Inorg. Chem. 1994, 33, 217-226
217
Amino Acid Complexes of Palladium(I1). 1, NMR Study of the Reactions of the Diaqua(ethylenediamine)palladium(II) Cation with Ammonia, Betaine, and the Amino Acids +NHs(CH2),,C02- (n = 1-3)’ Trevor G. Appleton,’ Alicia J. Bailey, Danny R. Bedgood, Jr., and John R. Hall Department of Chemistry, The University of Queensland, Brisbane, Qld., Australia 4072 Received June I I, 1993”
1sN NMR spectra were obtained for solutions of [Pd(en-lSN2)(H20)2I2+(1) and the complexes formed from it on addition of alkali, [(Pd(en-15N2)(p-OH)),]n+ (n = 2, 3), and [Pd(en-lSN2)(0H)2]. In the presence of weak donor anions, NO3-, S042-, and C104- and dioxane, the 15N NMR peak from 1 was broadened at 298 K, owing to exchange between H20 and these ligands. When betaine ( + ( C H S ) ~ N C H ~ C Obet) ~ - , reacted with 1, the major lSN NMR peaks at 277 K were assigned to [Pd(en)(bet-0)(H20)l2+ and [Pd(en)(bet-O)#+. At higher temperatures, the peaks broadened and coalesced, until by 353 K there was a broad singlet, indicating that intermolecular exchange of betaine between the free ligand and these complexes was rapid. The products of reactions of 1 with ammonia depended on pH. [Pd( en) (NH3) (H20)]2+, [Pd(en) (NH3)21 2+, [Pd(en) (NH3) (OH)]+,and [(Pd(en) (NH3))2(pOH)]3+ were characterized in solution by ISN NMR. Reaction of 1 (in excess) with glycine (Hgly) gave [Pd(en)(gly-N,O)]+ as the dominant complex over the pH range 4-10. Above pH 10, [Pd(en)(gly-N)(OH)] formed. With excess glycine, at high pH, [Pd(en)(gly-N)z] was the dominant complex. Near pH 2, [Pd(en)(Hgly-0)(H20)l2+ was in equilibrium with the N,O-chelate complex, free glycine, and 1. cis- [Pd(NH3)2(H20)2]2+ with glycine, without addition of acid or base to adjust pH, gave initially [Pd(NH3)2(gly-N,0)]+, but with standing, reaction with the acid liberated gave the isomer of [Pd(NH3)(H2O)(gly-N,0)]+ with ammine trans to glycinate 0, as well as [Pd(H20)2(gly-N,0)]+. Reactions of &alanine (+NH3(CH2)2C02-, Hoala) with 1were generally similar to those of glycine, except that the N,O-chelate complex was less stable relative to [Pd(en)(Hi3ala-0)(H20)]2+at low pH. Reaction of 1 with y-aminobutyric acid ( + N H ~ ( C H Z ) ~ C OHyaba) ~ - , gave a mixture over the pH range 4-8 of the chelate complex [Pd(en)(yaba-N,O)]+ with the isomers of [(Pd(en)(p-yaba)]#+.
Introduction In introducing their review on palladium(I1) complexes with amino acids and peptides,2 Pettit and Bezer commented that interest in platinum(I1) amino acid complexes had been stimulated by the discovery of anticancer properties of platinum(I1) compounds. They remarked that the kinetic inertness of platinum(11) complexes makes them difficult to study, so that “due to the similarities in the general chemistry of Pt(I1) and Pd(II), as well as the increased rates of reaction of Pd(I1) ions (on average approximately 103 times faster than platinum), palladium analogues are studied instead of, or as well as, the platinum compounds”. Even in 1985, their view of the prospects of elucidating platinum(I1) amino acid chemistry was probably unduly pessimistic, and since then, there has been considerable progress in the chemistry of platinum(I1) complexes with amino acids and peptide^.^-^ Much of our own work has focused on reactions of cis-[Pt(NH3)2(H20)2I2+with these ligands.G8 Our results, and those of others,s have shown that amino acids frequently react with platinum(I1) to give an initial product which is “metastable”, a kinetically-preferred product which must Author to whom correspondence should be addressed. Abstract published in Advance ACS Abstracts, December 1, 1993. (1) Presented in part at the Ninth National Conference of the Royal Australian Chemical Institute, Melbourne, Vic., Australia, Dec 6-1 1, 1992; sec Inorganic Chemistry Division Abstract TI-60. (2) Pettit, L. D.; Bezer, M. Coord. Chem. Rev. 1985, 61, 97. (3) Kozlowski, H.; Pettit, L. D. In Chemistryof the Platinum Group Metals. Recent Developments; Hartley, F. R., Ed.; Elsevier: Amsterdam, 1991; p 530. (4) Schwederski, B. E.; Lee, H. D.; Margerum, D. W. Inorg. Chem. 1990, 29, 3569. (5) Altman, J.; Wilchek, M. Inorg. Chim. Acta 1985, 101, 171. (6) Appleton, T. G.; Hall, J. R.; Ralph, S.F. Inorg. Chem. 1985,24, 673. (7) Appleton, T. G.; Hall, J. R.; Ralph, S.F. Aust. J. Chem. 1986,39,1347. (8) Appleton, T. G.; Hall, J. R.; Hambley, T. W.; Prenzler, P. D. Inorg. Chem. 1990, 29, 3562.
0020-16691941 1333-0217$04.50/0
overcome a significant energy barrier to rearrange to the thermodynamically- preferred compound. Specific examples are mentioned below in the context of comparisons between the reactions of the two metal ions with particular ligands. Our aim on embarking on the present study was to carry out reactions with a palladium species which would, as much as possible, be analogous to those we had studied with cis-[Pt(NH3)2(H~0)2]~+. We expected that with the more labile palladium species we would obtain the thermodynamically-preferred species. As well as being of some interest in themselves, these results would then throw some light on the kinetic and thermodynamic factors which work together to give specific compounds as products from the reactions of platinum compounds. A major tool in our investigations of the reactions of cis-[Pt(NH3)2(H20)2I2+ has been multinuclear NMR spectroscopy. As well as IH and 13CNMR from nuclei present in the amino acid ligands, we have used l5N NMR with the ammine ligands highly enriched in ISN ( I = ‘12). In IsN NMR spectra, a separate peak (with “satellites” from coupling to I95Pt,Z = l/2,34% abundance) is observed for each distinct ammine ligand, and 6~ and 1 4 1 9 5 Pt-lSN) can both provide information about the nature of the ligand trans to that ammine? The only naturally-occurring isotope of palladium with nuclear spin is IOsPd, I = 5/2,22,2%abundance. With its large quadrupole moment, this nucleus is expected to relax rapidly in square planar Pd(I1) complexes.10 There is therefore no information available from coupling constants to themetal nucleus. In a 1SN NMR study of palladium(I1) ammine complexes,lI we showed that SN does depend primarily on the nature of the ligand trans to ammine. We were able to confirm (9) Appleton, T. G.; Hall, J. R.; Ralph, S.F. Inorg. Chem. 1985, 24,4685. (10) Brevard, C.; Granger, P. Handbook of High Resolution Multinuclear N M R Wiley: New York, 1981; p 160. (11) Appleton, T. G.; Hall, J. R.; Ralph, S.F.; Thompson, C . S. M. Aust. J. Chem. 1988,41, 1425.
0 1994 American Chemical Society
218 Inorganic Chemistry, Vol. 33, No. 2, 1994
Appleton et al.
earlier suggestions from UV spectroscopy12J3 that the preferred isomer of [Pd(NH3)2(H20)2]2+ in aqueous solution is the cis isomer. However, our results alsoshowed that theammine ligands bound to palladium are very labile, so that, for example, the isomerization of tran~-[Pd(NH~)~(H~0)~]~+ to the cis isomer proceeds by reactions in which ammine ligands dissociate, rather than by intramolecular rearrangement. It was therefore clear that it would be difficult to make useful comparisons between the reactions of cis- [Pt(NH3)z(H20)2]2+ and its palladium analogue, because the products in the latter reactions would arise largely from ammine redistribution reactions. We therefore used [Pd( e n ) ( H 2 O ) ~ ] ( N 0 ~(1) ) ~ (en = 1,2-diaminoethane) as our palladium(I1) starting complex, with the expectation that thechelate effect would sufficiently hinder redistribution reactions of this ligand to allow a useful exploration of the reactions of 1 with amino acids and derivatives to be carried out. Recent papers1&I6 described reactions of 1 with various ligands, in which the Pd(en)2+ moiety retained its integrity. In this paper we describe the reactions of 1 with the amino acids +NH3(CH&C02- with n = 1 (glycine, Hgly), n = 2 (Balanine, Hoala), and n = 3 (y-aminobutyric acid, Hyaba). We also include the results of one study of the reactions of cis-[Pd(NH&(H20)2]2+ (2), with glycine, to show similarities and differences from the reactions of 1. To assist us in our interpretation of NMR results obtained with the amino acids, we have also studied the reactions of 1 with betaine (+(CH3)3NCH2CO2-,bet) as a model for the carboxylate end of an amino acid and with ammonia as a model for the amine end.
IH spectra were obtained in 2Hz0 and are referenced relative to the methyl signal of 3-(trimethylsi1yl)propanesulfonate (TSS) ( 6 =~ 0). The 21.4-MHz 19sPtNMR spectra were obtained with a JEOL FX-100 instrument, as previously de~cribed.6~ All shifts are positive to lower nuclear shielding (higher frequency). Spectra of nuclei other than IH were IH-decoupled. Preparation of NMR Samples. For all experiments, approximately 0.08 g of [Pd(ONO2)2(en)](with either I4Nor ISNpresent) was dissolved in 0.75 mL of water (IH20 or D20 as appropriate) and approximately 0.8 mol equiv of the amino acid was added. The mixture was warmed briefly, to dissolve all solids, and NMR spectra were obtained from solutions in which the pH was adjusted by addition of 1 M HNO3 or KOH solutions (in IH2O) or D2S04 or NaOD solutions in D20. Reversibility of changes in spectra as pH was changed was frequently checked. An additional 0.8 mol equiv of the ligand was then added, and spectra were again run at various pH values. The pH was measured on a JENCO 6072 pH meter with a Sensorex combination electrode. Preparation of [Pd(gly-N,O)z]. The preparation of crystals of the isomers of [Pd(gly-N,0)2]from K2[PdC14] and glycine in aqueoussolution was described by Coe and Lyons.22 They added no base to remove protons generated by chelation of glycine, so that the yield when their procedure was followed was low. The following adaptation of their method was used. K2[PdC14] (0.1994 g, 0.61 mmol) and glycine (0.1017 g, 1.36 mmol) were dissolved in 5 mL of water. The pH of the solution was adjusted to 4-5 by the addition of 6 M NaOH solution. The pale yellow solid which precipitated was filtered off, washed with a small volume of cold water, and air-dried. Yield: 0.0662 g (42%). Satisfactory microanalyses were obtained. Similar procedures were used for glycine containing either I4N or I5N.
Experimental Section
Results
Starting Materials. Ethylenediamine highly enrichedin ISN(en-ISN2) is commercially available, but is expensive, and so was prepared from ISN-labeledpotassiumphthalimide. Details aregiven in the supplementary material. Ammonium sulfate,glycine, and potassium phthalimide highly enriched (99%) in I5N and glycine 99% enriched in I3C at the carboxyl group, produced by Cambridge Isotopes Ltd., weresupplied by Novachem (Melbourne, Australia). Amino acids, Hgly, HBala, and Hyaba, were used as supplied by Sigma,and betaine monohydrate was used as supplied by Aldrich. Solutions containing [Pd(en)(H20)2]A2(A-= c104-, NO,-, CFsS03-, BF4-) were obtained by the method used by Hohmann and van EldikI4to prepare solutions of the perchloratesalt, by reaction of [PdClz(en)] with an aqueous solution of the appropriate silver salt. An aqueous solution of [Pd(en)(H2O)z](NO3)2was taken to dryness in a stream of air to give [Pd(ON02)2(en)] as a pale yellow solid. Satisfactory microanalyses were obtained. The IR spectrum showed strong bands at 1495, 1471, 1300, and 1274 cm-I (cf. bands assigned to nitrate in cis[Pt(ON02)2(NH&] at 1510 (sh), 1485, 1275 (sh), and 1260 cm-I ). A solution containingpredominantly cis-[Pd(NH3)2(H20)2](NO& was prepared as previously described." NMR Spectra. The 20.2-MHz I5N,200-MHz IH, and 50.2-MHz I3C NMR spectra were obtained with the use of a Bruker AC-200F spectrometer equipped with a 5-mmquadprobe (1H/13C/1SN/'9F). Some IH (400-MHz) and 13C(100.4-MHz) spectra were run on a JEOL GX400 instrument with a 5-mm dual IH/l3C probe. lSN spectra were obtained in IH20 without instrument lock. Some were obtained with the use of a DEPT pulse sequence.18J9 Other lsN spectra were run with broad band IH decoupling. In the latter case, negative nuclear Overhauser enhancement gives rise to negative (emission) peaks, but phase was adjusted so that all spectra were presented in conventional absorption mode. Peaks are referenced relative to the 15NH4+signal (BN = 0) from 5 M I5NH4N03in 2 M HN03in a coaxial capillary.20I3Cspectra were obtained in IH20 (for lsN-enrichedsubstances)without instrument lock or in 2H20 (for substancesnot enriched in lsN) with deuterium lock. The (12) Rasmussen, L.; Jorgensen, C. K. Acta Chem. Scand. 1968, 22, 2313. (13) Coe, J. S.; Hussain, M. D.; Malik, A. A. Inorg. Chim. Acta 1968,2,65. (14) Hohmann, H.; van Eldik, R. Inorg. Chim. Acta 1990, 174, 87. (15) Hohmann, H.; Hellquist, B.; van Eldik, R. Inorg. Chem. 1992,31,345. (16) Zhu, L.; Kostic, N. M. Inorg. Chem. 1992, 31, 3994. (17) Lippert, B.; Lock, C. J. L.; Rosenberg, B.; Zvagulis, M. Inorg. Chem. 1977, 16, 1525. (18) Pegg, D. T.; Doddrell, D. M.; Brooks, W. M.; Bendall, M. R. J . MaRn.
R&n. 1981, 44, 32. (19) Berners-Price, S.J.; Kuchel, P. W. J. Inorg. Biochem. 1990, 38, 305. (20) Jones, A. J.; McNab, H.; Hanisch, P. Aust. J . Chem. 1978, 31, 1005.
reference was internal dioxane (6c = 67.7321). A delay of at least 3.5 s was allowed between pulses to allow carboxylatecarbon spins to relax.
Selected N M R data are listed in Table 1.
NMR Spectra of Palladium(I1) Ethylenediamine Complexes. Since [PdClz(en)] is only sparingly soluble in water, the 15N NMR spectrum of the lSN-enriched complex was obtained in N,N'-dimethylformamide (dmf). The spectrum showed a single sharp peak a t -18.7 ppm. The low nuclear shielding compared ~ in dmf") was with that of lSNin cis-[PdC12(lSNH3)2] ( 6 -57.5 expected, in view of the analogous deshielding of the 15N nucleus in a five-membered chelate ring in platinum(I1) complexes.23 A solution containing [Pd(en)z]2+ (3) was obtained by addition of ( H ~ e n ) ( N 0to ~ )a ~solution of [Pd(e11)(H20)2](N03)~,followed by the quantity of KOH solution required to deprotonate the ligand. When the ethylenediamine ligand was l5N enriched, the 15NN M R spectrum showed a single sharp peak ( A Y I I=~ 1 Hz) a t -20.0 ppm. The IH N M R spectrum of a solution of [Pd(en)2I2+ which had been allowed to stand in D20 solution (to replace N H by ND) showed a singlet at 2.75 ppm.24 The corresponding spectrum of [Pd(en-I5N2)2l2+did not show any resolvable ISN-C-IH coupling. The 13C N M R spectrum of the compound containing I4N showed a singlet a t 47.0 ppm. When 15Nwas present, the signal appeared as a doublet (IJ(W-15N) = 3.5 Hz). Dissolution of [Pd(ON02)2(en)] in water would, by analogy with platinum c o m p o ~ n d s , l ~be J ~expected . ~ ~ to give predominantly [Pd(en)(H20)2](N03)2. The IH and 13C N M R spectra of the 14N-containing compound, in D2O a t pD 1.3, each showed the expected sharp singlet (IH, 2.64 ppm; cf. 2.63 ppm reported for the perchlorate salt by Zhu and Kostic,l6 I3C, 48.39 ppm). The I5N N M R spectrum (298 K) of a 0.2 M solution of [Pd(en1sN2)(H20)2](N03)2 in lH2O a t p H 2.2 showed a moderately broad peak ( A v l p = 3.7 Hz)a t -27.4 ppm. The broadness of the (21) Sarneski, J. F.; Suprenant, H. L.; Molen, F. K.; Reilly, C. N. Anal. Chem. 1975, 47, 2116. (22) Coe, J. S.;Lyons, 3. R. J . Chem. SOC.A 1971, 829. (23) Alei, M.; Vergamini, P. J.; Wageman, W. E. J . Am. Chem. SOC.1979, 101, 5415. (24) Appleton, T. G . ; Hall, J. R. Inorg. Chem. 1970, 9, 1807. (25) Boreham, C. J.; Broomhead, J. A.; Fairlie, D. P. Aust. J. Chem. 1981,
34, 659.
(26) Appleton, T. G.; Berry, R. D.; Davis, C. A.; Hall, J. R.; Kimiin, H. A. Inorg. Chem. 1984, 23, 3514.
Amino Acid Complexes of Pd(I1)
Inorganic Chemistry, Vol. 33, No. 2, 1994 219
Table 1. Selected NMR Data for Ethylenediamine-Palladium Complexes0 6Nb
complex
PH
en
4 12.3 9.6 9.6 4 1
-27.4 -27.9 -29.0 -27.0 -20.0 a -16.8 (d) b -28.7 (s) a -18.7 (d) a -16.0 (d) b -27.3 (s) a -20.0 (d) b -27.0 (s) a -26.2 b -29.5 -28.2 a -26.4d b -29.2d a -18.7 (d) b-28.1 (s) a -20.1 (d) b -24.9 (5) a -16.9 (d) a -14.1 b -28.7 a -19.6 b -25.2 -16.4 a -19.2 b -26.5 a -19.2 b -26.0 a -16.0 b -27.6 -16.4 a -19.7 b -25.3
1 7.2 12.5 4 4 2 4 12
trans ligand H20 OHr-OHp-OH-
other I5N
6c (-c02-)
en
NH3 H2O NH3 NH3 p-OHNH3 OHO(bet) H2O O(bet)
WMY)
H2O N(glY-)
O(glY-)
N(glY-)
c -56.7 (d) b -58.2 (d) c -53.8 (d)
c -56.2 (d) 171.53d
c +9.17 (s)
174.P
c -45.8 (d)
187.4
c -38.6 (d)
b -39.6 (d) 177.1 N(glY-) N(j3ala-) 181.8 O(@ala-) 12 N(Bala-) OH10 N(@ala-) 180.8 7.9 183.7 N(yaba-) O(yaba-) 7.9 N(yaba-) O(yaba-) 7.9 N (y aba-) O(yaba-) 7.9 183.3 N(yaba-) 12 183.5 N(yaba-) OHRecorded at 20.2 MHz for 15Nand 50.2 MHz for 13C,in H20. All compounds have ethylenediaminehighly enriched in I5N. Letters in parentheses indicate multiplicity when all other N atoms present are also IsN: d = doublet; s = singlet. "a". 'b", "c" labels correspond to those in structural drawings and schemes and to peak labels in figures. I5N spectrum recorded at 277 K. Peak broad at 298 K. Spectrum obtained from 13C-enrichedcomplex. 10 4
linecontrastedwith thesharpnessofthelinefrom [Pd(en-15N~)~]2+ (3) mentioned above. The N M R spectra of solutions prepared from [Pd(ONO&(en)] usually also showed relatively weak peaks from [Pd(en)2](N03)2, presumably due to a small amount of redistribution of ethylenediamine ligands during the preparation of the solid dinitratocomplex ( [Pd(H20)412+would also be formed but would not be detected by NMR).27 The sharp peak due to [Pd(en-lSNz)2]2+ (3) impurity provided a useful check that line broadening was not due to poor instrument tuning. If excess ( H ~ ~ I I - I ~ N ~ )was (NO added, ~ ) ~ it also showed a sharp singlet at 9.91 ppm. The broadening was therefore not due to a reaction in which ethylenediamine exchanged between palladium ions. The line width was significantly dependent on concentration of the compound, becoming narrower for more dilute solutions. Addition of NaNO3 caused an increase in line width, to 1 1.2 Hz in saturated NaN03 solution. These data are all consistent with the existence of an exchange between water and nitrate ions as ligands which was not fast enough on the N M R time scale to completely average the environments of the 15N nuclei. With cis-diammineplatinum(I1) complexes, separate 15NN M R peaks are observed for the diaqua and aqua nitrato complexes, but the latter are relatively weakunless the nitrate concentration is high.26 To produce the observed effect with the palladium complex, there must be a greater tendency for nitrate, relative to water, to coordinate to palladium than to platinum. Addition of Na2S04 had a similar broadening effect. The 15N N M R peak from a 0.5 (27) We propose that this redistribution occurred during the isolation of solid [Pd(ONO2)2(en)], since the spectrum of [PdClz(en)] in dmf did not show any peaks from [Pd(en)2]2+and solutions of [Pd(en)(H20)2](NO~)2 prepared directly from reaction of [PdCll(en)]with aqueous AgNO3 solution showed only a very weak peak.
M solution of [Pd(en-1SN2)(HzO)~](C104)2 (prepared in situ by reaction of [PdClz(en)] and 2 mol of AgC104) at pH 2.6 was also relativelybroad (Av1/2= 3.5 Hz) and became broaderon addition of NaC104. In contrast to the case of platinum analogues,26.28 there must be significant coordination of perchlorate to palladium. The addition of dioxane, which could also act as an 0-donor ligand, also caused significant broadening. The 15NN M R peaks obtained under comparable conditions from solutions where the counterion was CF3S03-or BF4- were significantly sharper (
