J . Pkys. Chem. 1987, 91, 4 156-4 160
4156
Reactions of Iron Porphyrins with 'CF,, CF,O,', and CBr,O,' Radicals D. Brault*+and P. Neta*t Chemical Kinetics Division, National Bureau of Standards, Gaithersburg, Maryland 20899, and Laboratoire de Biophysique, INSERM U.201, CNRS UA.481, MusPum National d'Histoire Naturelle, 75005 Paris, France (Received: February 5 , 1987)
The reactions of ferric and ferrous deuteroporphyrin (PFe"', PFe") with alkyl and peroxyl radicals derived from CF3Br and CBr, were studied by kinetic spectrophotometric pulse radiolysis in aqueous alcohol solutions. PFe" reacts with 'CF, radical at nearly diffusion controlled rate ( k = 2 X lo9 M-' s-' ) to form a metal-carbon bonded complex. The PFe1"CF3 adduct subsequently reacts with another PFe" ( k = 5 X lo6 M-' s-I) presumably to form the carbene intermediate PFe1'CF2which further hydrolyzes. The final products are PFe"' and PFe"C0. 'CF, radicals also react with PFe"' ( k = 4.5 X lo8 M-' s-l) to yield an oxidized product. The initial product undergoes a slow reaction ( k = 2.8 X lo3 s-I) ascribed to ligand exchange. 'CBr, radicals do not react with PFe"' on the pulse radiolysis time scale ( k < lo6 M-' s-' ). The peroxyl radicals CF302' and CBr30,' oxidize PFe"' with reaction rate constants of 3.9 X IO8 and 2.8 X lo8 M-' s-', respectively. Similar reactions were reported for other peroxyl radicals. These reactions were used in competition kinetic experiments to obtain the rate constants for hydrogen abstraction from linolenic acid. The rate constants for the reaction of linolenic acid with CF302' and CBr302' are 6.9 X lo6 and 1.2 X lo6 M-l s-' , r espectively. The reactions are discussed with regard to the reactivity and possible toxicity of halogenated compounds.
Introduction The reactions of alkyl and haloalkyl radicals and their peroxyl derivatives with metal complexes and particularly with metalloporphyrins have important bearing on both organometallic chemistry1*2and biological degradation of halogenated comp o u n d ~ . ~ " Studies on the reactivity of porphyrins have led to several new complexes in the iron series2 Adducts of carboncentered radicals to f e r r ~ u s and ~ - ~ferric porphyrins8 have been described. They are characterized by a u-bond between the carbon and the iron.l0V1l The stability of adducts formed from ferrous porphyrins depends on the substituents on the ~ a r b o n . ~When -~ halogens are present, further reductive elimination may lead to carbene complexes characterized by a metal-carbon double bond.I2-l4 All alkyl radicals react rapidly with ferrous porphyr i n ~ . ' - ~In contrast, the reaction with ferric porphyrins depends strongly on the substituents on the carbon. For example, methyl radicals react very rapidly to form an adducts while 'CC13 radicals do not reacts7 The peroxyl radicals oxidize the ferric porphyrins with rate constants that depend on the electronegativity of the substituent^.^^ In some cases, evidence was found for inner-sphere electron t r a n ~ f e r . ' ~ .The ~ ~ reactions of peroxyl radicals with ferrous porphyrins cannot be studied since these compounds are quickly oxidized by oxygen to the ferric form.18 The toxicity of halogenated alkanes originates from their metabolism by ferrous cytochrome P450 which leads to the sequential formation of alkyl and peroxyl The latter radicals induce extensive chain lipid peroxidation in membranes originating from attack on unsaturated fatty acids. Back-reaction of either the alkyl or the peroxyalkyl radicals with cytochrome P450 is expected to limit the development of this deleterious chain process and is thus an important factor in the overall toxicity of halogenated c o m p o ~ n d s . ~ ~ ' ~ In this paper, we report on the reactions of iron porphyrins with haloalkyl and peroxyl radicals derived from a powerful toxic agent, CBr4, and a widely used refrigerant and fire extinguisher, CF,Br. The 'CBr,, CBr302', and CF302*radicals were found to behave similarly to related radicals derived from carbon tetrachloride. In contrast, the reactions of 'CF, radicals with iron porphyrins and the reactivity of the resulting adducts depart from those previously observed in the case of alkyl and haloalkyl radicals. In particular, the PFeII'CF, complex is shown to undergo reduction. These results are discussed with regard to the mechanism of carbene complex formation and possible toxicity of CF,Br. Museum National d'Histoire Naturelle (address for correspondence). Visiting scientist at the National Bureau of Standards. 'National Bureau of Standards.
0022-3654/87/2091-4156$01 .50/0
Experimental Sectionz1 Materials. Iron deuteroporphyrin (3,7,12,17-tetramethylporphine-2,18-dipropanoicacid) has been largely used as a model of hemoproteins for its similitude to the actual biological compound and its higher stability. Ferrideuteroporphyrin IX chloride, PFe"'C1, and the p o x 0 dimer of ferrideuteroporphyrin IX dimethyl ester, (PDMEFe111)20,were prepared as described elseSolutions were made in 1:1 v/v mixtures of 2-propanol and water. PFe"'C1 was used for the experiments in alkaline solutions (0.05 M NaOH) and the dimethyl ester for the acidic solutions (0.1 M HC104). In these aqueous-alcohol solutions, the porphyrin monomerizes and undergoes counteranion exchange as discussed before.20 The resulting species in solutions are PFe'*10CH(CH3)2((CH3)2CHOH) and [PFe11'((CH3)2CHOH)2]+ in alkaline and acidic solutions, respectively. They will be abbreviated as PFe"' regardless of the associated anion or coordinated (1) Kochi, J. K. Organometallic Mechanisms and Catalysis; Academic: New York, 1978. (2) Brothers, P. J.; Collman, J. P. Acc. Chem. Res. 1986, 19, 209. (3) Slater, T. F. Biochemical Mechanisms of Lioer Injury; Slater, T. F., Ed.; Academic: London, 1978; p 1. (4) Recknagel, R. 0.;Glende, E. A,, Jr.; Hruszkewycz, A. M. In Free Radicals in Biology; Pryor, W. A., Ed.; Academic: New York, 1977; p 97. (5) Cheeseman, K. H.; Albano, E. F.; Tomasi, A,; Slater, T. F. Enoiron. Health Perspect. 1985, 64, 85. (6) Brault, D. Enuiron. Health Perspect. 1985, 64, 53. (7) Brault, D.; Bizet, C.; Morliere, P.; Rougte, M.; Land, E. J.; Santus, R.; Swallow, A. J. J . A m . Chem. SOC.1980, 102, 1015. (8) Brault, D.; Neta, P. J . A m . Chem. Soc. 1981, 103, 2705. (9) Brault, D.; Neta, P. J . Phys. Chem. 1982, 86, 3405. (10) Lexa, D.; Mispelter, J.; Savtant, J. M. J . A m . Chem. SOC.1981, 103, 6806. (1 1) Cocolios, P.; Laviron, E.; Guilard, R. J . Organomet. Chem. 1982,228, c39. (12) Brault, D.; Rougte, M.; Momenteau, M. J . Chim. Phys. Phys.-Chim. Biol. 1971, 68, 1621. (13) Mansuy, D.; Lange, M.: Chottard, J. C.; Guerin, P.; Morliere, P.; Brault, D.; Rougee, M. J . Chem. Soc., Chem. Commun. 1977, 648. (14) Mansuy, D.; Lange, M.; Chottard, J. C.; Bartoli, J. F.; Chevrier, B.; Weiss, R. Angew. Chem., Int. Ed. Engl. 1978, 17, 781. (15) Brault, D.; Neta, P. J . Phys. Chem. 1984, 88, 2857. (16) Brault, D.; Neta, P. Chem. Phys. Lett. 1985, 121, 28. (17) Alfassi, Z. B.; Harriman, A,; Mosseri, S.; Neta, P. Znt. J . Chem. Kinet. 1986, 18, 1315. (18) Brault, D.; Rougte, M. Biochemistry 1974, 13, 4591. (19) Brault, D.; Neta, P.; Patterson, L. K. Chem.-Biol.Interact. 1985, 54, 289. (20) Bizet, C . ; Morlitre, P.; Brault, D.; Delgado, 0.;Bazin, M.; Santus, R. Photochem. Photobiol. 1981, 34, 315. (21) The mention of commercial material or equipment does not imply recommendation or endorsement by the National Bureau of Standards, nor does it imply that the equipment or material identified are necessarily the best available for the purpose.
0 1987 American Chemical Society
The Journal of Physical Chemistry, Vol. 91, No. 15, 1987
Reactions of Iron Porphyrins with Haloalkyl Radicals solvent molecules. The reduced form, PFe", in alkaline solutions was prepared under anaerobic conditions using sodium dithionite (Fisher). A threefold excess of the reducing agent was used for the pulse radiolysis experiments. The CF3Br gas (Freon 13B1) was purchased from Dupont and CBr, from Eastman. Linolenic acid (98%) was obtained from Sigma. Water was purified by a Millipore Milli-Q system. For experiments involving peroxyl radicals, solutions were bubbled with a mixture of CF,Br and Oz (4: 1) delivered by flowmeters. Measurements. Steady-state radiolysis experiments on alkaline solutions of PFe" were performed by using a Gammacell 220 "20 source delivering about 10 krd/min. Solutions of PFe"' in quartz optical cells (2 mm) capped with rubber septa were first bubbled with CF,Br through a needle. Quantitative reduction to the ferrous state was then achieved by adding aliquots of a dithionite solution. The reduction was followed spectrophotometrically.18 In some instances, an excess of sodium dithionite was used. Optical spectra were recorded on a Cary 219 spectrophotometer. The pulse radiolysis experiments were carried out with 50-11s pulses of 2-MeV electrons from a Febetron 705 accelerator. The dose used for kinetic experiments was usually 500 rd/pulse, determined by KSCN dosimetry. The solution flowed continuously through the irradiation cell (2-cm optical path length) to assure a fresh sample for each pulse. Cutoff filters were used to avoid illumination of the solutions in the Soret region. The optical detection consisted of a 300-W xenon lamp, a Kratos monochromator, and RCA 4840 photomultiplier. The signals were digitized with a Tektronix 7612 transient recorder and processed with a PDP 11/34 computer. Radical Production. The main species produced in irradiated aqueous 2-propanol solutions are e; and (CH,),COH radicals. The latter are formed by the radiolysis of 2-propanol and also by scavenging of the H' and OH' produced by water radiolysis.zz In deoxygenated solutions, the solvated electrons react rapidly with CF3Br or CBr, to form 'CF, or 'CBr, radicals, respectively, according to the general reactionz3 RX
+ e,-
-
R'
+ (CH,),CO'-
-
'CF,
T l3t2-
L
X
1
r
VI 1
'.
0 (v
0
c
x -
0
10
30
20
40
0
50
. I-.
0
1'
iPFe
T I M E (PS)
'W. V
z -
2 .
(M)x
lo4
ma K
2 a
Y
a
f
L
L
K
e
h 0
2
4
6
6
T I M E (ms)
Figure 1. (a, c) Absorbance changes (A = 460 nm) following pulse radiolysis of 1 X M PFe" in CF,Br-saturated alkaline ([NaOH] = 0.05 M) aqueous 2-propanol (6.5 M) solutions. The ferrous form was prepared from PFe"' with sodium dithionite (3 X lo4 M). Dots are experimental points. Full lines are first-order fits. (b, d) Plots of the pseudo-first-order constants vs. the PFe" concentrations for the fast (b) and slow (d) processes. The dose per pulse was about 0.5 krd.
+ X-
The fate of the (CH3)&OH radicals depends on pH and on the nature of the haloalkane present in solution. In alkaline solutions these radicals deprotonate (pK = 12.2) to form the more strongly reducing (CH3)2CO'-radicalsz4which react with CF,Br according to CF,Br
4157
+ Br- + (CH&CO
(2)
The rate constant k was reportedz5to be approximately 3 X lo8 M-I s-l. The neutral radical (CH3)&OH does not react with CF3Br. As a consequence, full conversion of the primary products of radiolysis to the 'CF3 radicals can be achieved only in alkaline solutions. Both the neutral and the deprotonated forms of the 2-hydroxy-2-propyl radical react with CBr,, leading to the 'CBr, radical. Thus, even at low pH, when solvated electrons are scavenged by protons to form H' atoms, these are converted to (CH&COH radicals through reaction with 2-propanol and full conversion to the 'CBr, radicals is achieved. Haloalkyl radicals react with oxygen at nearly diffusion controlled rate.z6,z7 Thus, in aerated solutions, the CF30z' and CBr,O2' peroxyl radicals are formed. Results and Discussion Radiolysis of Deoxygenated CF3Br-Sat urated Solutions of PFe". Ferrous deuteroporphyrin was found to react only very slowly with CF,Br,25 so that experiments involving CF,Br-satu(22) Neta, P. Ado. Phys. Org. Chem. 1976, 12, 223. (23) Anbar, M.; Bambeneck, M.; Ross, A. B. Natl. Stand. ReJ Data Ser.
(US.Natl. Bur. Stand.) 1973, NSRDS-NBS 43. (24) Lilie, J.; Beck, G.; Henglein, A. Ber. Bunsenges. Phys. Chem. 1971, 75, 458.
( 2 5 ) Huie, R. E.; Brault, D.; Neta, P. Chem.-Bid. Interact., in press. ( 2 6 ) Packer, J. E.; Willson, R. L.; Bahnemann, D. Asmus, K. D. J . Chem. Soc., Perkin Trans. 2 1980, 296. (27) Monig, J.; Amus, K. D.; Schaeffer, M.; Slater, T. F.; Willson, R. L. J . Chem. SOC.,Perkin Trans. 2 1983, 1133.
-10
/
-1
450
500 A
(m)
550
600
650
Figure 2. Differential absorption spectra recorded after radiolysis of PFe" in CF,Br-saturated solutions (see Figure 1 for composition): and 0 , left scale, 2-cm optical cell, transient spectra recorded 30 ps and 9 ms after pulse irradiation, respectively; -,right scale, 2-mm optical cell, differential spectrum derived from the steady-state radiolysis experiments described in Figure 3: spectrum after 2-min irradiation minus original PFe" spectrum.
--
rated solutions of PFe" can be carried out over several hours without noticeable evolution in the solution composition. Kinetic spectrophotometric traces taken at different time scales indicate the Occurrence of two consecutive reactions. Typical traces taken at 460 nm are shown in Figure la,c. The traces shown, as well as others taken at different wavelengths, were found to fit first-order kinetics in both the fast and the slow processes. The rate of both reactions were found to depend fairly linearly on the porphyrin concentration. The small nonzero intercept may reflect self-reaction of the 'CF, radicals (Figure lb) or of the intermediate species formed (Figure Id). From the plots in Figure lb,d we derive second-order rate constants of (2.0 f 0.3) X lo9 and (5.1 f 0.8) X lo6 M-' s-l, respectively. Transient differential spectra were monitored at 30 ps and 9 ms after the pulse (Figure 2). The initial spectral change corresponds to the bleaching of the ferrous porphyrin absorption (520 and 560 nm) and buildup of absorption at 540 nm and in the range of 450-500 nm. This initial change must correspond to the addition of 'CF, radicals to the iron porphyrin PFe"
+ 'CF3
-
PFeII'CF,
(3)
where CF, in the product stands formally for CF,-. Reaction 3, with k3 = 2.0 X lo9 M-I s-', is parallel t o those described before
4158
The Journal of Physical Chemistry, Vol. 91, No. 15. 1987
Brault and Neta 4
40.2
W
'.2 W
V
D
a
v)
z
W
m
0
K
9 W
0
u z a m a 2 0 v)
m
a
D .l z
v)
m
a
0
m 0 A
I
A
(nm)
Figure 3. Spectral evolution upon steady-stateirradiation of 9.2 X M PFe" in CF3Br-saturated alkaline ([NaOH] = 0.05 M) aqueous 2-propanol (6.5 M) solution: (-) no irradiation (PFe"), (- - -) I-min and (---) 2-min irradiation; (--) after air bubbling. The ferrous form was prepared from PFe"' by quantitative reduction using sodium dithionite (dose rate = 10 krd/min, 2-mm optical cell).
for similar carbon-centered radicals. As examples, the 'CH, and 'CCl, radicals also react with PFe" with rate constants of about 2 x 109 M-1 s-1 (see ref 8 and 7). In all cases, the products exhibit absorption at 540 nm. While the CH, adduct is stable under anaerobic conditions,* the CC13adduct is unstable.' The present results indicate that the CF, adduct reacts further with an additional molecule of ferrous porphyrin. The final spectrum monitored at 9 ms (Figure 2) shows intense absorption at 595 nm and in the 460-490-nm range, suggesting formation of ferric porphyrin. The final products of this reaction are further identified by spectrophotometric y-radiolysis experiments, as described below. Steady-state radiolysis experiments were carried out under two different conditions. In one case, the ferric porphyrin was reduced to the ferrous form quantitatively and in the other experiment fourfold excess of dithionite was used. The spectral changes occurring upon irradiation are shown in Figures 3 and 4, respectively. The difference between the final and initial spectrum in Figure 3 is in very good agreement with the differential spectrum recorded in the pulse radiolysis experiment 9 ms after the pulse (see Figure 2), indicating that no other reaction takes place over intermediate time scales. The sharp Soret peak at 398 nm shows that, in addition to ferric porphyrin, another product is formed in the process. The experiment shown in Figure 4 is carried out with excess sodium dithionite which reduces the ferric porphyrin. The results confirm that the ferric form was formed under the previous conditions (Figure 3). Small residual absorption at 602 nm is attributed to the formation of side products. The elimination of the ferric porphyrin from the system makes it easier to characterize the second major product which remains present as shown by the strong absorption at 398 nm. Sharp peaks in this region have been reported for carbonyl complexes of ferrous porphyrins.28 In fact, chemical preparation of PFe"C0 by dithionite reduction of PFe"' solution containing C O under conditions similar to those used in the y-radiolysis experiment confirms the identity of the spectra (Figure 4). As expected, in both experiments PFeI'CO was rapidly oxidized to PFeI" upon exposure to air. The recovery of PFe"I after the radiolysis was about 90%, and a small amount of side products absorbing above 590 nm was apparent (Figure 3). It should be pointed out that reduction by dithionite is too slow to interfere in the pulse radiolysis experiment even if excess dithionite is used. In fact, dithionite reduction was visually observed to take tens of seconds. (28) RougBe, M.; Brault, D. Biochemisfry 1975, 14, 4100
(nm)
Figure 4. Spectral evolution upon steady-state irradiation of 8 X M PFe" in CF,Br-saturated alkaline ([NaOH] = 0.06 M) aqueous 2propanol (5.2 M) solution: (-) no irradiation (PFe"); ( - --) 1-min and (---) 2-min irradiation; spectrum of chemically prepared PFe"C0 in solution of the same composition. PFe" was prepared with excess sodium dithionite (dose rate = 10 krd/min, 2-mm optical cell). (-e)
The conversion of the initial PFe"'CF, adduct to the final PFe"C0 product must occur in several steps. The rate-determining step involves the reaction of the adduct with excess PFe". This reaction takes place with k4 = 5.1 X lo6 M-I s-l and is not affected by excess dithionite. The most plausible mechanism is PFe"'CF,
+ PFe"
PFe"CF,
+ H20
-
-
PFe"CF, PFeI'CO
+ PFelI1 + F + 2H' + 2 F
(4) (5)
Reaction 4 may take place by outer-sphere electron transfer or by inner-sphere process accompanied with fluoride transfer. In any case, the reaction is expected to be relatively slow. The standard redox potential of the PFe"'CH,/PFe"CH, couple has been reported to be -0.76 V vs. SCE for the iron tetraphenylporphyrin complex, intermediate between the PFe"/PFe' and PFe"'/PFe" couples.I0 In the case of the CF3 adduct, the electronegative fluorine substituents are expected to increase the redox potential to a value near the one of the PFe"'/PFe" couple. The large excess of PFe" in our system and the cleavage of a carbon-fluorine bond are expected to drive reaction 4 to the right. It thus appears that the feasibility of reduction of PFe"'CX, complexes largely depends on the electronegativity of the substituents on the carbon. It is worth noting that such reactions were not observed previously although they may be more common as discussed later. This was made possible by some specific features of the system used: PFe" and CF,Br do not react together, all radiolytic species are converted to 'CF, radicals, and PFe"'CF, is stable enough to allow observation of steps 3 and 4 in succession. Reaction 5 is parallel to hydrolysis of other carbene adducts investigated before. Hydrolysis of PFe"CC1, has been observed in the same medium but has a much lower rate constant (1.2 X 10-4 s-I)*~ and has also been reported for CC12 adduct of ferrous cytochrome P450.30 Reactions of 'CF, and 'CBr, Radicals with PFe"'. The spectral changes observed upon pulse radiolysis of CF,Br-saturated alkaline solution of PFe"' are shown in Figure 5a. Kinetic traces showed a two-step process (see Figure 5b), and the spectra were taken after the completion of each of these reactions, Le., 90 ws and 1.7 ms after the pulse. Both spectra show bleaching of the ferric porphyrin bands at 475 and 585 nm and formation of product absorptions at 530 and 650-750 nm. The latter band is identical with that observed upon oxidation of PFe"' with CC1302'. Therefore, both the initial and the final products can be described as forms of (PFel")+. The rate constant for the first step was determined at various porphyrin concentrations and found to be (4.5 A 0.6) X IO8 M-' s-I. The second step took place with a rate (29) Vever-Bizet, C.; Brault, D., unpublished results. (30) Wolf, C. R.; Mansuy, D.; Nastainczyk, W.; Deutschmann, G.; U11rich, V. Mol. Pharmacol. 1977, 13, 698.
The Journal of Physical Chemistry, Vol. 91, No. 15, 1987 4159
Reactions of Iron Porphyrins with Haloalkyl Radicals
T I M E (ms)
I
500
600
700
800
1
The rate constants for reactions 6 and 7 are both somewhat higher than the rate constant found for reaction with CC1302'. This trend is in line with previous results on the rates of oneelectron oxidation of various organic compounds by the three peroxyl radicals.z5 However, the differences among the rate constants for reaction with PFe"' are smaller than those found for the other compounds. These results suggest that oxidation of the ferric porphyrin by the peroxyl radicals may take place by an inner-sphere substitution mechanism as formulated previously.'6J7 Competition Experiments with Linolenic Acid. Since the kinetics of reactions 6 and 7 can be monitored spectrophotometrically, these reactions may serve in competition kinetic experiments to determine the rate of reaction of the peroxyl radicals with lipids. Recently, we have utilized this technique to obtain the rate constants for reaction of CCl3OZ*with several unsaturated fatty acids. For comparison, we have determined the rate constants of CF3Oz' and CBr302' reactions with linolenic acid. CX3O2'
A ("m)
Figure 5. Pulse radiolysis of 1 X lo4 M PFe'" in CF3Br-saturated alkaline ([NaOH] = 0.05 M) aqueous 2-propanol (6.5 M) solutions: (a) differential transient absorption spectra recorded 90 ps (m) and 1.7 ms ( 0 )after the pulse (dose = 1.5 krd); (b) absorbance changes (A = 520 nm) following the pulse (dose = 0.5 krd).
of (2.8 f 0.5) X lo3 s-' which was independent of porphyrin concentration and of dose per pulse. The first reaction may be similar to that described for the reaction with 'CH3, Le., forming the PFeIVCF3adduct.8 However, the spectrum of the product is considerably different from that observed with CH3 and resembles that of an oxidized porphyrin.15 This might be a result of the large electronegativity of the CF3 moiety, leading to strong polarization of the iron-carbon bond. An alternative mechanism is oxidation accompanied by fluoride transfer to yield (PFe"')+F and :CF2. As no fluoride excess is present, this complex is likely to exchange F from a solvent molecule, accounting for the slow step observed. The :CF2 might undergo hydrolysis to CO. To examine this possibility, a CF3Br-saturated solution of PFe"' was irradiated to achieve only partial conversion and then reduced with excess dithionite. If C O is present, it should react with the PFe" to form PFeIICO, which is easily identified by its characteristic absorption at 398 nm (see above). In fact, the experiment showed a small yield of CO, suggesting that the latter mechanism can take place to some extent. No evidence was found for the reaction of 'CBr, radicals with PFe"' in the pulse radiolysis of 2-propanol/water acidic solutions containing CBr4. This finding is similar to that observed with 'CC1, radicals, Le., k < lo6 M-' S-'. Oxidation of PFe"' by CF302' and CBr302'. In a previous studyI5 we have reported the kinetics and spectral changes for oxidation of PFelI1by CC130; and several other peroxyl radicals in alkaline and acidic solutions. CF30z' and CBr3O2*have been shownz5 to react by one-electron oxidation more rapidly than CCl,Oz'. Therefore, they are expected to oxidize PFe"' in the same manner. Pulse radiolysis experiments with alkaline solutions of PFe"' saturated with a mixture of CF3Br and Oz (4:l) showed buildup of absorption at 700 nm similar to that observed beforeI5 with CC1302'. From the rate of formation as a function of porphyrin concentration we derived a rate constant of k6 = (3.9 f 0.5) X lo8 M-I s-I.
+
-
+ CBr,0;
-
PFe"' CF3OZ' (PFe"')+ + C F 3 0 F (6) Experiments with aerated acidic solutions of PFe"' in the presence of 10 mM CBr, showed formation of the 660-nm absorption characteristic of the oxidized species in acidic solutions. The kinetic analysis gave k7 = (2.8 f 0.4) X lo8 M-' s-'.
PFe"'
(PFe"')'
+ CBr30,
(7)
The product of reactions 6 and 7, (PFe"')+, has been suggested to have a wradical cation structure rather than FeIV character (see discussion in ref 15).
+ LH
4
CX302H
+ L'
(8)
Solutions containing 7 X M PFe"' in 1:l 2-propanol/water, 0.05 M NaOH, and 0-0.02 M linolenic acid were saturated with CF3Br/02 (4: 1) mixtures and pulse-irradiated. From the dependence of the yield of (PFe"')', monitored at 700 nm, on the concentration of linolenic acid according to the relation Ao/A = 1 (k8[1in])/(k6[PFe"']), the rate constant for reaction of CF30{ with linolenic acid in alkaline solution was found to be (6.9 f 0.9) X lo6 M-' s-l. To determine the rate constant for reaction of CBr302*with linolenic acid, we carried out similar experiments with aerated solutions of the porphyrin (1 X M) containing CBr, (0.01 M), 0.1 M HC104,and 04.04 M linolenic acid. The rate constant was calculated to be (1.2 f 0.4) X lo6 M-' s-l. In the latter experiments, as in the previous experiments with CCl,O; in acid solutions, the radical produced from linolenic acid subsequently forms a peroxyl radical which also reacts with the porphyrins but at a slower rate. On the other hand, the experiments with CF3O2. carried out in alkaline solutions did not exhibit the slower oxidation of the porphyrin by the fatty acid peroxyl radical. The reason for the absence of this process at high pH may be that the reaction is acid-catalyzed as observed for other nonhalogenated peroxyl radicals. l 6 Comparison of the rate of hydrogen abstraction from linolenic acid by the three halogenated peroxyl radicals CF30;, CC130;, and CBr3O2* shows that these follow the same trend as that observed in the electron-transfer reactions, Le., F > Br > C1.
+
Conclusion Formation of Metal-Carbon Complexes of Iron Porphyrins. Alkyl and haloalkyl radicals ('CH,, 'CF,, 'CC13, CF,CHCl, ...) react with PFe" with rates near the diffusion-controlled limit ( k = 2 X lo9 M-' s-I). The fate of the adducts, which contain a Fe-C bond, depends considerably on the alkyl substitution. The PFe111CH3adduct is stable under anaerobic conditions. The CC13 adduct, on the other hand, cannot be isolated. The PFe111CF3 adduct was found to react with PFe" to form the carbene complex PFeI1CFz, which hydrolyzes to give PFeIICO as the final product (reactions 4 and 5). The reduction of PFe111CX3complexes by ferrous porphyrin is likely to occur in the chemical preparation of the carbene complexes. Thus, when the compounds are formed by reacting the ferrous porphyrin with the haloalkane in the presence of excess reducing agent, the following sequence of reactions is likely to occur: reduction of the haloalkane by PFe" leading to 'CX, radicals, scavenging of the radicals by excess PFe" to yield PFe"'CX3, and then reduction of the latter compound to PFeCXz by excess PFe". The reducing agent allows conversion of the PFe"' formed at each of these steps to the ferrous form. By contrast with the apparently high and unselective reactivity of alkyl and haloalkyl radicals with PFe", these radicals exhibit high selectivity in their reactions with PFe'I'. While 'CCl,, 'CBr,, and CF3CHC1 do not appear to react with PFe"' (k < lo6 M-' s-l), 'CH3 and 'CF3 radicals react very rapidly. The adducts
J . Phys. Chem. 1987, 91, 4160-4165
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formed, PFeI'CH, and PFexVCF3,are much less stable than those derived from the addition of those radicals to PFe". Relevance to the Toxicity of Halogenated Alkanes. The difference in reactivity of these radicals with PFe"' has important bearing on the toxicity of the related halocarbons. The first step in the metabolism of halogenated alkanes is their reduction by ferrous cytochrome P450, leading to radicals and the ferric hemoprotein. Further, peroxyl radicals are formed and attack the fatty acids, which results in deleterious chain lipid peroxidation. The effect of oxygen concentration in the development of these reactions has been d i s c ~ s s e d . ~At J ~ high oxygen concentration the alkyl or haloalkyl radicals are converted to the peroxyl radicals near the ferric cytochrome P450, which is likely to scavenge them before they could diffuse through the membrane. Consequently, the damage on the membrane is greatly reduced. This hypothesis is supported by studies on biological system^.^',^^ This mechanism
of toxicity holds for CC14 and very likely also for CBr4. Indeed, the latter compound as well as 'CBr, and CBr302' radicals behaves similarly to CC14 and related radicals. The metabolism of CF,Br might be quite different. Firstly, as deduced from the reactivity with ferrous porphyrin, it is not expected to react rapidly with ferrous cytochrome P450 to yield 'CF, radicals.25 Secondly, if formed, the radicals should back-react very rapidly with the ferric cytochrome P450 and will not be able to induce lipid chain peroxidation. The oxidized cytochrome P450 formed in this reaction could be converted to the initial ferric form by enzymatic reduction. If any cytochrome P450 is destroyed in this process, the result will be less deleterious than lipid peroxidation. The toxicity of halogenated compounds can thus be evaluated from their reactivity toward biological reducing agents, such as ferrous cytochrome P450, and from the reactivities of the related haloalkyl and peroxyl radicals.
(31) De Groot, H.; Noll, T. Biochem. Biophys. Res. Commun. 1984,119, 139. (32) Noll, T.; De Groot, H. Biochim. Biophys. Acta 1984, 795, 356.
Acknowledgment. The research described herein was supported by the Office of Basic Energy Sciences of the U.S. Department of Energy.
Lean Premixed Laminar Methanol Flames: A Computational Study Jim 0. Olsson,* Ingrid B. M. Olsson, and Lars L. Andersson Department of Physical Chemistry, Chalmers University of Technology, S-412 96 Gothenburg, Sweden (Received: September 4, 1986)
Three experimental premixed laminar methanol flames at 40 Torr, measured in detail by Vandooren, Balakhin, and Van Tiggelen, were studied computationally. The equivalence ratios of the flames were 0.89 (l), 0.36 (2), and 0.21 (3). Flame 3 seemed to be the flame with the highest experimental accuracy. A time-dependent flame code with an implicit description for both chemistry and transport allowed extensive computations. Two kinetic mechanisms for methanol combustion were used to compute the species profiles. The first was based on the mechanism compiled by Westbrook, Dryer, and Schugh (WDS), but with 5 times the rate constant for the reaction HCO + M. The second mechanism was compiled by Dove and Warnatz (DW). Strikingly, the experimental CH20H maxima were much smaller than the corresponding computational maxima. The smallest differences were found in flame 3. In this flame the experimental CH20H maxima were about 70 and 20 times smaller than computational maxima found by using the WDS and DW mechanisms, respectively. The sensitivity analysis gave analogous results for the three flames. It was found that the CH20H profiles in the three flames were dominated by the reaction CH,OH + 0,. An increase in the rate constant of reaction CHzOH + O2decreased the CH20H maxima nearly linearly, leaving other species profiles almost unchanged. For this reaction a rate constant (WDS) of about 1.0 X 1014exp(-3019/T) cm3 mol-] s-l gave good agreement between the experimental and computational maxima for CHIOH in flame 3.
Introduction Methanol is a reference fuel in engine studies and its radicals, C H 2 0 H or C H 3 0 , are considered to be important in the ignition of other fuels.' Furthermore, many of the key reactions in methanol flames will also be important in other alcohol and hydrocarbon flames.2 Measurements of species in laminar methanol flames have previously been made by Akrich et al.,, Pauwels et al.,4 and Vandooren et al.s36 Andersson et al.7 studied experimentally and theoretically a stoichiometric low-pressure methanol flame. Dove, J. E.; Warnatz, J. Ber. Bunsen-Ges. Phys. Chem.1983,87, 1040. Westbrook, C. K.; Dryer, F. L. Prog. En. Combust. Sci. 1984, 10, 1. Akrich, R.;Vovelle, C.; Delbourgo, R. Combust. Flume 1978, 32, 171. Pauwels, J. F.; Carlier, M.; Sochet, L. R. J. Phys. Chem. 1982, 86,
4330.
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( 5 ) Vandooren, J.; Balakhin, V. P.; Van Tiggelen, P. J. Arch. Combust. 1981, I , 229-242.
(6) Vandooren, J.; Van Tiggelen, P. J. Sym. (In?.) Combust., [Proc.],18th 1980, 1981, 473. (7) Andersson, L. L.; Christenson, B.; H@lund, A,; Olsson, J. 0.;Rosengren, L. G. Prog. Astronaut. Aeronaut. 1985, 95, 164.
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Recently, Olsson et a1.' carried out a complementary investigation studying, the effect of water addition to methanol-air flames. Detailed computational studies of methanol combustion have been made by Westbrook and Dryer.gs'o Their mechanism is designed for handling many fuels and different physical conditions and it has been extensively used.2 Recently, Dove and Warnatz' presented another methanol mechanism in a computational study of premixed laminar methanol flames. The latter study and the one by Olsson et a1.' emphasized that the C H 2 0 H reactions with O2and M are important in methanol combustion. Unfortunately, the corresponding rate constants are the least certain, in the mechanism. According to Warnatz," their uncertainty is a factor of 10. In contrast, the other rate constants in the methanol mechanism have an uncertainty of about a factor of 3 or less. (8) Olsson, J. 0.; Karlsson, L. S.;Andersson, L. L. J. Phys. Chem. 1986, 90, 1458. (9) Westbrook, C. K.; Dryer, F. L. Combust. Sci. Technol. 1979, 20, 125. (10) Westbrook, C. K.; Dryer, F. L. Combust. Flume 1980, 37, 171. (,l 1) Warnatz, J. In Combustion Chemistry, Gardiner, Jr., W. C., Ed.; Springer: New York, 1984.
0 1987 American Chemical Society
