h l a y 5 , 1957
ASSOCIATION OF 4-METHYLIMIDAZOLE WITH c U ( r 1 )
sociation constants. Indeed, Azzari and K r a u P have shown recently that the Bjerrum equation fails completely in solutions of higher dielectric constant. Acknowledgments.-The authors are indebted to Dr. C. A. Kraus of Brown University for suggesting this research topic and for valuable discussions and I (35) M. Azzari and C. A. Kraus, Proc. Nafl. Acod. Sci., 42, 590 (1956).
[CONTRIBUTION FROM
THE
AND
ZN(I1) IONS
2 123
advice. Thanks are also due to Professor Robert H. Cole of Brown University for the use of his apparatus to measure dielectric constants of the solvent mixtures. Appreciation is expressed for solvents to The Dow Chemical Company for ethylene chloride, and the Calco Chemical Company for nitrobenzene. WORCESTER, MASS.
BIOLOGICAL LABORATORIES, HARVARD UNIVERSITY, AND CHEMISTRY, HARVARD MEDICAL SCHOOL]
THE
DEPARTMENT OF BIOLOGICAL
The Association of 4-Methylimidazole with the Ions of Cupric Copper and Zinc; with Some Observations an 2,4-Dimethylimidazole B Y Y.4SUHlKO NOZAKI,~ FRANK R. N. CURD, RAYMOND F. CHENAND
JOHX
T. EDSALI,2.3
RECEIVED DECEMBER 7, 1956 The 4-methyl and the 2,4-dimethyl derivatives of imidazole have been studied in their interactions with hydrogen, cupric and zinc ions, a t different temperatures. The pH titrations, in the absence of Cu or Zn ions, gave pK' values which were extrapolated to zero ionic strength. Heats of reaction and standard entropies associated with these pK values were also 0.7 kcal./mole and AS" in the range -6.5 i 0.8 cal. deg.-l mole-'.) Similar determined. ( A H " is in the range 8.5 titrations, in the presence of Cu(I1) and Zn(II), showed that the number of molecules of both imidazolederivatives, bound to either of these ions, approached an upper limit of 4, a t high imidazole concentrations. This number is the same as for unsubstituted imidazole. The intrinsic association constants log ~ , (=i 1,2,3,4) a t 25' were found for 4-methylimidazole to be 3.53, 3.31, 3.05 and 2.56, respectively, for combination with C u ( I I ) , and 1.84, 2.35, 2.82 and 2.98 for combination with Zn(I1). Approximate values for AH' in the combination of 4-methylimidazole with these ions have been estimated. Incomplete studies on the binding of 2,4-dimethylimidazole t o copper indicated association constants of the same order of magnitude, but somewhat smaller, than those for 4-rnethylimidazole. A discussion is given of the stereochemistry of the copper and zinc complexes, and of some of the structural implications of the observed association constants.
*
The reactivity of the imidazole group of the histidy1 residue in proteins has assumed great importance for the understanding of interactions between proteins and several metallic ion^.^-^ A previous report described the application of a method suggested by Scatchard to the interpretation of the equilibria between the parent imidazole and Cu(I1) and Zn(I1) ions.' A similar study has now been made of the corresponding equilibria of the 4-methyl derivative of imidazole, chosen because it is substituted in the same position as the imidazole ring in the histidyl residue, and thus represents a step toward the study of the metal-binding behavior of the histidyl residue in peptide chains. A fragmentary study has also been made of 2,4-dimethylimidazole, in order to determine whether the additional methyl group, attached to the carbon atom between the two nitrogens of the imidazole ring, would significantly alter the binding of the imidazole molecule to the metallic ions. (1) Overseas Research Fellow, sponsored by the Japanese Government under exchange Visitor Program a t Harvard University, 19541955. (2) Support for this research was provided by a grant to John T. Edsall (NSF-G621) from the National Science Foundation, and by a special fellowship granted t o him by the John Simon Guggenheim Memorial Foundation. (3) Requests for reprints and inquiries concerning this paper should be addressed to Dr. J. T. Edsall, Biological Laboratories, Harvard University, Cambridge 38, Massachusetts. (4) F. R . N. Gurd and D. S. Goodman, THISJOURNAL, 74, 670 ( 1952). (5) C. Tanford, ibid., 74, 211 (1962). ( 0 ) F. R. N.Gurd and P. E. Wilcox, Advances in Profcin C h o n . , 11, 311 (1956). (7) J . T . Edsall. 0. Felaenfeld, D. S. Goodman and F. R . N. Gurd, THXS J O U R N A L . 76, 3054 (1954).
Materials and Methods 4-Methylimidazole was prepared as the crystalline salt, 4-methylimidazolium nitrate, by a modification of the method of Weidenhagen and He.rrmann.8 The free base was prepared, in the manner described by them, from acetol acetate, aqueous ammonia and formaldehyde in the presence of cupric acetate. The resulting copper complex of 4methylimidazole was deconiposed, and the copper precipitated as sulfide, by treatment with hydrogen sulfide a t 50". After removal of the precipitate, and cooling, dilute nitric acid was added cautiously to the solution, with constant stirring, until a pH between 2 and 3 was attained. (Further addition of nitric acid decreases both the yield and the purity of the product.) The solution was concentrated by evaporation to a small volume, in vucuo a t 45-55', filtered with charcoal and dried in a desiccator. The resulting crude product was recrystallized two or three times from acetone. The material was colorless and melted a t 110.5111.5'. DedichenD reported a melting point of 110". The purity of the material obtained by us was confirmed also by the constancy of the value of pK' obtained in the pH titrations (see below) for widely varying ratios of the concentration of free base to that of the conjugate imidazolium ion. 2,4-Dimethylimidazole also was prepared by the method of Weidenhagen and Herrmann*; the base released on removal of Cu(1) by sulfide was converted directly to the nitrate and the product was obtained by evaporation to dryness a t low temperature. Recrystallization was from acetone or acetone-ether mixtures. Thrice recrystallized 2,4-dimethylimidazolium nitrate melted a t 133-134". The purity of the product was confirmed by the p H titrations discussed below. The preparation of mixtures of methylimidazolium nitrates and Cu(1I) or Zn(I1) nitrates and their titration with NaOH were carried out as previously described.' The pH of each mixture was determined with a Beckman (8) R . Weidenhagen and R. Herrmanu, Ber., 68, 1953 (1935). See aim K. Hofmann. "Imidazole and its Derivatives" Part I , Interscience Publishers, Inc., N e w York,N . Y.,1953, Chapter 11. (9) G. Dedichen, Bn.,39, 1831 (1906).
2124
Y. NOZAKI,F. R. AT. GURD,R. F. CHENAND J. T. EDSALL
Model G p H meter, first a t 2.5" in a cold room and again a t laboratory temperature. The instrument and solutions were allowed to reach temperature equilibrium for several hours before readings were taken. Measurements were repeated at five-minute intervals and care was taken t o maintain the precision of the measurements at h 0 . 0 1 p H unit. The buffer described by Bates and .4cree'0 containing 0.02M KHxPOd, 0.03M NagHPO, and 0.02M KaCl was used for calibration. The PH values assigned to this buffer a t various temperatures were obtained by interpolation in Table I1 of the publication of Bates and Xcree.'o
Vol. 79
than those which usually have been assumed as typical for imidazole groups.I3 The standard entropy of ionization is in all cases negative and of the In attempting to order of -6 cal. deg.-hole-'. interpret these values, we note that the process involved is the transfer of a proton from an imidazolium ion to a water molecule to form an H 3 0 f ion. Both the imidazolium ion and the H30+ion tend to attract and orient water molecules, with an ac-
Results TABLE 11 Dissociation of Hydrogen Ions.-Table I shows the pK' values for the dissociation of $-methylhid- THERMODYNAMIC V A L U E S FOR I"E 1IYDROGEN I O N E Q U I azole and of 2,4-dimethylimidazole. The values LIBRIA OF VARIOUSIXIDAZOLES AT 25" for the former were obtained a t 2.5 and 29", and &SO, AF'. All0, cal. for the latter a t 4 and 22". Interpolated or extrapkcal./ kcal./ deg.-* Conjugate acid of p K a t I'/S = 0 mole mole mole-' olated PK' values are given a t 25". Solutions were made up to 0.021U in total imidazole derivative Imidazole 6 . 9 5 ' t ; t i . 9 7 b f 9 . 5 +T,7J - 6 . i J and the ionic strength adjusted with sodium ni- 1-?rlethyliinidaziile 7 .OR" + 9.6 trate. The titration of 4-methylimidazole was 2-Methylimidazole 7.86'' +lo.; carried out, a t each ionic strength and temperature, 4-Meth)ilimidazole 7.52"; T .54" + 10.3 +8.6 - 5 . 7 for seven different ratios of imidazolium ion to free 2,i-Dimethylbase, ranging from 6 to 0.17. The calculated pK' imidazole 8.36"; 8.38d + 1 1 . 4 f 9 . 2 -7.4 values for the seven solutions agreed within *0.01, 2,4,5-Trimethylexcept occasionally a t the extreme ends of the imidazole 8.92" +12.2 curve, where the deviation was sometimes twice as a A . H . h l . Kirby and A . Neuberger, Biochenz. J . , 32, great. The titrations of 2,4-dimethylimidazole 1146 (1938). * J . T. Edsall, G. Felsenfeld, D. S. Goodman and F. R. N. Gurd, THISJOURNAL, 76,3054 (1954). N. C. are somewhat less accurate, with a probable error Li, J. M. White and E. Doody, ibid., 76, 6219 (1954). of perhaps 0.025 in the reported pK' values. d Present investigation. R . b'. Cowgill and W. M . The results are given for several different ionic Clark, J . Biol. Chem., 198, 33 (1962), give a pK' for this strengths (r/2) and are extrapolated to zero ionic substance of 8.86 in 23.3% ethanol a t 30" and ionic strength strength according to a simplified version of the 0.2. Following their calculation, we have taken the value in water, a t 25' and zero ionic strength, as 0.06 greater than Debye-Huckel equation previously employed by this. f I n reference 6, the value of AH" for imidazole was Kirby and Xeuberger." given incorrectly as 6.0 kcal./mole. The value listed here is based on the data given in that reference, and the calculap K = PK' - 0.5~'?72/(1 + dE2j tion has been corrected. Values for AH' and AS' are The results of the present study are compared based on temperature coefficients of pK values determined in Table I1 with their measurements, in which the in the present investigation, or in reference b above. hydrogen electrode was used. The results agree companying entropy decrease, around a positively within experimental error.I2 charged center, but the orientation around the positively charged imidazolium nitrogen will be TABLE 1 APPAREST DISSOCIATIONCOXSTAXTS, p K ' , AT VARIOUS obstructed to some extent by the adjoining atoms of the ring; whereas no such obstruction exists TEMPERATURES AND IONIC STRENGTHS FOR T H E CONJGGATE around the H 3 0 +ion. Hence a moderate negative ACIDS OF m o IMIDAZOLE BASES value of A S " is to be expected for a proton transfer T e m p . "C. Ionic strength 2.5 29' 25 of this type.I4 4-?\.lethyliniidazoliumion Association of Cu(I1) and Zn(I1) with 4-Methylimidazole.-The results of the titration of mixtures 7.00 i.69 0.16 8.20 of 4-methylimidazole with Cu(NO3)2 and Zn(T\;03)? 7.56 7.63 ,076 8.17 are summarized in Tables I11 and IV. Throughout 7.55 7.64 ,034 8.15 these measurements the ionic strength was main7.46 7 . 33 . 00 8.00 tained a t 0.15-0.16. The first three columns in 2,4-Uitnetli~-liniidazoliutnion 'fable 111, and the subhead and first column of 4 22 25 'fable IV, define the compositions of the mixtures; 0 . lii 9.05 8.59 8.52 the next three columns show the results a t 2.5'; 0,OO 8.91 8.45 8.38 and the last three show the results a t 20 and E o , The values of A H o in Table I1 range from 7.7 to respectively. The concentration of the imidazole ! I 2 kcal./mole. These values are somewhat larger derivative in the free base form is expressed as its negative logarithm, PA,and the average number of (10) R. G. Bates a n d S. F. Acree, J . Research N a i l . Bur. Standards, 4-methylimidazole molecules bound per metal ion is 30, 129 (1943). denoted by ii. The values of p-4 and ii were ob(11) A. H. M . Kirby and A . r\-euberger, Biochcm. J . , 33, 1146 (1938). Concerning t h e extrapolation of pK' values to zero ionic tained from the data by the method previously emstrength, see also 4 . S e u b e r g e r , Pvoc. R o y . Soc. !London), A158, G8 ployed with i m i d a ~ o l e . ~
*
(1937). ( 1 2 ) Much of t h e difference of a b o u t 0 02 unit m a y be due in a n y case to differences in methods of stahdardization. See also R . G. Hates, "Electrometric pH Determinations," John Wiley and Sons, Inc.. h-ew York, PIT. Y.,1954, Chap. 4
(13) E. J. Cohn a n d J. T. Gdsall, "Proteins, Amino Acids a n d Pcp tides," Reinhold Publ. Corp., New York. N. Y . , 1943, Chapters 4 a n d 5 (14) Compare t h e discussion by E. J. King a n d G. TV King, THIS J O U R N A L , 78, 1089 (19561, especially pp. 1095-1098.
2125
ASSOCIATION O F 4-METHYLIMIDAZOLE WITH CU(I1) AND z N ( / I ) IONS
M a y 5 , 1957
TABLE I11 TITRATION O F MIXTURES OF 4-METHYLIMIDAZOLIUM NITRATE (4-MeIrn+NO3-) AND CUPRICNITRATE Total molar concn. of
4MeIm+-
Results a t 2.5O
pK'
Cu(Nod2 NaOH 0.0113 0.002377 ,0113 ,004754 .007131 ,0113 ,009508 ,0113 ,01664 ,0113 ,0113 .02377 ,0113 ,03090 ,04041 ,0113 ,04754 ,0113 .05705 ,0113 .007132 .0214 .007132 ,0136 ,02377 .0600" ,0186 ,0186 ,03090 .0600a .03090 .0600n .0135 ,04754 .0600u ,0186
NOa0,1354 ,1354 ,1354 ,1354 ,1354 ,1354 ,1354 ,1354 ,1354 ,1354 .0200n .0300°
pH 3.93 4.28 4.50 4.72 5.25 5.70 fi.lfi 6.76 7.13 7.48 5.15 5.18 5.62 5.99 6.39 6.96
= 8.20 PA i 5.15 0.21 4.80 0.42 4.59 0.63 4 . 3 8 0.84 3.88 1.46 3.45 2.08 3.02 2.65 2.46 3.27 2.13 3.55 1.83 3.73 4.94 0.32 4.66 0.52 4 . 0 2 1.27 3.75 1.65 3.35 2.25 3.14 2.52
I 1
Result a t 29' p K ' = 7.60-
pH
3.82 4.16 4.39 4.58 5.09 5.48 5.90 6.38 6.65 6.95 5.00 5.02 5.44 5.80 6.15 6.72
$A 4.66 4.32 4.10 3.92 3.44 3.07 2.68 2.24 2.01 1.76 4.49 4.22 3.60 3.34 2.99 2.79
i
v
0.21 0.42 0.62 0.83 1.44 2.03 2.55 3.08 3.34 3.50 0.33 0.52 1.27 1.64 2.21 2.41
2.6 I
XaNO, added to bring total ionic strength to 0.15-0.16. The symbol PA, here and elsewhere in this paper, denotes the negative logarithm of the concentration of free basic imidazole. 0
TABLE IV MIXTURES O F 4-klETHYLIMIDAZOLIUM XI(4-MeIm +Koa-) AXD ZINC NITRATE Total molar concentration of 4-MeI1n~h-O~was 0.1354 and that of Zn(N03)g was 0.0111 in all solutions reported here. Resqlts a t 2.5' Results a t 27O Total N a O H pK 8.20 PK' = 7.64 -
TITRATION OF TRATE
5
added (mole/l.)
pH
$A
0,001418 ,002836 ,005138 ,01028 ,01541 ,02055 ,02569 ,03084 ,03597 ,04614 ,06166
5.43 5.70 5.90 6.13 6.26 6.38 6.48 6.60 6.74 7.08 7.61
3.64 3.38 3.19 2.93 2.86 2.76 2.68 2.58 2.46 2.17 1.72
pH
$A
5.01 5.28 5.50 5,.74 5.88 6.00 6.10 6.20 6.33 6.62 7.07
3.50 3.24 3.03 2.80 2.68 2.58 2.50 2.42 2.31 2.07 1.72
Y
0.11 .22 .40 .83 1.27 1.69 2.13 2.54 2.93 3.55 3.85
Y
0.10 .20 .38 .78 1.20 1.61 2.03 2.44 2.80 3.39 3.77
From the data in Tables I11 and IV plots of 5 against PA (Bjerrum's "formation function") may be constructed. The curves so formed are nearly symmetrical about F = 2, and it appears reasonable to assume that i j approaches a limiting value of 4 a t high concentrations of free 4-methylimidazole. The justification for this assumption lies partly in the approximate symmetry about i j = 2, referred to above, and partly in the extensive evidence that coordination complexes of Cu(I1) and Zn(I1) with nitrogenous bases generally approach a i j value of 4. Similar conclusions concerning the Cu(I1)-imidazole system' have been confirmed by the polarographic technique. The data in Tables I11 and I V have been analyzed by the method of Scatchard' from plots of log Q versus i j where Q = t/(4
- t )(A)
(1)
These plots are shown in Figs. 1 and 2, derived from the data of Tables I11 and I V , respectively. The open circles represent points observed a t 29 and 27', respectively, and the closed circles a t 2.5'. The (15) N. C. I,i, J . hl. White and E. Doody, THIS JOURNAL, 76, 6219 (1954).
0
I
2
-
3.
3
4
Fig. 1.-Values of the Scatchard function log Q for the binding of Cu(I1) to 4-rnethylirnidazole as a function of the mean number ( i ) of imidazole molecules bound per Cu ion: upper curve data at 2 . 5 ' ; lower curve data at 29". Increased probable error of the data a t high i; values is indicated by the increased height of the rectangles on the right-hand side of the curves. Circles and rectangles are experimental values; curves are drawn on the basis of the constants listed in Table XT. 3.4 1
I
I
I
3*21 3.0
2.8
6
2.6
I
0
_"
I
2.4 2.2 2.0
0
I
I
I
2
I
-
3.
3
i 4
Fig. 2.-Log Q for the binding of Zn(l1) t o 4-methylimidazole. The data should be compared with those for Cu(I1) in Fig. 1 : upper curve data a t 2 . 5 " ; lower curve data a t 27'.
circles are drawn to represent the probable accuracy with which log Q is measured. Errors in the pH measurements affect most directly the value of (A) in equation 1. The computed valCle of (A) depends both on the measurement of the fiH in the experimental mixture and on the value of pk" determined separately. Taking the precision of both values as *0.01 unit, the uncertainty in the value
2126
Y. Noz.ixr, F.R.S . (\.URD, K.F'. CHENAND
of log 0may- be expected to be 10.02 unit throughout most of the range of conditions studied. 'The circles in the figures rather overestimate the UT?certainties in the values of P, As z; approachs $, errors in (A) begin to affect the value of ti nicch more sharply, and in turn the cornl,utcition 01 beconics abruptly subject to iarge errors. ?he rcc tangles in Figs. 1 and 2 show the iiiaxiniuin limtls of the parameters nhen PK' and the fiH inexm:nient are both ascribed errors cjf + 0 01 unit If we accept the assumption that thc ina fiinciin value of ti is 4, the relation of ti to ('21 n u y be defined' in terms of four successive association constants, k?, ke, k, and k,
(2.)
instead of the k values, it is often illuminating to express the results in terins of the "intrinsic association constants," K I , K Z , K 3 and K 4 , which are defined by the relations KI
3
kl/4;
~2
= 2k&;
~3
=
:3k3,~'2;~4 = 4k4
(3)
The factors Il'd, 2/3, s,/2 and 4 in ( 3 ) art' statistical factors. For a system in which all the ligand sites are equivalent and also react independently with the ligand, all the four K values would be identical. In the systems studied here, this is far from being the case, and the differences in the successive I; values give a measure of the character of the interactions in the binding of the ligaild 1i1olecules. A; previously s h o ~ 1 1 the , ~ value of log K ! is equal t the limiting value of log Q .rs-he!i 5 approach,'as zeria. and the value of log ~4 is e y u d to the limiting \--I ' 4 u: of log Q when ti approaches the xnaxiinarn value of 2. The values of log K: and leg ~3 iii:i!: also be poixi-. puted froin such data as those sh(>::-n in Figs. 1 arid 2, as previously described. The Fz and K values are constants for a given ionic stwigth and temperature; the values in Tables 1' aiid 1-1 below r d c r specifically to ionic strength 0.16. TASLZV CALCULATED I N T R I S S I C tk3SOCI.4TlOS COSSTASTS F')R ASD
LOg K i Lug K? Log KZ Log K ,
zn"
--
1
I
/
Discussion The results of the present study with 4-methylimidazole shorn the same striking contrast in behavior between Cu(I1) and Zn(I1) as was found in the study with unsubstituted imidazoleP I n both cases the imidazole compound shows increasing affinity for Zn(II) as the degree of complex formation increases; in other words there are "positive interactions" between the coordinated imidazole groups. With Cu(I1) the opposite behavior is seen and the interactions are negative. This contrasting behavior appears to be the rule with all the simple imidazoles that have been tested, including the 1-methyl derivative, and is indeed characteristic of the behavior of other systems in which nitrogen is the donor atom of the ligand m ~ l e c u l e . ~ A consequence of the contrasting behavior with Cu(I1) and with Zn(I1) is illustrated in Figs. 3 and 4 which show the per cent. of each metal ion in each complex as a function of the concentration of the free base 4-methylimidazole. The curves were computed from the k values for 29 and 27' corresponding to the K values given in Table V. The conversion from K values to k values was made according to equation 3. Noteworthy is the much greater overlapping of the regions of existence of the Zn(I1) complexes. Indeed the Zn(II) system moves from 50% in the form of the uncomplexed ion to 50% in the form of the quaternary complex when the concentration of the uncombined base is increased about fivefold. By contrast the corresponding change in the Cu(I1) system requires an increase of approximately 200-fold. (10) Further details concerning the work on 2,4-dlmethylimidazole are given in the Honors Thesis of Raymond F Chen, submitted to rhc Board of Tutors in Biochemical Sciences, Hatvard University, 1955
-log [ 4 - Methylimidazole]-
Fig. 4.-The relative concentrations of Zn(I1) and its complexes with 4-rnethyiirnidazole, plotted in the same manner as the data of Fig. 3.
The successive log h values for the association of Cu(I1) with four different imidazole derivatives and of Zn(I1) with two of them are brought together in Table VI. For the sake of comparison TABLE VI SUCCESSIVE ASSOCIATIONCOXSTANTSFOR Cu(I1) Zn( 11) WITH SOMEIMIDAZOLES' Log k values for ionic strength 0.15-0.16 and 25' Irnidazole6
Cu(I1) complexes 14Methylimidazole
Methylirnidazolec
2,4-Dimethylimidazole
AND
Zn(I1) complexes 4-
Imidazole6
hlethylimidazole
Log ki 4.33 4.22 4.13 3.8 2.57 2.44 Log kz 3.54 3.54 3.49 2.36 2.53 Log ka 2.82 2.89 2.87 2.22 2.64 L O g h 2.03 2.21 1.96 2.01 2.38 Xote that the values given in this table are log k values as defined by equation 2. They are related by equation 3 to the log K values given in Table V. J . T. Edsall, G. Felsenfeld, D. S. Goodman and F. R . N. Gurd, THIS JOURNAL, 76, 3054 (1954). N. C. Li, J . hl. White and E. Doody, ibid., 76,6219 (1954).
the values are extrapolated or interpolated to correspond with 25' and in each case the ionic strength i s 0.15-0.16.
1'.h T 0 z ~ ~F. 1 ,R.N. GURD,R. F. CHENAND J. T. EDSALL
2128
Comparison of the trend of the values of log kl for the 1 : 1 Cu(I1) complexes in Table VI with the trend of the fiK values listed in Table I1 shows that the order of decreasing affinity for Cu(I1) is the same as that of increasing affinity for hydrogen ion. The decreasing trend of the values for Cu(I1) is considerably gentler than the increasing trend for hydrogen ions. The contrasting picture is considerably accented if we broaden the comparison to include ammonia which behaves much like the imidazole derivatives with respect to Cu(I1) but falls beyond trimethylimidazole with respect to hydrogen ion.6 The absence of a strong trend in affinity for Cu(I1) paralleling the basicity of the imidazole derivative might be taken as an indication not that no such underlying tendency exists, but that it is obscured by the effects of steric hindrance operating in the opposite sense. However, if steric hindrance were such a powerful factor in the formation of the 1 : 1 complexes we should expect that far larger effects would be evident in the formation of the higher Cu(I1) complexes containing two, three or four ligand molecules crowded around the central metal atom. No such trend is evident in Table TI. Cowgill and Clark20 have studied the effect of substitution on the tendency of imidazoles to coordinate with Fe(II1) in ferrimesoporphyrin. The coordination appeared to be strongly inhibited in those derivatives such as 2-methylimidazole and 4,5-dimethylimidazole in which both nitrogen atoms are adjacent to a carbon atom that carries a substituent. On the other hand, derivatives in which one nitrogen atom is not so hindered were shown to combine readily with the porphyrin. Presumably 4-methylimidazole is in this category, although it was not studied by Cowgill and Clark; it 11-odd coordinate a t the nitrogen atom in position y
137
2
7
1
0.99 -H
i
C ,//
V
Fig. j.-Diagram of the steric relations of two imidazole rings and a water molecule, coordinated around a central Cu ion. The Cu-K bonds and the Cu-0 bond are assumed to be 2.0 A . long. In the drawing all these bonds are assumed coplanar. The dotted arcs of circles on the upper left indicate the overlapping van der Waals radii of the hydrogen atoms on two adjoining imidazole rings. A slight overlapping is also shown to exist between the van der Waals radii of the hydrogen atoms of the attached water molecule on the right and the neighboring imidazole ring (see text). (20) R .W.Cowgill a n d 11'. M. Clark, J Biol C h e m . , 198,33 (1952)
17(Jl.7 ; )
1 (in the alternative numbering system these positions would be 5 and 3 , respectively), and so on. Possibly there is some tendency for similar preferences in the coordination of imidazole derivatives with free metal ions. The analogy should not lie carried far, however, because Cowgill and Clark also showed that among those imidazole dcrivatives that were effective in forming coinp1e:tes there was a geiieral tendency for the strength o f coordination to increase with incrensing pk", ;iii effect opposite to that found in the present study. Some further comments on the stereochemistry of these complexes may be offered. In general, tetra-coordinated zinc complexes are tetrahedral. while those of copper are generally planar6>*lbut may sometimes correspond to a more or less distorted tetrahedron. The strongly positive interactions which are apparent in the binding of many organic bases to the Zn(I1) ion are present to about the same extent in imidazole and 4-methylimidazole; the extra methyl group apparently produces no added hindrance to the binding of the successive imidazole molecules to the zinc ion. This appears not unreasonable if the methyl groups in the complex are oriented outward, away from the nitrogen which is attached to the copper, which must then be the nitrogen in position 1. On the other hand if the Cu(1I) complexes are square and planar, some difficult steric problems arise, in the placing of three or four imidazole rings about a central cupric ion. Jhre take the Cu-N distance as approximately 2.0 A., which appears reasonable in the light of available data.?? In constructing a model for the imidazole ring, the detailed X-ray diffraction study by Donohue, Lavine and RollettZ3of histidine hydrochloride monohydrate gives by far the most definite information available. The imidazole ring in this crystal is in the positively charged (imidazolium) form. The Cu(I1) imidazole complexes should be fairly closely similar in electron distribution because of the positive charge on the copper (basic imidazole may well be considerably different in structure, since the removal of the positive charge should have important repercussions on the electron distribution in the ring). We may adopt a simplified model suggested by Donohue, et al., as being compatible with their data within the limits of experimental error. It is illustrated in the two imidazole groups around the Cu atom in Fig. 5. All the internal bond angles are taken as being very close to 10So,and all C and N atoms shown are cy planar within very narrow limits (within 0.017 in the case of histidine hydrochloride monohydrate). An attached carbon in the 4-position, as in histidine and 4-methylimidazole, is also coplanar with the atoms of the ring. AUowing for the usual C-H bond distances and van der \I-aals radii for the hydrogen atoms, i t proves to be impossible to place four imidazole rings, even without substituent (21) See. for instance, A F. Wells, "Structural Inorganic Chemist r y , " 2nd E d . , Oxford, 1950; also J. C. Bailar, Jr. (editor) "The Chemistry of t h e Coordination Compounds." Reinhold Publ. Corp., S e w York, iV.Y., 1956. (22) See, for instance, t h e discussion b y J . Bjerrum, C. J . 1Jxllhausen and C. I. J#rgensen, Acta Chem. Scand., 8 , 1275 (1951). (23) J. Donohue, L. R. I a v i n e and J. S Rollett, A r i a C v s s t . , 9, (is5 (1956)
AMINECHEMISTRY OF
May 5 , 1957
methyl groups, around the central Cu(I1) ion, if it is assumed that all the rings are coplanar, and lie in the plane defined by the C-N bonds. The nature of the steric hindrance involved is shown '5 Fig. 5 , in which the C-H distance is taken as 1.09 A., and the van der Waals radius of the hydrogen atoms as 1.10 A . The marked overlapping shown between the van der Waals radii of the adjacent imidazole rings in Fig. 5 obviously cannot be obviated by any reasonable change in the assumed dimensions. Presumably some or all of the imidazole rings must be rotated out of the plane of the figure, around the Cu-N bonds, so as to make mutual accommodation easier. Probably there is also some distortion of the orientation of the Cu-N bonds, so that they do not all lie in a single plane.24 The insertion of a methyl group in the 4-position on the ring gives rise to new stereochemical problems and also to new possibilities of isomerism, as illustrated in Fig. 6. To minimize steric hindrance i t seems probable that the binding will occur chiefly with the 1-nitrogen, as for the imidazole ring shown on the right hand side of Fig. 6. This places the methyl group as far away as possible from the central copper ion. I n the binding of 2,4-dimethylimidazole, however, it is inevitable that one of the methyl groups must be on a nitrogen atom immediately adjacent to the copper ion. Neverthe(24) Bjerrum, e l ai.,** conclude t h a t t h e C u ( N H s ) r + + complex, and other analogous complexes, are distorted octahedral structures, with a t t a c h e d water molecules above a n d below t h e plane defined b y t h e 4 Cu-N bonds. If this is t r u e for t h e imidazole complexes, t h e stereochemical problem is n o t very much changed from t h a t outlined in t h e text here. T h e t w o a t t a c h e d water molecules, however, m a y make t h e a t t a c h m e n t of 4 imidazole molecules involve a n even tighter fit t h a n we have suggested.
[CONTRIBUTION FROM
THE
THE
PENTABORANE B5H9
2129
v
NkN-C;;INJ, 7 I r N
Fig. 6.-Combination of 4-methylimidazole with Cu(II), showing the two possible isomeric arrangements; the one shown on the right is presumably preferred. The other two coordination positions are shown as being occupied by water molecules.
less the rather incomplete studies reported here on 2,4-dimethylimidazole indicate only a slight decrease in its tendency to coordinate with copper as compared with imidazole or 4-methylimidazole. These findings reinforce the conclusion that the Cu-N bonds cannot be coplanar in the tri- and tetra-coordinated complexes. X-ray diffraction and spectroscopic studies on these complexes may serve to clarify these problems, to which we can give no definite answer here.25 Acknowledgment.-We are indebted to Mr. Charles Lipson for much work on the preparation and purification of the imidazole derivatives studied in this paper, and for some of the preliminary measurements upon them. (25) Compare t h e structure of t h e CuClr- ion i n cesium chlorocuprate, reported b y L. F. Helmholz a n d R. F. K r u h , THISJOURNAL, 74, 1176 (1952).
CAMBRIDGE A N D BOSTON. MASS.
DEPARTMENT O F CHEMISTRY, UNIVERSITY
OF
SOUTHERN CALIFORNIA]
Amine Chemistry of the Pentaborane B,H, BY ANTONB. BURG RECEIVED NOVEMBER 13, 1966 The structure of B5Hg suggests certain modes of reaction which its amine chemistry appears to confirm. I t adds trimethylamine a t -78" t o form B5Hs.2Me3N,which on heating in vacuo is partly dissociated into the original components and partly converted to Me&BH3 and (BH),. On heating with excess Mearc', the adduct yields 2Me3NBH3and BH polymers incorporating Me3N, which lends thermoplastic character. Either Mez" or aminoboron hydrides such as MezNBHz or (MeZN)*BH remove BHI from BjHs on heating, and much of the new (Me2J)3B3H4(m.p. 95"; h.p. est. 220") is formed, of similar volatility, also are obtained. Both compounds, which seem to repreSmall yields of the new liquid (MezN)zB4He, sent a large new class, are presumed to have cross-ring structures wherein all B and 1\; atoms are four-coordinate. The (Me2N)zB3H4is especially unreactive and thermally stable but can be converted by heat to still more inert new materials.
The structure of the pentaborane BsH91$2 is such that the removal of two BH3 groups from the molecule-as by the use of a tertiary amine to form 2R3NBH3-could occur by breaking only bonds of order less than one, and without shifting any hydrogen atoms from one boron atom to another. The remainder of the molecule then would be a B3H3 unit which could not persist as a simple B-B-B chain hydride, but would convert immediately to a high-polymer form. These ideas correlate with some experimental results obtained by the author (1) K. Hedberg, M. E. Jones a n d V. Schomaker, THISJOURNAL, 73, 3538 (1951). (2) W. J. Dulmage a n d W. N. Lipscomb. i b i d . , 7.3, 3639 (1951).
in the year 1937, during a period of collaboration with Professor H. I. Schlesinger a t the University of Chicago. It was found that the adduct BsH9. 2(CH3)3N would form slowly a t -79' and upon warming in vacuo it would decompose in two ways : dissociation into the original components and the formation of (CH3)3NBH3 and a yellow residue. The two ways of decomposition, occurring simultaneously, suggested the possibility that the adduct had two forms with different types and strengths of bonding. On heating with more trimethylamine, the yellow solid became almost colorless, with slight production of (CH3)3NBH3,and approached the composition (BH),, containing only a very
