Heterolytic and Homolytic Y-NO Bond Energy Scales of Nitroso-Containing Compounds: Chemical Origin of NO Release and NO Capture Jin-Pei Cheng,* ,† Ming Xian, † Kun Wang, † Xiaoqing Zhu, † Zheng Yin, † and Peng George Wang* ,‡ Departments of Chemistry Nankai UniVersity, Tianjin 300071, China Wayne State UniVersity, Detroit, Michigan 48202 ReceiVed June 16, 1998 Nitric oxide (NO), known today as the simplest intra- and intercellular signaling molecule, plays key roles in regulating many important physiological functions in living bodies. 1-5 To understand logically and maybe even quantitatively the chemical origins of NO’s physiological roles, detailed information regarding quantitative energetic changes in NO-related bonding during its biological transformations has to be disclosed at a molecular level. Since NO is such a small diatomic molecule and is expected not to be too strongly affected by steric or molecule shape-dependent recognition factors that large molecules often encounter, the binding force of NO with a particular active site can therefore be represented by the bond energy of the Y-NO type, where Y is the atom to which NO is actually attached. Here we report the establishment of the first such Y-NO bond energy scale by direct calorimetric measurements combined with relevant electrochemi- cal data for three types of N-nitroso compounds, to facilitate the understanding of the driving force for NO release and capture. Although the NO + binding energies for many small neutral organic molecules in the gas phase (also called NO + affinities) have been determined by using ion cyclotron resonance spec- trometry, 6,7 Y-NO bond energy, where Y is a relatively large organic moiety, is virtually absent from all thermodynamic data bank, 8 because Y is very apt to undergo secondary bond cleavages during the gas-phase bond energy measurement, making the separation of the heats from the primary process essentially impossible. However, the recent development in the bond energy determination utilizing the easily accessible solution thermody- namic quantities 9-15 implies that the problems encountered in the gas phase should no longer be a primary obstacle in solution, as long as the anion (Y - ) and nitrosonium cation can be successfully manipulated in a single solvent at the same time. The thermo- dynamic cycle in this work to derive the desired Y-NO bonding information is based on Arnett’s 9 and Bordwell’s 10 work, in which they have shown that the difference between heterolytic bond energy (ΔH het ) and homolytic bond energy (ΔH homo ) is the enthalpy of electron transfer, which is approximated closely by the free energy of electron transfer (ΔG ET ). 16 Thus, ΔH het of Y-NO can be obtained from the heat of combination reaction between Y - and NO + , and ΔH homo from ΔH het in combination with the reduction potential (E red ) of NO + and the oxidation potential (E ox ) of Y - (Scheme 1). Similar approaches were successfully applied recently for deriving C-H bond energies 11 and C c -C a (where C c and C a represent resonance-stabilized carbocations and carbanions, respectively) bond energies. 9 Three types of N-nitroso compounds, including N-nitrosoureas (1), N-nitrososulfonamides (2), and N-nitrosophosphoramides (3) (Chart 1), were chosen in this work for measurement of Y-NO bond energies. The success of the heat measurement largely depends on two key factors: (i) the combination reactions of NO + with anions have to be a quantitative reaction without any side reaction and (ii) the solvent used should be stable to both the strongly electrophilic nitrosonium cation and the strongly basic anion of interest during the entire titration experiment. We found that the chosen reaction systems of this work in acetonitrile met all the criteria for both calorimetric and electrochemical measure- ments. The cleanness of the combination reactions under calorimetric conditions was confirmed by comparison of the product with the authentic samples specially prepared. The nitrogen anion was generated through the reaction of the parent aniline with potassium hydride. Nitrosonium perchlorate (NO + - ClO 4 - ) served as NO + source. The titration experiment was carried out under argon in dry acetonitrile solution at 25 °C using a Tronac 458 calorimeter. After a certain amount of NO + solution in MeCN (usually 25 mM in concentration) was titrated through a carefully calibrated motor-driven buret to the reaction vessel containing an excess amount of the nitranion of interest, the heat generation was computer-processed to give the heat of the reaction (ΔH rxn ), 9 which can be easily converted to the heat of heterolysis (ΔH het ) by switching the sign. The cyclic voltammograms were obtained on a BAS 100B electrochemical analyzer equipped with a three-electrode analytical cell at a sweep rate of 100 mV/s in dried and degassed 0.1 M Bu 4 NPF 6 -MeCN under argon. The ΔH het s and ΔH homo s of 1-3 and the electrochemical data necessary for the evaluations are presented in Table 1. The pK a 14 and bond dissociation energy (BDEs) 15 of the Y-H parent molecules determined here are listed (whichever available) for comparison. The data in Table 1 show that both N-nitrosoureas and N-nitrosophosphoramides have ΔH het of 50-62 kcal/mol, while N-nitrososulfonamides have considerable lower ΔH het (about 25- 35 kcal/mol). The ΔH het correlates linearly with pK a of the parent compound (Figure 1), indicating that the linear free energy relationship holds in these systems. 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Soc. 1998, 120, 10266-10267 S0002-7863(98)02086-1 CCC: $15.00 © 1998 American Chemical Society Published on Web 09/19/1998