The synthesis and characterization of 5,10,15,20-tetrakis(2,6-dimethyl-3-sulfonatophenyl)porphyrin (3) and its iron(III) complex (3-Fem) are described. Both 3 and 3-Fem hydrate exist as a mixture of atropisomers due to the dissymmetry of the four 2,6-dimethyl-3-sulfonatophenyl substituents. Spectrophotometric titrations of the atropisomer mixture at a number of wavelengths establish that the observed changes in absorbance with change in pH fit (±0.05 and ±0.08 pH units) to the equation for the titration of a single monobasic acid (3-Fem(H20)2 3-Fe,n(H20)(0H) + H+; pKa = 7.25). Ligation of a second hydroxyl group (i.e., 3-Fem(H20)(0H) ¡=t 3-Fem(HO)2 + H+) is not seen on titration to pH 14. The observation of a single pK¡ shows that the various atropisomers possess the same acidity. Therefore, oxyligands attached to the iron(III) moiety of the various atropisomers are under the same electronic influence. The same conclusion is reached from electrochemical measurements. The water-soluble aquo-ligated 3-Fem does not show spectral evidence for self-association nor µ-dimer

The pH dependence of the mechanism of reaction of hydrogen peroxide with a nonaggregating, non-,R-oxo dimer-forming iron(HI) porphyrin in water ( Contributed by Thomas C. Bruice, March 3, 1986 ABSTRACT The reaction of hydrogen peroxide with 5, 10,15,20-tetrakis(2,6-dimethyl-3-sulfonatophenyl)porphinatoiron(Il) hydrate [(P)Fem(H20)] has been investigated in water between pH 1 and pH 12. The water-soluble (P)Fe"'(H20) neither aggregates nor forms a ,.-oxo dimer. The pH dependence and rate-limiting second-order rate constants (k1y) for oxygen transfer from H202 and H02 to the iron(III) porphyrin were determined by trapping of the resultant higher-valent iron-ox~o porphyrin species with 2,2'-azinodi(3-ethylbenzthiazoline)-6-sulfonate (ABTS). Reactions were monitored spectrophometrically by following the'appearance of the radical ABTS-+. From a plot of the logarithm of the determined second-order rate constants for reaction of hydrogen peroxide with iron(EI) porphyrin vs. pH, the composition of the

In order to study the orientation and distance dependence of TC-TI interactions between flavins in various redox states, two approaches to bis(isoal1oxazine) model compounds are presented: The [3.3]isoalloxazinophanes 2 and 4 and the rigid single-bridged 1,8-naphthalene-and l$-anthracene-linked bis(isoal1oxazine) systems 6, 8 and 26 were synthesized, characterized, and studied by spectroscopic methods and cyclic voltammetry. The experimental data are discussed in comparison with "monomeric" isoalloxazines and flexible singlechain trimethylene-linked bis(isoal1oxazine) reference compounds. X-Ray structure analyses are reported for the 1,8-bis(isoalloxazinyl)-9,1O-dihydroanthracene 26 and for 22 as an example of 1,8-disubstituted naphthalenes with strongly polar substituents comparable to 6.One of the most important features in flavin chemistry is the ability of the isoalloxazine system to exist in three different stable redox states: the flavoquinone, the flavoseniiquinone radical and the flavohydroquinone. These redox states can be further modified by protonation or deprotonation, formation of hydrogen bonds or steric factors. For these reasons, the flavocoenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) play an essential role in biological processes as mediators between nicotinamide nucleotides as exclusive two-electron carriers and typical oneelectron carriers such as ferredoxin iron sulfur clusters or metalloporphyrins. It has also been postulated that in the active site of some enzymes (e. g. NADPH-cytochrome P4,,-reductase) two flavins act as a single redox-active unit [*].The quinhydrone-like association of oxidized and reduced flavins was first discussed by Kuhn and Strobele[31. Although the spectroscopic properties of semireduced flavin systems have been studied extensively since thenr41, the spatial arrangement favoring chargetransfer interactions and the exchange of redox equivalents by electron transfer is still a matter of controversial discussionc51. In the past, there have been some attempts to inimic these interactions by open-chain trimethylene-linked bis(isoalloxazines)[61. As a major disadvantage of such models, however, it must be realized that their steric structure due to the flexibility of the linking chain is not welldefined. Suitable model systems for determining the orientation and distance dependence of flavin-flavin interactions require clearly defined rigid geometries with sandwich-like flavin-flavin orientation as well as a controlled variation of interplanar distances by the choice of different spacer groups.With the intention to contribute to the understanding of flavin coenzyme functions we tried to synthesize models meeting these requirements. Results referring to flavin-flavin interactions are described in this paper; in the following papers we report on an analogous approach in the attempt to synthesize models for flavin interactions with nicotinamidec7I and quinones[*].Based on earlier extensive experiences of our group in using the "cyclophane concept...

Nicotinic ester and nicotinic acid isoalloxazinophanes, intramolecular interactions of, X-ray structure analyses of / Flavin-nicotinamide models As model systems for active site complexes i n flavoenzymes, lato derivatives (2 and 34, resp.), of 4 by multistep syntheses. flavin and nicotinamide analogues were linked together in For the isoalloxazinophanes 2, 3, 4, and 34 X-ray structure cyclophane skeletons of specific sterical structures. Elaborat-analyses were performed and are discussed with regard to ing this concept, w e prepared [4]metacyclo[3]( 10,6)isoalloxa-intramolecular interactions. Preliminary UV/Vis-spectrozinophane (3), [4](3,l)pyridino[3]( 10,6)isoalloxazinophane scopic results related to r . .~ interactions in these isoalloxazi-(4), as well as the 16-methoxycarbonyl and the 16-carboxy-nophanes are reported.The important role flavins play "at the crossroad of biological redox chemistry"[*] is directly related to the fact that flavins represent a versatile system of various redox states and are capable of transferring one-electron as well as two-electron equivalents. As a consequence of these specific properties, flavin coenzymes -flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD) -often act in enzymatic reactions as mediators between otherwise incompatible redox systems. For example, FAD in glutathione reductase catalyzes the two-electron reduction of oxidized glutathione by dihydronicotinamide-adenine dinucleotide phosphate (NADPH). The X-ray structure analysis of glutathione reducta~e [~] and the subsequent investigation of mechanistic details of this enzyme as well as of the geometry of its active stimulated further interest with regard to interactions between flavin and nicotinamide units.Open-chain trimethylene-linked flavin-nicotinamide systems were synthesized already in the mid-70s, and charge-transfer interactions between flavin and nicotinamide in their respective reduced and oxidized states wereThe high flexibility of these open-chain models, however, did not allow the observed effects to be ascribed precisely to specific mutual orientations of the interacting units.In order to limit the conformational diversity we tried to obtain less flexible systems by a twofold bridging from the 5-and 6-positions of nicotinamide to the 6-and 9-positions of the isoalloxazine unit by tetramethylene chainst61. Whereas these attempts, due to synthetic difficulties, were not successful yet, we report in this paper on syntheses and properties of nicotinamide-flavin models in which the interacting components are kept in a rigid face-to-face orientation by a suitable cyclophane skeleton. The "cyclophane concept" had been successfully used, for example, for studying the redox equivalent exchange between two nicotinic ester units of different redox statesr71, for investigating flavin-flavin interactions ['], and more generally for studying charge-transfer[*] and ex~imer [~] interactions as well as, rather recently, photoinduced electron-transfer reactions in porphyrin-quinone cyclophanes~'Ol....

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