6697
Coenzyme B,, Model Studies. Equilibria and Kinetics of Axial Ligation of Methylaquocobaloxime by Primary Amines and 4-Substituted PyridineslS2 Kenneth L.
Donald Chernoff, David J. Keljo, and Roland G . Kallen'
Contribution from the Department of Biochemistry, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104. Received Nouember 8, 1971 Abstract: The ranges of equilibrium constants for the axial ligation reactions of methylaquocobaloxime at 25O, ionic strength 1.0 M , for a series of thiolate anions, 4-substituted pyridines, and aliphatic amines are 1-3 X lo5, 0.03-1.1 x 104, and 0.05-4.3 x 103 M-1, respectively. The dependence of the ligation equilibria upon ligand basicity within each series varies in the reverse order with p values of 0.18,0.21,and 0.38, respectively. The ranges of rate constants for axial ligation to methylaquocobaloxime are 4.3-7.5, 12.8-27.3, 49.6-55.2, and 92-200 M-I sec-I for RNH2, RS-, RSH, and X-py, respectively, and the dependence of these rate constants upon ligand basicity provides p values less than 0.1 within each series. The kinetic studies are consistent with a mechanism for these ligation reactions which is SN1 in nature. These results support significant contributions of metal-to-
ligand x bonding to the stabilization of transition states and products in the thiol and pyridine series. From studies of the ligation reactions at high pH values, rate and equilibrium constants for ligation to anionic methylaquocobaloxime have been measured as well as the values for the constants for proton dissociation from the planar ligand system for the complexes, Me(D2H2)L(L = RNH2, X-py). It is proposed that considerations regarding the assignment for the site of proton dissociation from Me(D&)HOH (pK' = 12.68) include the equatorial hydrogen-bonded proton.
T
he ligand substitution reactions of vitamin B12, its derivatives,4-8 and Blz model compounds, the c o b a l o ~ i m e s , ~are ~ ~ 0of interest from the points of view of the mechanisms of inorganic ligand substitution reactions and the possibility that such reactions may also play an important role in coenzyme Blz catalyzed reactions. Thus, despite some recent studies which have indicated that changes in the state of axial ligation of cobalamins may not occur during catalysis by some Blz-dependent enzymes, 1, l 2 other work has suggested that such ligation changes may indeed be important in the enzymatic reactions involving B12.13- l7 (1) This project was supported by the National Institutes of Health, U. S . Public Health Service, Grants G M 13,777 (R. G . K.), FR 15 (University of Pennsylvania Medical School Computer Facility), and FR 05415 (University of Pennsylvania School of Medicine). (2) Abbreviations: A-py, 4-aminopyridine; CA-py, 4-carboxamidopyridine (isonicotinamide); CN-py, 4-cyanopyridine; DEA, 2,2dimethoxyethylamine; ME, 2-mercaptoethanol; MEA, 2-methoxyethylamine; Me(D%Hz)HOH, methylaquocobaloxime; Me-py, 4methylpyridine (4-picoline); MPA, 3-methoxypropylamine; PA, propylamine; py, pyridine; TFEA, 2,2,2-trifluoroethylamine. (3) National Science Foundation Predoctoral Fellow, 1968-1971. (4) J. M. Pratt and R. G. Thorp, J . Chem. Soc. A , 187 (1966). ( 5 ) W. C. Randall and R. A. Alberty, Biochemistry, 5,3189 (1966); 6 , 1520 (1967): (6) R. A. Firth, H. A. 0. Hill, J. M. Pratt, R. G . Thorp, and R. J. P. Williams, J . Chem. Soc. A , 2428 (1968). (7) H . A. 0. Hill, J. M. Pratt, R. G. Thorp, B. Ward, and R. J. P. Williams, Biochem. J., 120, 263 (1970). (8) D. Thusius, J . Amer. Chem. Soc., 93, 2629 (1971). (9) Cobaloximes are octahedral cobalt complexes of bis(dimethy1glyoxime). See G. N. Schrauzer, Accounts Chem. Res., 1, 97 (19681, and references cited therein. (10) K . L. Brown and R. G. Kallen, J . Amer. Chem. Soc., 94, 1894 (1972). (11) (a) J . A. Hamilton, R. L. Blakley, F. D. Looney, and M. E. Winfield, Biochim. Biophys. Acta, 177, 374 (1969); (b) J. H. Bayston, F. D. Looney, J . R. Pilbrow, and M. E. Winfield, Biochemistry, 9, 2164 (1970); (c) J. A. Hamilton, R. Yamada, R. L. Blakley, H. P. C. Hogenkamp, F. P. Looney, and M. E. Winfield, ibid., 10, 347 (1971); (d) R. Yamada, Y. Tamao, and R. L . Blakley, ibid., 10, 3959 (1971). (12) P. Y. Law, G. Brown, E. L. Lien, B. M. Babior, and J. M. Wood, ibid., 10, 3428 (1971). (13) W. H . Pailes and H . P. C. Hogenkamp, ibid., 7,4160 (1968). (14) H. P. C. Hogenkamp and S. Holmes, ibid., 9, 1886(1970). (15) H. A. 0. Hill, J. M. Pratt, M. P. O'Riordan, F. R. Williams, and R. J. P. Williams, J . Chem. SOC.A , 1859 (1971).
We wish to report an extension of our earlier studies on the ligation reaction of thiols with methylaquocobaloxime'o to a consideration of two series of nitrogen ligands : primary amines and 4-substituted pyridines (eq 1). This work has considered series of ligands with Me(DzH2)HOH
+L
km
Me(DzH2)L
+ HOH
(I)
kotf
biologically relevant functional groups in an attempt to evaluate the extent of metal-to-ligand T donation in the metal-ligand bond and as a basis for studies of the kinetic trans effect in alkyl cobalt complexes t o be reported separately. Equilibrium constants for the ligation of some amines to methylcobinamide have been reported by others. l 3 Experimental Section Materials. The synthesis of methylaquocobaloxime a n d the handling of solutions thereof have been described elsewhere. l o The free base primary amines, 4-substituted pyridines (py and Me-py), and M E were obtained commercially, redistilled, and stored in the dark under nitrogen a t 4". The hydrochloride of TFEA and the free bases of CN-py, CA-py, and A-py were recrystallized from the appropriate solvent systems and dried in air. Buffer components and inorganic salts were reagent grade and were used without further purification. Solutions of amines and M E were prepared daily and handled as described elsewhere for ME.1o Stock solutions of Me(DzH2)HOH in methanol were used for several successive days and shown to be. stable when protected from exposure t o light by the criterion of spectral stability. Deionized water of greater than 5 X IO6 ohms c m specific resistance was used throughout. ) ligands were Methods. Proton dissociation constants ( ~ K L 'for determined potentiometrically or spectrophotometrically (CN-py, 275 nm) a t 25", ionic strength 1.0 M , maintained with KCI, and titration data were analyzed by a nonlinear least-squares method.18 (16) B. M. Babior, J. B i d . Chem., 245, 6125 (1970). (17) M. K . Essenberg, P. A. Frey, and R. H. Abeles, J . Amer. Chem. Soc., 93, 1242 (1971). (18) R. 0 .Viale and R. G. Kallen, Arch. Biochem. Biophys., 146,271 (1971).
Kaiien, et ai.
1 Reactions of Methylaquocobaloxime with Primary Amines
6698 with 0.1 M borate or potassium phosphate buffers in the same range as in method I. Reactions were initiated by adding a small volume (0.1-0.2 ml) of Me(D2H2)HOH solution in methanol to cuvettes containing buffer, KCI, and ligand in the thermostated cell compartment of a Coleman-Hitachi Model 124 double-beam spectrophotometer maintained at 25.0 i 0.1 (final reaction mixtures were 1.67 % methanol in 3.0-ml total volume). The first-order rate constants (kobsd)were obtained by the method previously described. Second-order rate constants, kanapp, for ligation were obtained from the slopes of graphs of kobsd us. ligand concentration determined by the least-squares method (eq 4). The significant ordinate intercepts on such plots O
k o b s d = konaPPIL]total \ \
0 300
I
,
350
400
'.
I
450
Wavelength
500
S50
Inm)
Figure 1. Spectra of Me(DzH2)H O H ( ) and Me(DLH2)CA-py (--------I. [Complex] = 3.33 X M , [CA-py] = 0.02 M , 0.1 M carbonate buffer, 35% free base, pH 9.65, ionic strength 1.O M . Product formation was 95 % complete. Measurements of pH and recordings of uv and visible spectra were made as described elsewhere. lo The kinetic and thermodynamic constants for the ligation reactions of neutral and anionic methylaquocobaloxime (Scheme I)
koff
(4)
(k,ff), which were generally too small to be accurately determined, indicate incomplete conversion of reactants to products. The values for k,, at two or more p H values were calculated from k,, = konspp/a, where a is the fraction of total amine as the free base, and the agreement among k,, values was within 15 % at worst and usually better than 5%. The ligation rate constant, k,,, for TFEA was calculated from K f (method I ) and k,ff (method IV, below), since recordings of absorbance DS. time for this amine deviated from first order for reasons which are not understood at present. Method 111. Reaction of Me(D2H2)L with M E (Determination of k,, and kerf for the Reaction of Me(D2H2)HOH with L). An alternative method for the determination of k,, and k,ff for the substituted pyridines involved the reaction of Me(D2H2)Lwith M E (eq 5a and 5b). Me(DzHz)L was generated by dissolving sufficient Me(D2H2)kdf
Me(D2Hz)L
I_ Me(D2H2)HOH
+L
(5a)
kOn
Scheme I K'e2
Me(D2Hz)HOH
Me(D2H)HOH-
+ Hi
were determined by the methods described below at ionic strength 1.O M maintained with KCI. Method I. Spectrophotometric Determination of the Equilibrium Constant for Ligation, Kf. The apparent equilibrium constants, Kfapp, for the formation of methylcobaloxime adducts from Me(DzH2)HOHand ligand, L (eq 2), where [Lli,,, is the equilibrium-
ligand concentration distributed over both ionization states, were determined by spectrophotometric measurements of solutions of Me(D2H2)HOH (generally about 5 X M ) at varying ligand concentrations at 440--445 nm (Figure 1). The data at a gioeiz p H were analyzed with a computer by a nonlinear least-squares program based upon eq 3,'s where A0 is the absorbance of Me(D2H2)-
H O H in the absence of added ligand, Ae is the difference between the molar absorptivities of Me(DzH2)HOH and Me(DsH2)L at the wavelength used, and [Me(D2H2)HOHIois the total concentration of cobalt-containing species. The KfaPP values were determined at p H 11.07 for A-py and p H 9.5 for the remaining substituted pyridines; at these p H values the ligand was 2 98 % as the free base and Me(D2H2)HOH was < 2 z ionized, and Kfapp = Kt (Scheme I). A similar condition exists for TFEA at pH 8.5 but for the other primary amines determinations of K p P wererequired at two or more p H values at which the ioniiation of the amines was incomplete (both Me(D2H2)HOH and Me(D2Hz)L were < 2 % ionized). The values of the equilibrium constants for ligation with respect to free base amine were calculated from the relation Kf = Krspp/a (where a is the fraction of total amine as the free base) and the values of Kr thus obtained agreed to within 25% at worst and usually to within 10%.
+
Method 11. Direct Determination of Ligation Rates ( k d For the primary amines, the second-order rate constant for ligation to Me(DzH2)HOH(k,,, Scheme I) was determined from absorbance measurements at 44> nm (Figure 1) obtained under pseudo-firstorder conditions with ligand concentration in at least a tenfold excess over Me(DzH2)HOH concentration. The p H was maintained
Me(DzH2)HOH
+ ME
kME
Me(DzH2)ME
(5b)
k- ME
H O H and L in methanol to give >70% Me(D2H2)Lformation as calculated from the K f values (Table 11). Reaction solutions contained buffer, EDTA'O M ) , KCI, ligand (at a concentration at least tenfold > the final concentration of cobaloxime and sufficiently high to maintain >70% of the complex as the liganded species in the absence of ME), and various concentrations of ME (at least tenfold in excess over the final complex concentration and sufficiently high for >90 % conversion of cobaloxime species to Me(D2H2)ME at equilibrium).l0 Reactions were initiated by the addition of a 20-30-111 aliquot of stock solution of Me(D2H2)L (final concentration of cobalt-containing species 5.0-6.67 X 10-5 M ) to cuvettes containing the reaction mixtures (3.0 ml) situated within the spectrophotometer. Reaction progress was monitored by measuring the increase in absorbance at 325 nm due to the formation of Me(DzH2)ME.lo The dependence of the observed pseudo-first-order rate constants, kobsdrupon the concentrations of M E and L is given by the rate law of eq 6, obtained from eq 5a and
5b by application of the steady-state assumption to the concentration of Me(DZH2)HOHwhen the concentrations of L and ME are in tenfold or greater excess over cobaloxime concentration. The scheme and rate law are similar to those considered by Haim, et a/.,2o for the reactions of C O * ~ ~ ( C N ) ~ H Owith H ~ -various ligands. A plot of the kobsd values os. ME concentration at a constant L concentration describes a rectangular hyperbola (Figure 2) ; the data were analyzed with a computer programla using a nonlinear least-squares method based upon eq 6 to obtain the parameters k,rr and ((kon/k.llE)[L]) (the parameter { ( k , , k - a i ~ / k ~ ~ 1) [ L ] was always too small to be distinguished from zero in the pH region of the present experiments (cf. ref IO)). The values for kvE can be calculated at any pH from the values for kA, k g , and Kt' l o and eq 7, where kA and kB are the rate constants for ligation of
(7) thiol and thiolate anion to Me(D2H2)HOH, respectively, at is the fraction of total M E as the free base, and Kt' is the proton dissocia-
R. G . Kallen. J . Amer. Chem. SOC..93. 6236 (1971). i20) A . J. Haim, R. J. Grassi, and W. K. Wilmarth, Adcan. Chem. Ser., No. 49 (1965). (19)
Journal of the American Chemical Society 1 94:19 1 September 20, 1972
6699 Table I. Equilibrium and Kinetic Constants" for the Axial Ligation of Primary Amines to Me(D2H2)HOH,25", Ionic Strength 1.0 M Constant ~
Trifluoroethylamine
Dimethoxyethylamine
---
Primary amine Methoxyethylamine
Methoxypropylamine
Propylamine
~
~~
~K'L Kr (M-')* k,, (M-' sec-1). k,rr (sec-')C K'r (M-I)' k'", (M-' sec-I)' kforr (sec-'). PK'C-L'
5.68 51.9 4.34d 8.37 x 4.22 2.16 5.13 X lo-' 13.77
8.72 7.89 X lo2 4.79 5.91 x 1 0 - 3 2.39 X 10' 2.04 8.52 X 14.20
9.68 1.74
x
10.33 3.02 x 5.53 2.08 x 1.20 x 4.26 3.55 x 14.08
103
5.22
3.44 x 10-3 5.31 X 10' 3.22 6.06 x 10-2 14.21
10.80 4 25 x 103 7.48 2 07 x 10-3 1 . 5 1 X lo2 6.36 4.21 X 14.13
103 10-3 102 10-2
a See Scheme I for definitions of the constants. * Average of two or more values determined by method I and one value calculated from the average value for k,, (method 11) and k,ff (method IV) and Kr = kon/kori. Average of two or more values determined by method 11. Obtained from method IV. This value was not determined directly but was calculated from k,ff and KI. See Experimental Section. Calculated by method V.
'
0.14
O.I2
1
c
'
t
oOO 002
0 04
0 06
0.08
2 - M e r c o p t o e f h o n o l C o n c e n t r o t i o n (M)
Figure 2. Reactions of methylaquocobaloxime with ligands : determination of k,, and k,fr via reaction of Me(D9H2)Lwith M E (method 111), 25", ionic strength 1.0 M . [Complex] = 6.67 X M . ( O ) , Me(DnHn)Me-py ME, p H 9.55 in 0.1 M carbonate buffer, 35% free base, [Me-py] = 1.50 X M , k o f f = 0.0384 sec-l, ( ( k o n / k n [Me-py]} ~) = 4.95 X lod3M : (A), Me(D2H2)A-py ME, p H 11.05 in 0.1 M phosphate buffer, 29.4% free base, [A-py] = 1.0 X le3 M , kaff = 0.0178 sec-I, ((kan/kei~)[A-py]))= 6.36 X M . The solid lines were calculated from the above parameters obtained by a least-squares method and eq 6.
t
0'04
k
+
+
tion constant for ME. The experiment allows calculation of k,,, k.,ff, and hence Kf for the reaction of the ligand with Me(DzHz)HOH (Scheme I). These experiments were performed at p H values at which the pyridines were >98% as the free base and Me(D2H2)HOHwas 13.5), the
OL
If0
I
I 130
120 I
I
I
140
PH
Figure 3. Proton dissociation constants for Me(D2H2)L: determination of p K f C - by ~ the p H dependence of Me(D2H2)L ligand dissociation rates (method IV), 25", ionic strength 1.0 M . (O), Me(DzH2)py ligand dissociation, final [complex] = 6.67 X M, p K l C - ~= 13.61, k,rt = 0.0546 sec-I, kt0rr = 0.163 sec-'; (A), Me(D2Hz)Me-py ligand dissociation, final [complex] = 5.00 X M , ~K',-L = 13.65, k,rr = 0.0424 sec-I, k'"ff = 0.126 sec-l. The solid lines were calculated using the above parameters obtained by least-squares methods and eq 8.
data were fit to eq 8 with a nonlinear least-squares computer
program's to obtain values for K l c - ~ ,k o f f ,and k',,ff (Scheme I). Such experiments could not be performed for CA-py or CN-py due to the large values of k,tf and the small difference between k,rr and kloff for these ligands, although an approximate value and certainly a lower limit for the value of k'otr for CN-py was determined from the breakdown rate of Me(DeHn)CN-py at pH 13.98. The large Kf value for formation of Me(D2Hn)A-pyrequired dilution of this complex to 8.0 X 10-8 M in order to apply method IV and absorbance measurements were obtained with a Cary Model 14 recording spectrophotometer and 1O-cm path length cells. For A-py the large Kr value made it possible to determine the ~ K ' , - L value from a direct spectrophotometric titration of the liganded complex at sufficiently high concentration of A-py (0.1 M ) that the fraction of methylcobaloxime as the liganded species was >98 % even in strong alkali. The values of k,tf for the primary amines in conjunction with the values of k,,, (method 11) allowed the calculation of another value for Kf (Scheme I; for each amine.
Kallen, et al.
1 Reactions of Methylaquocobaloxime with Primary Amines
6700 Table 11. Equilibrium and Kinetic Constantsn for the Axial Ligation of +Substituted Pyridines to Me(D1H2)HOH, 25", Ionic Strength 1.0 M ~
Constant PK'L Kr ( M-i)b k,, ( M - 1 sec-1)c k , f f (sec-l)d K'r (M-')e k f O n(M-1 sec-l)e k l o f f(sec-i)r pK',-~f
NC2 3 9 2
24 29 X 102 21 x 10' 91 x 10-1
>4 78
x
HzNCO-
3 8 1 1
5 51 2 04 x 1 14 X 5 52 X 2 39 x 3 90 x 1 63 x 13 61
77 03 X 102 17 X 102 56 x 10-1
lO-ig
---
~
~~
4-Substituted pyridine H-
H2N -
CHZ6 36 3 25 x 1 28 X 4 04 X 3 54 x 4 46 X 1 26 x 13 65
103 102 10-2 102 101 10-1
9 40 1 11 x 1 96 x 1 94 x 4 63 X 5 83 x 1 26 x 14 06
103 lo2 102
IO' 10-l
lo* 102 10-2 102 101 10-i
a See Scheme I for definitions of the constants. Average of one value determined by method I and one value calculated from k,,, and kart obtained in a single experiment by method Ill. Average of one value determined by method 111 and one value calculated from the average value for Kf, the average value of k o f f and , k,, = k , f f K f . Average of one value determined by method 111 and one value determined by method IV. e Calculated by method V. Obtained by method IV. An approximate value and certainly a lower limit for k ' < , f ffrom measurements of the rate of dissociation of CN-py from Me(DzHz)CN-py at p H 13.98. Q
I
13.01
PK'Llpand
Figure 4. Dependence of equilibrium constants for ligation with neutral (solid symbols) and anionic (open symbols) methylaquocobaloxime upon the proton dissociation constant ( ~ K ' L for ) the conjugate acid of the ligand, 25", ionic strength 1.0 M . (e),RS-, slope = 0.18 i 0.01; (B, C), X-py, slope = 0.21 f 0.01 for Kf, slope = 0.06 i 0.03 for K't; (A,A), RNHz, slope = 0.38 i. 0.01 for Kf, slope = 0.31 & 0.03 for K'f. The solid lifieswere calculated by a least-squares method. Method V. Calculation of Ktr and kiOn. The K't values were calculated from the relation K'f = K',-LKf/K',, based on the cyclic nature of the equilibria (Scheme I), the data in Tables I and 11, and the value pK',, = 1 2.68.1° Values fork',,, were calculated from the values of k'98% liganded as a consequence of the large values of Kf and K’t for this complex. The two methods provided PK’,-~values of 14.05 and 14.07, respectively. Kinetics of Ligation to Methylaquocobaloxime. The rate constants for ligation to both neutral and anionic methylaquocobaloxime are contained in Table I for the primary amines and in Table I1 for the substituted pyridines. For A-py, Me-py, and py the values of koff determined from direct ligand dissociation experiments (method IV) agreed to within 15% of the values obtained by reaction of Me(D2H2)L with M E (method 111). The dependencies of the rate constants for ligation to neutral methylaquocobaloxime upon the pK’ value of the conjugate acid of the ligand for the primary amines, substituted pyridines, thiolate anions, and neutral thiols10*2z are shown in Figure 6, and while the magnitudes of the ligation rate constants for these series vary by more than 46-fold in the order RNH, < RS- < RSH < X-py, the slopes of the lines are uniformly small ( p < 0.1). The rate constants k‘on for ligation to anionic methylaquocobaloxime are smaller than k,, for both the amines and the pyridines (thiolate anions show no significant reaction with anionic methylaquocobaloxime ‘0) and the dependencies of k’on upon the pK’ value of the conjugate acid of the ligand yield p values of less than 0.1 (Figure 6). The amine ligands dissociate in general more slowly than do the pyridines from both the neutral and anionic complexes and the dependencies of the rate constants for ligand dissociation upon the pK‘ value of the conjugate (22) While the values of the proton dissociation constants for the conjugate acids of neutral thiols have not been measured, they have been estimated to occur at H O -6.23 For simplicity the rate constants for the reaction of RSH with Me(D2H2)HOH have been plotted cs. the pK’ for RSH. (23) E. M. Arnett, Progr. Phys. Org. Chem., 1, 223 (1963). N
Figure 7. Dependence of the ligand dissociation rate constants from neutral (solid symbols) and anionic (open symbols) Me(D2Hz)L upon the proton dissociation constant ( ~ K L ’of) the conjugate acid of the ligand, 25”, ionic strength 1.0 M . (m, E), X-py, slope = -0.17 & 0.02 for k,ff, slope = -0.08 =k 0.03 for k’,ft; (A,A), RNHz, slope = -0.33 i- 0.02 for koff,slope = -0.23 2~ 0.02 for k’aff. The solid lines were calculated by a least-squares method.
acid of the ligand are quite different ( p = -0.33 st 0.02 for RNH2, p = -0.17 f 0.02 for X-py for kotf; p = -0.23 f 0.02 for RNH,, and p = -0.08 f 0.03 for X-py for k’,tf, Figure 7). Discussion Ligation Equilibria of Methylaquocobaloxime. A soft or class b character has been assigned to Mevitamin (D2H2)HOH, cobaloximes and methylcobalt corrinsZ7 and is consistent with the observed greater ligand affinity of soft thiolate anions than the hard primary a m i n e ~ ~ ~ toj ~Me(D2Hz)HOH 9 (Figure 4). In contrast, most Co(II1) complexes (e.g., C O ” ‘ ( N H ~ ) ~ H O H ~etc.) + , are hard acids2* with the interesting exceptions of the soft acids, Co(CN)jHOH2- and C O ( N H ~ ) ~ S O + below). It thus 3 l ~(see appears that the presence of one or more soft or unsaturated ligands is sufficient to confer the characteristic of softness to a cobalt complex. Furthermore, softness appears to be directly related to the ability of a cobalt complex to stabilize a carbon-cobalt bond as seen in the cobaloximes, the cobalt corrins, and even pentacyanocobaltate(III), the alkyl derivatives of which have been prepared by Halpern and Maher.32 The concept of metal-to-ligand A bonding will be invoked to explain both the order of strength of ligation (RNHz < X-py < RS-) and the reverse order for the dependence of ligation strength upon ligand basicity (Figure 4). The order of Me(DZH2)L stability is attrib(IIQZ5lz6
(24) A. L. Crumbliss and W. K . Wilmarth, J . Amer. Chem. Soc., 92, 2593 (1970). (25) D. N. Hague and J. Halpern, Inorg. Chem., 6 , 2059 (1967). (26) H. G. Tsiang and W. K. Wilmarth, ibid.,7, 2535 (1968). (27) H. A. 0. Hill, J. M. Pratt, and R. J . P. Williams, Chem. Erit., 5, 156 (1969). (28) F. Basolo and R. G. Pearson. “Mechanism of Inorganic Reactions,” 2nd ed, Wiley, New York, N. Y., 1967, pp 23-31. (29) W. P. Jencks, “Catalysis in Chemistry and Enzymology,” McGraw-Hill, New York, N. Y., 1969, pp 89-92. (30) Reference 28, p 206. (31) J. Halpern, R. A. Palmer, and L. M. Blakley, J . Amer. Chem. Soc., 88, 2877 (1966). (32) J. Halpern and J. P. Maher, ibid., 86, 2311 (1964); 87, 5361 (1965).
Kallen, et al. / Reactions of Methylaquocobaloxime with Primary Amines
6702
uted to the ability of thiols to accept electrons into account for the large differences in the stabilities of the relatively low-lying unfilled d orbitals while pyridines liganded complexes Me(D2H2)Lwhen related to basicity accept electrons into higher energy unfilled a*-anti(Figure 4). bonding orbitals ; 3 4 primary amines cannot accept The equilibrium constants for ligation to anionic electrons in either fashion. This ligand stability order methylaquocobaloxime (K’f) are significantly lower is the same as the order previously established for the than those for binding to the neutral complex (Figure 4). trans direction of substituents into the square-planar The increased electron density on the cobalt atom complexes of Pt35 and for the stabililization of lowupon loss of a proton from neutral Me(D2H2)HOHto valence states of numerous transition metals, 36 proform an anionic complex apparently decreases the cesses which have been related to the a-accepting effectiveness of ligand electron donation and hence ability of the ligands. The reverse order for the debonding to cobalt. The significantly lesser dependence pendence, p, of Me(D2H2)Lstability on ligand basicity of ligation affinity to anionic methylaquocobaloxime among the three series of ligands ( p = 0.18, 0.21, and upon the pK’ value for the conjugate acid of the ligand 0.38, for thiolate anions, substituted pyridines, and for the pyridines ( p = 0.06 f 0.03), the limited data primary amines, respectively) is not unexpected based notwithstanding, as compared to the primary amines on the following considerations: (i) an increase in ( p = 0.31 f 0.03) may be yet another indication of the basicity is associated with an increased ability for u importance of metal-to-ligand a donation. Thus, an donation for all ligands (note especially the greater deincrease in electron density on the cobalt atom (upon pendence of Me(D2H2)Lstability on ligand basicity for ionization to form the anionic conjugate base) would the primary amines which are solely u donors); (ii) an be expected to increase the effectiveness of such a increase in basicity is associated with a decreased donation. This effect may then be responsible for the ability for the X-py and thiolate anion ligands to funcgreater difference in p values for the pyridines (A@ = tion as a acceptors (thus, as a bonding becomes in0.21 - 0.06 = 0.15) compared with the aliphatic creasingly important, progressively lesser dependencies amines (Ap = 0.38 - 0.31 = 0.07) for the dependence of Me(DeH2)L stability upon ligand basicity are obof the ligation equilibria on the pK’ of the conjugate served). acid of the ligand for the neutral and anionic complexes Metal-to-ligand a bonding (i) has been firmly estab( K f us. K ’ f , Figure 4). lished in a number of transition metal c o m p l e x e ~ , ~ ~ - ~Kinetics ~ and Mechanism of Ligation to Me(D2H2)(ii) has been invoked for the cobalt corrins in 1 0 ~ ~ 0HOH. The rate constants for ligation (k,,, Tables I oxidation states, for the alkylcobalt corrins,14 for the and I1 and Figure 6 ) indicate that Me(D2H2)HOHis exligation of pyridines to c o b a l ~ x i m e s ( I I I ) and , ~ ~ for the ceedingly reactive compared to ordinary Co(II1) comligation of various ligands to methylcobaloxime in nonp l e ~ e s ~ ’and - ~ ~the majority of cobaloximes(III), e.g., aqueous solvents,42and (iii) is well substantiated in the Co(D2H2) (N02)HOH, etc. 25 Methylaquocobaloxime complexes of olefins with c o b a l o x i m e ~ ( 1 and ) ~ ~in ~ ~the ~ is, however, not as reactive as a q u ~ c o b a l a m i n(by ~~~ complexes of CO, CH3CN, CH3NC with methylcobalabout an order of magnitude) and is only slightly more oxime. 45 reactive than sulfitoaquocobaloxime, Co(D2H2)(S03)HOH-.26 Metal-to-ligand a bonding in the transition state has been invoked previously in order to explain the inIn comparisons between the alkylcobalt complexes creased reactivity of neutral thiol over thiolate anionlo and the usual Co(II1) complexes there are 104-105 inin the ligation reactions of Me(D2H2)HOH. The prescreases in the rates of ligation (present data and ref 24, ent evidence implicates significant contributions of this cf. ref 25) and substantial differences in the fraction of type of bonding in the ground state as well. An argutotal complex as the pentacoordinate species (ref 50, cf. ment outlined by Jencks, 46 who has discounted the ref 48). These marked differences suggest that the possibility that large differences in nucleophilicity when common practice of considering alkylcobalt complexes related to basicity can be attributed to differences in to be Co(II1) complexes with carbanion ligands is insolvation of the nucleophile, can be extended such that appropriate and very probably mi~leading.5~ differences in solvation of the ligands are unlikely to The small dependence of k,, upon ligand basicity (Figure 6 ) within each series of ligands ( p values
