The Electrophilic Reactions of Bound NO

The electrophilic reactions of the nitrosyl ligand constitute one of its most important reactivity modes (12,13,25). This has been known for a long time, and comprehensive reviews are available (28). A general way of describing the course of the reactions of NP with different nucleophiles is through Eqs. (5) and (6)  

With the exception of B = OH-, which relates in fact to an acid-base reaction, the other nucleophiles are potential reductants. After forming the reversible adducts [Eq. (5)], redox reactions are usually operative, leading to the reduction of nitrosyl and oxidation of the nucleophile in Eq. (6). Nevertheless, we will consider first the reaction with B = OH- for the sake of simplicity, and also because it allows for some generalizations to be made on the factors that influence the electrophilic reactivities of different nitrosyl complexes (51). We continue with new results for some N-binding nucleophiles (62,67), which throw light on the mecanisms of N20/N2 production and release from the iron centers. A description of the state of the art studies on the reactions with thiolate reactants as nucleophiles will be presented later. 

Reactivity of Nitrosyl Complexes with OH-The reaction scheme can be described as  

The rate law for NP and other nitrosyl complexes approaches a first order behavior in each reactant for most of the studied systems, affording high values of K,q = K7 x Kg, and sufficiently high concentrations of OH- (55,68). The final product has been clearly identified as [FeII(CN)5N02]4-- No direct spectroscopic evidence on the intermediacy of [FeII(CN)5N02H]3- has been obtained, although kinetic evidence has been provided (55b). A mechanistic interpretation consistent with the value of the second order rate constant and 

In spite of the abundant work on this type of reactivity, no rate constants for the addition reactions had been obtained, with the exception of the [M(CN)5NO]2 ions (M = Fe,Ru,Os) (55,68), until the recently published kinetic measurements for a representative set of nitrosyl complexes MX5NO (M = mainly ruthenium) (51). Table III 

Selected Distances (A), Angles (Degrees), and IR Stretching Frequencies (v, cm ) Calculated for the Different Steps of Reaction 1, at the B3LYP/ 

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The reductive NO chemistry will cover some new developments on the electrophilic reactions of bound nitrosyl with different nucleophiles, particularly the nitrogen hydrides (hydrazine, hydroxylamine, ammonia, azide) and trioxodinitrate, along with new density functional theoretical (DFT) calculations which have allowed to better understand the detailed mechanistic features of these long-studied addition reactions, including the one with OH-. The redox chemistry of other molecules relevant to biochemistry, such as O2, H2O2 and the thiolates (SR-) will also be presented. 

Good linear plots of the pseudo-first order rate constant for the formation of Cyt from Cyt as a function of [OH ] have been found, supporting the above mechanism. Although no evidence for the N-bound nitrous acid intermediate complex was found, the /jqh values derived from the slopes, together with the redox potentials for nitrosyl reduction in the heme compounds are in fair agreement with the general behavior observed for the electrophilic reactions of other nitrosyl complexes, including NP (see below) (51). 

On leather, reactive dyes attach to the amino group of lysine and hydroxyly-sine moieties of collagen. A tanning effect may occur if one reactive group reacts with leather. However, the reaction of the electrophilic group of reactive dyes with water (hydrolysis) competes with the fixation reaction of forming a covalent bond between the dye and the substrate. The hydrolyzed dye cannot react with the fiber. Leather absorbs the noncovalently bound dye like a conventional anionic dye. Unlike on textiles, these hydrolyzed dyes cannot be easily washed off. That is the reason why sometimes no decisive wetfastness improvement can be achieved. 

One example was reported by Tolman and coworkers (78) who found that the copper(I) complex C Tp112 (TpR2=tris(3-(R2)-5-methylpyrazol-l-yl)hydroborate) promotes NO disproportionation via a weakly bound CuITpR2(NO) intermediate (formally a MNO 11 species). The products are N20 and a copper(II) nitrito complex (Eq. (36)). The rate law established the reaction to be first-order in copper complex concentration and second-order in [NO], and this was interpreted in terms of establishment of a pre-equilibrium between NO and the Cu(I) precursor and the Cux(NO) adduct, followed by rate-limiting electrophilic attack of a second NO molecule (mechanism B of Scheme 5) (78b). 

Despite intense study of the chemical reactivity of the inorganic NO donor SNP with a number of electrophiles and nucleophiles (in particular thiols), the mechanism of NO release from this drug also remains incompletely understood. In biological systems, both enzymatic and non-enzymatic pathways appear to be involved [28]. Nitric oxide release is thought to be preceded by a one-electron reduction step followed by release of cyanide, and an inner-sphere charge transfer reaction between the ni-trosonium ion (NO+) and the ferrous iron (Fe2+). Upon addition of SNP to tissues, formation of iron nitrosyl complexes, which are in equilibrium with S-nitrosothiols, has been observed. A membrane-bound enzyme may be involved in the generation of NO from SNP in vascular tissue [35], but the exact nature of this reducing activity is unknown. 

Note that the reaction at the phosphorus atom is postulated to occur by an SN2 (no intermediate formed) rather than by an addition mechanism such as we encountered with carboxylic acid derivatives (Kirby and Warren, 1967). As we learned in Section 13.2, for attack at a saturated carbon atom, OH- is a better nucleophile than H20 by about a factor of 104 (Table 13.2). Toward phosphorus, which is a harder electrophilic center (see Box 13.1), however, the relative nucleophilicity increases dramatically. For triphenyl phosphate, for example, OH- is about 108 times stronger than H20 as a nucleophile (Barnard et al., 1961). Note that in the case of triphenyl phosphate, no substitution may occur at the carbon bound to the oxygen of the alcohol moiety, and therefore, neutral hydrolysis is much less important as compared to the other cases (see /NB values in Table 13.12). Consequently, the base-catalyzed reaction generally occurs at the phosphorus atom leading to the dissociation of the alcohol moiety that is the best leaving group (P-0 cleavage), as is illustrated by the reaction of parathion with OH ... 

When the cation remains coordinated to the nucleophile, the reaction is under association control. Association-controlled reactions are usually slow, because the substrate is not activated and the nucleophile is deactivated. This general class can be subdivided into two groups. In the first (which occurs in the C-alkylation of enolates), the metal is not directly bound to the reactive site. If the transition state is acyclic, conjugate additions will dominate because there is no electrophilic assistance. If it is cyclic, chelation favors addition to the carbonyl ... 

The reaction is association controlled. This implies that there is no electrophilic assistance and the incoming enolate simply behaves as an ion pair. The cation remains bound to the enolate because (a) its basicity is increased by the presence of the methoxy group (the HOMO energy of a simple enolate is a + 0.682/ , whereas its methoxy substituted derivative is a + 0.564/ ), and (b) the presence of the phenyl group lowers the basicty of the benzaldehyde.56 The cryptand accelerates the reaction because it activates the enolate without deactivating the carbonyl functionality. 

Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki reactions employing poly(ethylene glycol) (PEG)-bound aryl halides and sulfonates in palladium-catalyzed cross couplings [71]. It was shown that no additional phase-transfer catalyst (PTC) was needed when the PEG-bound electrophiles were coupled with aryl boronic acids in water under microwave irradiation conditions, in sealed vessels, in a domestic microwave oven (Scheme 16.49). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with ether. 

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