Substituted Pyridinyl Radicals in Aqueous Solutions
(17)S. W. Benson and H. EL O’Neal, Nat. Stand. Ref. Data Ser., Nat. Bur. Stand., No. 21 (1970). (18)R. J. Cvetanovic, Prop. React. Kinet., 2,39 (1964). (19)D. C. Tardy, ht. ,J. 6hem. Kinet., 6,291 (1974). (20)W. M. Jackson and J . R. McNesby, J. Chem. Phys., 36,2272(1962). (21)A. S. Gordon and J. R. McNesby, J. Chem. Phys., 33, 1882 (1960). (22)D.C. Tardy and 8.S. Rabinovitch.J. Chem. Phys., 48,5194(1968). (23)S. P. Pavlou and B. S. Rabinovitch, J. Phys. Chem., 75,3037 (1971). (24)Y. N. Lin and B. S. Rabinovitch, J. Phys. Chem., 74,3151 (1968). (25)W. P. L. Carter and D. C. Tardy, J. Phys. Chem., 78, 1579 (1974). (26)F. D.Rossinii, “Selected Values of Physicaland Thermodynamic Properties of Hydrocarbons and Related Compounds,” Carnagie Press, Pittsburgh, Pa., 1953. (27)C. W. Larson and 9. S. Rabinovitch, J. Chem. Phys., 50,871 (1969). (28)D. M. Golden and S.W. Benson, Chem. Rev., 69,125 (1969). (29)J. A . Dominguez and A. F. Trotman-Dickenson, J. Chem. SOC., 940
(1962). (30)R. J. CvetanlDvic and R. .S. Irwin. J. Chem. Phys., 46,1694 (1967). (31)R. R. Getty, J. A. Kerr, and A. F. Trotman-Dickenson, J. Chem. SOC.A, 979 (1967). (32)C. W~.Larson, B. S. Rabinovitch, and D C. Tardy, J. Chem. Phys., 47, 4570 (1967) (33)E. B. Wilson, J C. Decius, and P C. Cross, “Molecular Vibrations,” McGraw-Hill, New York, N Y., 1955. (34)J. H. Schachtschnider and R. 6. Snyder, Spectrochim. Acta, 19, 117 (1963). (35)N. Neto, C.C)iLauro, E. Castellucci, and S. Caiifano, Spectrochim. Acta, Sect A, 23, 1763 (1967);N. Neto, 6.DiLauro, and S. Califano, ibid., 26,1489 (1970)
221 1 (36)W. P. L. Carter and D. C. Tardy, J. Phys. Chem., submitted for pubiication.
(37)H. S. Johnston, “Gas Phase Reaction Rate Theory,” Ronald Press, New York, N.Y., 1966,pp 80-83. (38)D. C. Tardy and B. S. Rabinovitch, J. Chem. Phys,,,45, 3720 (1966). (39)J. 0.Hirschfelder, C. F. Curtis, and R. B. Bird, Molecular Theory of Gases and Liquids,” Wiley, New York, N.Y., 1954. (40)F. J. Fletcher, 8. S. Rabinovitch, K. W. Watkins, and D.J. Locker, J. Phys. Chem., 70,2823 (1966). (41)Y. N. Lin, S. C. Chan, and B. S. Rabinovitch, J. Phys. Chem., 72, 1932 (1968). (42)M. G.Borisov and L. M. Sverdlov, Opt. Spectrosc., 19,33 (1965). (43)J. E. Kilpatrick and K. S. Pitzer, J. Res. Nat. Bur. Stand., 38, 191 (1947). (44)F. H. Dorer and 6.S. Rabinovitch, J. Phys. Chem., 69,1952 (1965). (45)L. M. Sverdlov and N. V. Tarsova, Opt. Spectrosc., 9,159 (1960). (46)R. G. Snyder and J. H. Schachtschnider, Spectrochim. Acfa, 21, 169 (1965). (47)W. C. Bentrude, Annu. Rev. Phys. Chem., 18, 283 (1967). (48)R. D. McLachlan, Spectrochim. Acta, 23,3793(1967). (49)R., D. McLachlan and R. A. Nyquist, Spectrochim. Acta, Sect A, 24, 103 (1968). (50)L. M.Sverdlov and G. M.Borisov, Opt. Spectrosc., 9,227 (1960). (51)G. Herzberg, “Infrared and Raman Spectra of Polyatomic Molecules,” Van Nostrand, Princeton, N.J., 1945. (52)W. P. L. Carter, Ph.D. Thesis, University of Iowa, Iowa City, iowa, 1973. (53)P. J. Robinson and K. A. Holbrook, “Unimolecular Reactions,” Wiiey-lnterscience, London, 1972. (54)13. F. Eggers, L. W. Gregory, G. D. Halsey, and 5. S. Rabinovitch, “Physical Chemistry,” Wiley, New York, N.Y., 1964,p 373.
Substituted Pyridinyl Radicals in Aqueous Solutions. Formation, Reactivity, and Acid-Base P. Neta” and L. K. Patterson Radiation Research Laboratories and Center for Special Studies, Mellon Institute of Science, Carnegie-Mellon University, Pittsburgh, Pennsy/v.mia 15213 (Received May 6, 1974) P ~ ~ l i c a t i costs o n assisted by Carnegie Mellon Universityand the U,S. Atomic Energy Commission
Pyridinyl radicals have been produced from various pyridines as well as pyridinium cations by reduction with eaq- and, where reactivity allows, by electron transfer. Both meta- and para-substituted carboxy and carbamoyl compounds were investigated. These radicals all exhibit a strong optical absorption band in the region of 300 nm ( e 4000-13,000 A4-l cm-l) and another moderately intense band ( E 2000-7000 M - l cm-l) a t about 400 nm. In all cases the separation between bands was greater for meta radicals than for their para counterlparts. Radical-radical reaction rate constants were measured by monitoring transient decay. Dissociation constants for these intermediates were determined from pH dependent alterations in transient spectra. Two dissociation constants were observed for the carboxypyridinyl radicals (pK1 0; pK2 6) and one for the carbamoyl substituted radicals (pK = 1.3-2.1). It was found that pyridinyl radical disproportionation is enhanced by increased degrees of protonation. Previously reported increase in radical reactivity with decreasing pH may be fully explained by this effect. Comparisons of electron transfer and disproportionation rate constants reveal greater stability for para-substituted pyridinyl radicals than for their meta counterparts. This stability may be due largely to increased conjugation between the ring and para substituent as compared with the meta analog. Results of INDO calculations involving the carboxypyridinyl radicals support this view.
-
Introduction One-electron reduction of pyridines yields pyridinyl radicals. Possible participation of such radicals in biochemical redox reaction involving NAD (nicotinamide adenine dinucleotide) has !$timulated considerable interest in these species. Optical spectra of radicals generated in aqueous
-
solution from reduction of NAD+, nicotinamide, and related pyridines have been measured by pulse radiolysis; associated kinetics of growth and decay have also been examined.2,3Further, an esr study of in situ irradiated solutions has shown that one-electron reduction of pyridine and its carboxy derivatives is followed by rapid protonation on the ring nitrogen even at very high pH.* The Journal of Physical Chemistry, Voi. 78. No. 22, 7976
P. Neta and L. K. Patterson
2212
In aqueous solutions these radicals disappear by secondorder processes. By contrast, however, several derivative radicals such as N - ethyl-4-carbethoxypyridinylhave been prepared in certain organic solvents and found to be stable.5 This pronounced solvent related difference in radical stability has been interpreted in terms of polarity effects on an equilibrium between the radicals and ionic intermediates produced from their disproportionation.6 The effect o f pW an pyridinyl radical decay rates in aqueous solution has been explained 1 n terms of such an equilibrium. In the present palper, we show that this equilibrium need not be invoked and that changes in decay rate with changing pH merely result from radical protonation in acid. We have also made a detailed comparison of meta and para isomeric radicals by mleasuring their adsorption spectra, acidbase equilibria, and stabilities as reflected in electron transfer rate constaints.
Experimental Section All solutions were prepared i n triply distilled water and deoxygenated with prepurified nitrogen. Pyridine derivatives were obtained from Aldrich Chemical Co. and from Eastman Organic Chemicals. The computer-controlled pulse radiolysis system developed in these laboratories has previously been ~iescribed.~ Irradiations were carried out with 0.l-l.psec pulses of 2.8-MeV electrons from a Van de Graaff accelerator, (and time-dependent optical absorption spectra were measured for each compound as a function of pN. Extinction coefficients, E , were datermined by thiocyanate dosimetry assuming t 4 8 0 ( ~ ~ s7600 ) 2 - M - l cm-l. Dissociation constants were determined from variations in extinction coefiicienbr with changing pH. Titration curves were plotted for best fit with these experimental data using a Hewlett-Peckard 9100A calculator and plotter and the equation EObsd
=
k R 2 4 -i-
EtrnK*/[H*I
+ E*K1Kz/[H'l2)/(1 + Ki/[H+]+ KiK2/[H'12)
where HzA, H A , antl A represent three acid-base forms and K 1 and Kz are the dissociation constants. Decay kinetics were determined over a tenfold range of radical concentrations and electron transfer kinetics over a fivefold range of solute concentrations.
Formation of Pysidinyl Radicals Pyridine derivatives can be reduced in aqueous solution by eaq- (reaction 1/. While the reaction of eaq- with pyridine itself is only moderately rapid ( k = 1 X lo9 M-l seeA1)the presence of carboxy and carbamoyl substituents on the ring increases the rate to the diffusion-controlled limit. Nicotinic antl isonicotinic acid, the associated amides, and NAD" all react with eaq- at rate constant > l o 1 0 M - ~ e c - ~'In. ~order , ~ to properly study radicals produced from eaq- reactions it is necessary to eliminate interference from OH reaction with the pyridines. This can be achieved by adding an OH scavenger whose intermediate has no absorption which overlaps that of the radical under study. t BuBH i s especially suitable because it produces an intermediate which is essentially transparent in the wavelength
'
The Journal of Physical Chemistry. Vo/. 78, No. 22, 1974
region above 250 nm. However, this intermediate becomes involved in cross reactions with pyridinyl radicals and affects the decay kinetics. This difficulty can be avoided if a scavenger is used which reacts with H and OH to yield an intermediate which also reduces the pyridine by electron transfer. One may thus produce a one-radical system. Formate, for example, yields c0,- radicals upon reaction with OH and H, and these in turn efficiently reduce NAD+ and other pyridinium c o m p o ~ n d s . ~ However, ~ * ~ ~ the use of formate is limited to solutions at pH > 3.5 because in the acid region eaq- is converted to H by reaction with H+ and formic acid (pK = 3.7) reacts with H very slowly. i-PrOH, however, reacts efficiently with both OH and H to produce an intermediate which exhibits little absorption at wavelengths greater than 300 nm and is known to transfer electrons efficiently in many systems (see, e.g., ref 8). It was decided, therefore, to examine rates of electron transfer from the (CH&&OH radical to pyridine derivatives in order to determine the proper conditions for producing a one-radical system. For these experiments, solutions wePe prepared with iPrOH concentrations of 0.5 M and were saturated with NzO. The pyridine concentration was limited to M. At neutral pH all eaq- is converted to OH by NzO while in the acid region eaq- is converted to H by reaction with H+. Both OH and H react efficiently with i-PrOH to yield (CH&cOH. The pyridinyl radicals (Pyr ' ) absorb strongly around 400 nm and it is, therefore, possible to monitor without interference the formation of pyridinyl by the reduction of pyridinium cation (Pyr+)
-
(CH,),&OH
+ Pyr'
-
(CH,),CO i-
The hydroxyisopropoyl radical dissociates into (CH3)zCO(pK = 12.2) which is known to be a stronger reducing agent. By adjusting the pH to 2 1 3 one can measure the rate for the reaction (CH,)2b0-
+
Pyr'
-
(CH3&CO + PyE
(3)
In order to correlate structure with rate constant, studies were carried out at several pH values with pyridines having carboxyl and carbamoyl substituents either meta or para to the nitrogen. With each compound a series of solute concentrations between 1 X and 1 X M were used. Both the formation kinetics and the maximum optical density after formation were observed. A t lower concentrations complete electron transfer was not achieved because part of the (CH)&OH radicals disappeared by radical-radical reactions. This competing process also causes the formation kinetics to appear to be too rapid. At the higher solute concentrations reaction 2 or 3 becomes quantitative, and the same rate constants were determined over a fivefold range of concentrations. The results, summarized in Table I, show a clear distinction between the reactivities of (CH&COH and (CH3)&0- and suggest several trends in reactivity. Pyridine derivatives in which the nitrogen is neutral, i.e., nonsubstituted and nonprotonated, are not reduced by (CH&COH, Le., k < 1 X lo6 M - l sec-l, but can be reduced by (CH3)&O- at moderate rates, k los M - l sec-'. When the nitrogen is positively charged, through protonation or methylation, the r e d u d o n by (CH3)&OH becomes efficient. The rate constants are again increased, although only slightly, upon protonation of a carboxyl group on the ring. In all cases, however, the para isomer
-
2213
Substituted Pyridinyl Radicals in P.queous Solutions
250
300
390
400
450
500
&(nm)
accepts an electron (-5-10 times more rapidly than the meta isomer This behavior correlates with the difference in redox potmtials f w the two isomers, e.g., as determined for nicotinic axial isonicotinic acid. At pH 1 the polarographic half-wave potentials for the reduction of nicotinic and isonicotinic acid are -1.08 and -0.80 V (us. standard calomel electrode), re~pectively.~ Pulse polarographic experimentslO with (CH2)zCOI-I yielded a value of Ellz = -1.30 V, which indicates that both acids should be efficiently reduced hy this radical. In neutral solutions, on the other hand, the E Tj z values for nicotinic and isonicotinic acid are -1.66 and -3.56 V, respectively, and thus no electron transfer can be expected. The E1/2 for (CH3)zCO- is -2.2 V, and again reduction becomes possible. The half-wave potential for c0,- is comparablelo to that for (GH3)&ll-H and, therefore, a similar behavior in the electron transfer reactions is expected. Indeed, a qualitative obsenratior has heen made which suggests that COzcan transfer electron dficiently to pyridinium ions but not to pyridines.4 A rate constant of 1.6 x 109 M I ' sec-' for the electron %raidert o NAD+ has been reported2
issociation Constants Pyridingl radicals were produced in irradiated aqueous solutions by readion of pyridine derivatives with eaq- and, whenever possible, also by their reactions with ( CH3)2cOH.Transient absorption spectra were monitored at various p%d values i , order ~ to detect related shifts in absorbance and these shifts were then used for the determination of dissociation constants. After the pK values had been established spectra were recorded at the pH regions where one form 3f the radical predominates. The spectra observed with solutions of isonicotinic acid are shown in Figwe i In the acid region electron transfer from ~ ~ ~ i s rapid ~ )and 2all primary ~ Q radicals ~ ultimately yield p ~ r ~ In~ neutral ~ ~ ~solutions y ~ . the electron transfer does not take place, and the absorbance observed rOH or t-BuOH was identical. 60- predominates transfer is density increases accordingly, although no shift in the spectrmn could be detected between pH 8 and pH 44. The spectrum in this region is in good agreement with that reported previously.3 Changes in the absorbance PI, 405 and 425 nrrr with pH were used to determine the pM value4 as shown in the bottom part of Figure 1. The pM O F 6.3 faad to be determined in the presence uOH, becarise with i-PrOH as the pH decreases and the isonicotinatc ion protonates on the nitrogen (pK = 4.861, electron transfer begins to take place; and the ab-
5,000
4.000
'5
3.000
-5 "
2,000
1.000
0
2
0
2
4
6
E
IC
PH
Flgu;e 1. (Top) Transient absorption spectra of the acid-base forms of the 4-carboxypyridinyl radical. Observed with 0.2-1 X M solutions of isonicotinic acid. (0)Spectrum observed at pH 8.8 in the presence of 0.5 M t-BuOH. An identical spectrum was obtained at pH 8.0 in the presence of 0.5 M i-PrOH. In both cases only the eaqreacted with the isonicotinic acid and no electron transfer from the alcohol radicals took place. At pH 12.7 with CPrOH electron transfer was rapid and an identical spectrum was obtained with the same extinction coefficients (Le.,optical densities 2.3 times higher). At pH 13 and 14 the spectra were also identical. (0)Spectrum at pH 2.9 in the presence of 0.5 M i-PrOH. Electron transfer from the alcohol radical was rapid in this case. (A) Spectrum at Ho = -0.8 with perchloric acid and 0.5 M i-PrOH. Again the electron transfer was rapid. (Bottom) Effect of pH on the transient absorption. (0)Determined at 405 nm with solutions containing 1 X M isonicotinic acid and 0.5 M t-BuOH. The titration curve was calculated from the plateau values using p K = 6.3. (0)determined at 425 nrn with solutions containing 1 X M isonicotinic acid and 0.5 M CPrOH, The curve was calculated using p K = -0.17. For pH
