Carbon-centered radicals cations

Racemization of chiral centers often involves a planar intermediate reaction center (e.g., carbon-centered radical, cation, or anion) where the reacting molecule can approach the reaction center either from one side of the planar surface or the other side resulting in either partial or complete racemization of the chiral center. 

Research on carbon-centered radical cations in solution accelerated dramatically with the development of time-resolved optical absorption and emission techniques. The research group of Th. Forster in Germany pioneered photochemical methods of production of radical cations and anions, as well as exciplexes." While the Forster group focused on structure and lifetimes, the later work of D. R. Arnold in Canada, and of H. D. Roth in the United States," reported the reactivity of photochemically generated radical cations from a mechanistic perspective. These studies of radical ion chemistry evolved into the field we now know as electron donor-acceptor interactions, arich area of science in which carbon-centered radical cations are stiU actively smdied. 

Abstract Diazonium salts have been previously used to cleave DNA via generation of carbon centered radicals and cations. Efforts have been made in the past decade or so to develop diazo compounds and a-diazoketones for physiologically relevant DNA cleavage. These efforts, coupled with their relevance to the mechanism of action of kinamycin and lomaiviticin antibiotics and other naturally occurring diazo compounds, will be discussed. 

Similar to the intramolecular addition of neutral carbon-centered radicals to alkenes, the formation of radical cations starting from alkenes with subsequent cyclization offers a convenient method for constructing carbocyclic ring systems. In contrast to the regioselective 1,5-ring closure (5-cxo-trig cyclization) of the... 

Photoinduced single-electron transfer followed by fragmentation of the radical cation is an efficient method for generating carbon-centered radicals under exceptionally mild conditions. The fate of the thus formed radicals depends primarily on their interaction with the acceptor radical anions. Typically observed reactions are either back-electron transfer or radical coupling, but from the synthetic point of view, another most intriguing possibility is the trapping of the radical with suitable substrates such as olefins (Scheme 16). 

In the latter case, the aminomethylene radical is formed upon deprotonation of the cation radical. Unless proton equilibrium for one of these two radical types is much slower than for the other type, the radical that corresponds to the lowest pKa should be formed upon deprotonation of the cation radical (Et2NH)+. This cation radical has pKa = 5.3 in aqueous solutions at pH 3-9. Therefore, 02 saturation of the solutions does not affect the determined pKa (Jonsson et al. 1996). Since 02 reacts more rapidly with carbon-centered radicals than with nitrogen-centered radicals, one can conclude that deprotonation of (Et2NH)+ takes place at the nitrogen rather than at the a-carbon. 

In the case of amines, protonation that withdraws electron density from the center of reaction lowers the rate of reaction by a factor of 30 (Das and von Sonntag 1986). Besides H-abstraction from carbon [reactions (18) and (21)], the formation of N-centered radical cations is observed [reactions (19)/(22) and (20) for amino acids see, e.g Bonifacic et al. 1998 Hobel and von Sonntag 1998]. Reaction (20) is also an H-abstraction reaction. The ET reaction (19)/(22) may proceed via a (bona-fide, very short-lived) adduct (Chap. 7). 

In summary, trapping methodology helped to confirm the presence of the three main NMMO-derived radical species, the nitrogen-centered radical cation 3 and the carbon-centered radicals 4 and 5 in Lyocell dopes. Trapping... 

The mechanism of melatonin s interaction with reactive species probably involves donation of an electron to form the melatoninyl cation radical or through a radical addition at the site C3. Other possibilities include hydrogen donation from the nitrogen atom or substitution at position C2, C4, and C7 and nitrosation [169]. The mechanisms by which melatonin protects against LP most likely involve direct or indirect antioxidant and free-radical scavenging activities of this indoleamine [169,171]. 2-Phenyl indole derivatives have redox properties because of the presence of an electron-rich aromatic ring system that allows the indoleamine to easily function as an electron donor. For these derivatives, the possible antioxidant mechanism might be most probably toward carbon-centered radicals described by Antosiewicz et al. [172]. 

The unstable aryl cation radical undergoes Ca-C cleavage to form the benzaldehyde (2) and a C6C2 benzyllc radical Intermediate. EPR evidence for such carbon-centered radical Intermediates In LIP oxidation has also been presented (55). The benzyllc radical Intermediate Is attacked preferentially by O2 under aerobic conditions and the resulting hydroperoxy radical would decompose to form the phenylglycol (3)... 

The first one electron oxidation produces a radical cation on the sugar phosphate (SP +). The radical cation subsequently deprotonates yielding a neutral carbon centered radical SP(-H). The second oxidation involves an electron transfer from SP(-H) to a nearby guanine radical cation G +. This step requires that the hole on the guanine have some mobility. It is known that a hole located on guanine at 4K is mobile, with a range of ca. 10 base pairs [76], The result of this second oxidation is a a deoxyribose carbocation SP(-H)+. 

In either event, the decrease in the metal d orbital energy expected to accompany such metal-centered oxidations would limit the metal contribution to the HOMO in the resulting dication [107]2+, which would be anticipated to display considerable carbon character. Indeed, the third oxidation of 107 gives the open-shell cation [107]3+, for which experimental evidence strongly supports a predominantly carbon-centered radical... 

Upon photolysis, pyridinium salts undetgo cleavage of the carbon-nitrogen bond to form pyridinium radical cation and alkoxy radical. The nitrogen centered radical cations were spectroscopically detected by laser flash photolysis... 

Pulse radiolysis studies using optical detection suggested the main species in equilibrium to be the ot-aminoalkyl radical (31) and the A -protonated ot-aminoalkyl radical (32) whereas results from ESR studies were indicative of protonation at the a-carbon site to form the iV-centered radical cation (30). A subsequent study showed that these results could be attributed to kinetic and thermodynamic factors [84]. Thus iV-protonation resulting in the formation of 32 is kinetically favored and is hence observed in the short time-scales involved in pulse-radiolysis systems. In the longer times involved in ESR measurements the thermodynamically more stable N-centered radical cation will be observed. The pA a of 30 and 32 were estimated as 8.0 and 3.6 by use of pulse radiolysis [84]. Using the equation for similar keto enol tautomerism of barbituric acid [97], the ratio of 30/32 was estimated to be 10 /10 = 10", indicating the N-centered radical (30) to be the predominant protonated species. 

An explanation can be found in terms of the much lower reduction potential of the indole-type radical cations as compared to the phenylalkanoic acid ones, which results in a greater stabilization of the positive charge on the aromatic system thus opposing intramolecular electron transfer. In other words, a later transition state is expected in the decarboxylation of indole-type radical zwitterions as compared to the phenylalkanoic acid ones, with an increased importance of the stability of the carbon centered radical. 

Aminocyclopropane derivatives are known to possess enzyme inhibitory properties.In particular, aminocyclopropanes are potent inhibitors of cytochrome P-450 mono-oxygenases. A carbon-centered free radical, generated by one-electron oxidation of aminocyclopropane by P-450 to form a nitrogen-centered radical cation and subsequent ring opening, may play an important role in the destruction of the enzyme. 

Electrochemical oxidation of A-CBA supports this hypothesis (95). These data indicate that the oxidation potential of A-CBA is within the capabilities of a flavoenzyme, and a similar partition ratio is observed in the oxidation of the benzylmethylene carbon versus the A-cyclopropyl carbon. This preliminary mechanism is thus consistent with the two one-electron transfer process and the nitrogen-centered radical cation proposed for the oxidation of normal substrates by MAO (Scheme 17). 

Fragmentation of the C-M bonds of Group 4A organometallic radical-cations usually generates carbon-centered radicals which add to the reduced form of the acceptor to give coupling products [21] (Scheme 11). 

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