenzymes have been investigated by rapid reaction spectrophotometric techniques, and in nearly all cases distinctive spectra characterized by longwavelength-absorption bands have been detected as catalytic intermediates. With few exceptions, the spectra of the intermediates are unequivocally different from those of flavin semiquinone in either its neutral or its anionic form. As will be discussed in more detail below, these intermediates are in general readily thought to contain the flavin in the oxidized or reduced state, on the basis of their spectral properties. During this period the great chemical reactivity of the flavin system has been uncovered.',8 This model work has led to the synthesis of well-defined substituted isoalloxazines, with substituents at almost every atom of the isoalloxazine ring system. The recognition of this great reactivity has led to the obvious suggestion that intermediates in flavoenzyme catalysis involve covalent linkage of substrate moieties with the flavin.'-'l While the formation of such intermediates cannot be excluded rigorously on the basis of present evidence, the known spectral properties of such model substituted flavins fail to account for the intermediates observed in flavoenzyme catalysis.