Indian .Iotlmal of Chemistry VoL 38A, Febmary 1999, pp. 161 -1 65

Synthesis and characterization of palladium(II) complexes of purines and amino acids

R I1avarasi , M N S Rao & M R Udupa*

Department of Chemistry, Indian Institute of Technology, Madras 600 036 , India

Received 5 May 1997; revised 17 November 1998

Complexes of types [Pd(CH3COO)(na)])x H20, Hna=adenine (Hade) or guanosine (Hgllo) , x=2· or 3; [Pd(CH)COO)2 (O.S Hado)b HcO, Hado=adenos ine; [Pd(NH j)(na)(aa)3H 20 , Hna=Hguo or inosine (Hino), Haa=glyc ine or alanine and [Pd(NH ,J(gly)(O.5 ade)hNO.IH20 have been synthesised and characterized by elemental and thermal analyses, electronic, infrared , IH NMR spectral and XPS studies. In acetato complexes, adeninate and guanosinate ac t as bridging ligand through the ring nitrogens N3 or I and 9, and I and N7 respectively givi ng polymeric structure while adenosine bridges the Pd( II ) centers through N I and 7. In amino acidato complexes, nucleosides coordinate through N I to Pd~I1) and adeninate bridges the two adjacent Pd(I1 ) through N I or 3 and 9.

It has been well-establi shed that ceJ1ain platinum and palladium l.J complexes are of biologica l import ance due to their carcinostatic activity and interestin g biological chemistry. Charl son el al. 4 havc reported that cesium cis-dichloroserinatopalladate( ll) indLlees filamental growth in E coli. The cOll1plexes of palladium(lI ) wi th ami no ac ids such as glyci ne , serine and glutami ne have al so been reported5

.u to be acti ve

against certain tumours. Also , it is well known? that the carcinostatic action of the drugs is due to their interaction wi th nuclear DNA. The present note reports the synthesis and characteriza ti on of the complexes o\" Pd(ll) with amino acids and nucl eic acid den vati\'es. Such studies may also be useful 111

understanding protein-nucleic ac id interact ions in many biological processesR

•

Materials and Methods Palladium chloride , palladium acetalL' , nue1c: ic

acids and amino ac ids used were cOlll lllerci:ll ly ava ilable samples. The complex cis-Pd(NII d"C12 \\'as prcparcd by following the litera ture I11 cI 11 0C( The elemental anal yses were carried out using Il er:1L'us CHN-O-R APID analyser. Thcrllloanal yti c tl stl!dics were made on a Stanton silllultaneo Li s thcrI ~l al

analyses instrument (model 7 ~ I) in stati c air :11 a heating rate of IODC/min. The infrared and cb:trollic spectra were recorded on Shimadzu IR-470 and l V-3100 spectrophotometers respecti vely . TIll' III Nl\ IR data were obtained on a JEOL J M-J SX 400 111 z spectrometer at rool11 temperaturc in DM SO-d(, \\ 'ith TMS as the external tTlcrenee. The X-ray

photoelectron spectra were recorded on an ESCA LAB MkIl spectrometer using MgKa radiation (1253.6 eV) and carbon (CI S 285.0 eV) as an internal standard .

SyntheSis o/aceralo complexes To a palladium(lI) acetate (1 .0 mmol in 20 ml of

ace tone) solution was added the corresponding nucleic acid constituent (1 .0 mmol in 25 ml of H20) solution slowly through the walls of the beaker in hot condition and st irred for 3 h. The resultant yellow precipitate obtained was collected by centrifugation, washed with hot water followed by acetone and air dried ; yield around 95%.

Synthesis a/all/ ina acidato complexes cis-Pd(N H)):CI2 (1.0 mmol) was added to a

solution of AgNOJ (2 .0 mmol in 15 ml of H20 ) in a beaker covered wi th black paper and the contents were stirred for 2 h. The AgCI precipitate obtained was removed by filtration and to the clear yellow solution amino ac id (1.0 mmol in 5 ml of H20) soluti on was added slowly with continuous stirring followed by the nucleic acid constituent (1.0 mmol in 25 1111 of H20) solution , and the contents were refluxed for I h. A crystalline yellow .precipitate fOn1led was colkcted by centrifugation, washed with hot water followed by acetone and air dried; yie ld around 80°;( ..

Results and Discllssion Aeetalo compicxes wcre isolated uSing

palladium( II ) ace tate in whic h ace tate beh:1Ves bot h as

162 INDIAN J DiEM, SEC. A, FEBRUARY 1999

T<Jb1c I-AJ1 ~d )'ti cal data of the complexes

Complexes Found (Caled), % C H N Pd

I [Pd(CH ,COO)(alic)j2H,0 2-U)2 3.02 2U6 3 1.60 (250:' ) (3 .30) (20.87) (31.7 1)

2 [Pd(C H,COO), (05 Hado»)2H10 '27.25 4.00 8.30 26.3 1 (2(,.22) (4.52) (8 .50) (25 .82)

3 [Pd( CH ,COO)(guo)j:\ H20 18.2 1 3.98 13.88 20.36 (2 87.1) (4.21 ) ( 13 .96) (21.2 1 )

4 [Pd( NH, )(gl y)(guo)j.lH,O 28.3 7 4.22 18.86 19.7 1 (2 S .')~ ) (4.33) ( 18.34) ( 19.90)

5 [Pd( NH.l(01 I<J)(guo)jJH 20 28AI 4.22 18.56 19.27 ( 18.9~) (4 .33) ( 18.34) ( 19.32)

6 [Pd( NH, )( gly )(lno)j.lII ,O n30 3.99 16.91 2U6 (nn) (4.M) ( 16.20) (20.52)

7 [Pd( NH ,)(aI01)( In o)].III ,O 2S.5S 4.35 15.91 18.78 (2'.13 I) (4 .92) ( 15.78) ( 17.97)

8 [Pd(NH,)(g ly)(O) ;Jlic») ,NOjH,O I S. ')2 2.80 23.95 35.92 (I S. 2') I (3 .07) (23 .71 ) (36.0 I)

Hade!=adenl nc. HOJd o=alicnosi ne, Hguo=guanosine. II ino=illosill e, Hgly=glyc ine, Ha la=alanine

Table 2-Principal infrared spectral data (cm I)

Complexes v sym V"sym COO, ONH2 oH 2O VC=N, VC=C ring Vrd.N VPd-NO COO Vco Purines stretching

(purines) I [Pd(CH ,COO)(ade»)2H,0 1400sh 15655 16515h 16205 16035h, 15885, 545m 405w

1395m, 1300m 480w 2 [Pd (CH,COOHO.5 H01do »),2H,O 14895 16355 16585 16 18br 15 805h, 1568w 546:11 410w

14055h 1560m 1540m 482m 3 [Pd(CH,COO)(guo)j3H,O 14 125h 15625 16655 16305 1565s, 1500m 549m 406w

1473m, 1350m 49 1w 4 [Pdt H')(g ly)(guo»)3H 20 16435h 166 15 1620br 1563m, 1503 m, 551m 4 15w

17005 14855,1355m 423 w 7 [Pdf H ,)(OJ IOJ)( In o)j:\H,O 165 15h 1632br 15635, 1503m 553w 420w

17005 1485s, 1350m 430w 8 [Pd(N H d(g ly)(O.5 ade)j ,NO,H,O 1640m 16595 1625br 16035h, 1588m, 5 12m 411w

1397w, 1300w 473w

s---strt:JI1g , sh-shoulder , br--broad, m--medi um, w-weak, vw-vcry weak .

a base and as a ligand . The interaction or'these complexes wllh various amino acids under different conditions ga\T no mixed nucleic ac id-amino acid complexes. Ilowe ver, the reaction of the cis ­diamminedichloropalladium(l l) with amino acid and nucleic acid . resulted in the iso lation of mi xed nucleic acid-amino acidato complexes. The acel :l lo complexes containing nucleosides and acc:t:lto­adenosine complex wcre soluble in DMSO. The molar conductance of the complexes (10-3 AI) in DMSO was round to be 4-6 ohm-Icm" ind icating the non-electrol ytic nature of the complexes. The complexes were round to be diamagnetic :lS expl'Ckd from the +2 oxidation stak of ;Pc metal. The analytical data or the complexes are given Il1 Table I .

Thermogravimetri c and differential therm::ll anal yses were carried out in air, in order to understand the thermal behaviour of the complexes. The acetato complexes showed two-step mass loss in air. The fir st step mass loss was due to dehydration as evident ('rom the mass loss \\'hich occurred in the temperature ra nge 50- 120°(' \\ith a bro<ld endothermic peak around 90°(' in the DTA curves. The second step due to oxidative decomposition of the ligands b~'gins in the range 20U-2200e and ends in the range 400-5()()OC with two exothermic peaks around 400 and 470°(, in the DTA curves. The amino acidalo compiL'\L'S showed three step mass loss processes. T ile first s\L'p was due to dehydration which occurred in the ran ge 65- 115°(' and was supported by the appearance of

, ".

...

ILA V ARASI et al. : STIJDIES OF Pd (II) COMPLEXES 163

Fig. I-XP~ spectra for (a) guanosine of Nls region and (b) [Pd(CH3COO)(guo )]3-H20 of N I s region. Spectra are deconvoluted to show different components.

endothermic peak around 90°C in the DT A curves. The multiple DT A peaks were due to deaminat ion with an endotherm around 245°C and successive decomposition of ligands in the range 250-420°C wi th three exothermic peaks around 410, 450 and 470°C. No attempts were made to characterize the intermediate products of decomposition. The glycinato-adenine complex started losing ligands at 200°C and the decomposition was completed at 500°C. The final residue was found to be PdO in :11 1 the complexes. The onset of decomposi ti on temperature suggests that the monomeric complexL's are thermally more stable as compared to the dimL'ric complex .

Electronic al/d I R spectral studies

The electronic spectra exhibit absorption band around 410 nm due to d -Nl transition of Pd(II) which is characteristic of square planar geometry. An intense peak around 300 nm indicates purine to Pd charge transfer in the complexes 10. The principal infrared frequencies and their assignments are presented in Table 2. Strong multiple bands around 3410 cm- I

have been assigned to VOH of water and V NH of ligands in the complex. It was very difficult to assign all the

Binding energy(eVl

Fig. 2-XPS spectra for (a) : adenine of Nis region and (b) [Pd(NH3)(gly)(O.S ade)hN03H20 ofNls region.

vibrational frequencies but attempts have been made to specify characteristic frequencies which will support the coordination of ligands in the complexes. The complexes (1) and (8) show strong bands around 3328 and 31G8 cm- I due to V NH2 of adenine. The ONH2

of adenine is located around 1665 cm -I indicating that it IS neither deprotonated nor involved in coordinati0l1. A strong absorption band of the pyrimidine moiety of adenine at 1600 cm- I undergoes large splitting and appears at 1603 and 1558 cm- I

suggesting the coordination of pyrimidine nitrogen. The vibrational frequencies at 1415, 1330 and 1305 cm- I in free adenine are due to the imidazole fragment and which appear at 1395 and 1300 cm- I in complexes. This indicates the deprotonation and coordination of N9 to metal I I . Therefore adenine may be coordinated through imidazole nitrogen, N9 and pyrimidine nitrogen N3 or Nl . The Vasy and vsym COO of the acetate group appear at 1565 and 1400 cm- I

(,0.v= 165 cm- I) suggesting the bridging mode of

164 INDIAN J CHEM, SEC. A, FEBRUARY 1999

acetate bindingl2. In complex (2), two sets of carboxylate stretching frequencies could be located, namely Vasy COO (1635 em-I) and Vsym COO (1405 em-I) with ~v=230 cm-1 suggesting monodentate acetate andvsym COO (1560 em-I) and Vsym COO (1489 em-I) with ~v=7l cm-1 corresponding to bidentate chelating acetate. The absorptions around 1600, 1580 and 1535 cm- I and 1495 and 1350 cm- I in guanosine arid inosine have been assigned to the combination of Vc=c, VC=N and stretching vibrations of the pyrimidine and imidazole ring respectively. These frequencies were shifted to lower wave numbers by about 25 cm- I in the complex (3) suggesting deprotonation and coordination l3.14 of guanosine to the metal. The difference in the symmetric and asymmetric stretching frequencies of carboxylate with ~v=150 cm- I was observed in accordance with the bridging acetate group . The bNH2 at 1665 cm -I of

guanosine and vco at 1700 cm- I of guanosine and inosine do not undergo any significant shift in the corresponding complexes, suggesting its non­in volvement In coordination. The vibrational frequencies compared with those of free ligand of the amino acidato complexes (4 and 7) at 1563, 1503 , 1485. and 1350 cm - I indicate the nitrogen coordination of the pyrimidine ring. The absorption at 1643 cm- I is characteri stic of bidentate amino acidato group due to asymmetric carboxylate stretching 's. The complex (8) shows a strong band at 1390 cm- I

characteristic of VNO nitrate ion ' 6. The stretching

frequencies due to Pd-N and Pd-O were observed at 545 , 480 cm- I and 405 cm- I respectiveJi 7

•' 8 in the complexes.

I H NMR studies The 1 H NMR spectrum recorded in OMSO-d6

exhibits two singlets at b 7.94 and 7.74 ppm due to H8 and H2 protons respectively' 9. In the spectrum of complex (2), both H2 and H8 of adenosine shift downfield by 0 .2 ppm suggesting simultaneous participation of Nl and N7 in coordination to palladium . This complex, in addition, showed two signals around 8.70 and 8.40 ppm which disappeared on 0 20 exch'Vlge. These were assigned to NH2 of adenosine a1 the NH2 protons of free adenosine appeared at 6.98 ppm. The observed split and large downfield shift of the NH2 signal may be explained by a possible intramolecular hydrogen bonding interaction20. The amino hydrogen of adenosine and one of the oxygens of the acetate group may be

involved in hydrogen bonding and may restrict free rotation of the NH2 group about the C-N bond suggesting the presence of two non-equivalent hydrogens. In confim1ation, with the IR data, it may be inferred that the complex (2) is dimeric with the bridging of adenosine through N I and N7 in addition to two types of acetate groups namely, terminal monodentate and bidentate chelating acetate.

The proton signals of inosine observed at 7.7 and 7.5 ppm were due to H8 and H2 respectively. The resonance due to H2 is shifted downfield by 0.4 ppm and that due to H8 is unaffected in the spectra of (6) and (7) suggesting N I of the inosine is the binding site for the meta l .ion . The complexes (4) and (5) exhibit signal at 7.ft3 ppm due to H8 without any shift from that of free ligand . This shows that N7 is not involved in binding . The complexes containing alanine show quartet at 3.43 ppm due to CH resonance while in the glycine complex, the CH2 resonance ·appears as a singlet at 3.94 ppm. A broad signal around 4.3 ppm in all the amino acidato complexes indicates the resonance due to ammonia which is bonded to the metafl .

ESCA analysis Figures I a, I b, 2a and 2b show the XPS spectra of

guanosine, complexes (3) and (8) respectively. Using a spectral deconvolution program22

, we evaluated the binding energies corresponding to nitrogen atoms. The peaks obtained from the deconvolution of the nitrogen Is core level indicate the presence of three different nitrogen atoms. The peaks with intensity ratio of about 2:3 at 397.2 and 398.6 eV are due to pyrimidine Nl and N3 and the combinations of N7, N9 and NH2 of guanosine nitrogens respectively. The binding en€:rgy varied inversely with the electron density23 . The FWHM value increases by 0.5 units upon complexation. The complex (3) exhibits peaks at 397.2.eV which is attributed to Nl and N3 nitrogens, at 398.8 eV due to N9 and NH2 nitrogens with area reduction compared to that of ligand and at 400.1 eV with an intensity ratio of 2:2: 1 in the deconvoluted nitrogen-Is spectrum. The new peak with a shift to a higher value of 1.5 eV of N7 indicates its coordination to Pd(II) . These results further support the IR data suggesting bonding of N 1 and N7 to Pd(II). No shift in the binding energy of N 1 was noticed because its coordination occurred by deprotonation.

The complex (8) showed four peaks at 396.9, 397.3, 397.7 and 398.2 eV in the intensity ratio

t

"

ll.,A V ARASI et al.: SnJDIES OF Pd (II) COMPLEXES 165

1 :2:2 :3. The spectrum of free adenine showed three peaks with intensity ratio 2:2: 1 at 396.9 (Nl, N3), 397.2 (N9, NH2) and 398.2 (N7) . The same argument as above holds good and an additional peak at 397.7 eV and the intensity ratio obtained suggest the coordination and the numb~r of nitrogen atoms in the complex. The peaks at 396.9 and 397.3 are assigned to N3 and N9, NH2 nitrogens respectively. The peaks at higher values 397.7 and 398.2 eV are attributed to coordinated nitrogens N 1, NH) and N7, NH2 of glycine and N of nitrate ion in the complex respectively.

The difference in coordinating behaviour of purine ligands with Pd(II) metal have been evaluated. The acetato-nucleic acid complexes are dimeric or polymeric, bridged by purine ligands and the amino acidato-nucleic acid complexes are either monomeric or dimeric. Unlike Hguo and Hino, Hado did not give the expected mixed amino acidato-nucelic acid complex probably due to the absence of Nl hydrogen and presence of sugar moiety at N9. The glycinato­adenine complex is dimeric with the bridging of adenine.

References I Rosenberg B, Vancamp L, Trosko J E & Mansour V H,

Nature (Lolldon), 222 (1969) 385 . 2 Kirschner S, Maurer A & Dragulesku D, J Clin Hematol

On col, 7 ( 1977) 293. 3 Kifschner S, Maurer A & Dragulesku D, J Clin Hematol

• Oncol. 7 ( 1977) 190. 4 Charlson A J, McArdle N T & Watton E C, lnorg chim Acta,

56 (1981) U5 .

5 C;:harl son A J, Benner R J, Gale R P, McArdle N T, Trainor K E & Watton E C, J Clill Hematol Oncol, 7 ( 1977) 294.

6 Trainer K E & Watton E C, Cancer Treat Rep, 61 ( 1977) 469 .

7 Rosenberg B. Biochemie. 60 ( 1978) 859. 8 Sabat M. Satyshur K A & Sundaralingam M, J Am chern Soc,

105 ( 1983) 976 . 9 Layton R, Sink D W & Durig J R, J lnorg nuc/ chern , 28

( 1966) 1965 . 10 Basall ote M G, Vilaplana R & Gonazalez-Vilchez F, Trans

Met Chem. I I ( 1986) 232 . II Mikul ski C M, Cocco S, Defranco N, Moore T & Karayann is

N M, llIorgchim Acta , 106( 1985)8 . 12 Nakamoto K, Illf rared alld Raman spectra u( inorganic and

coordillolioll compol/nds (Wiley, New York), 1978.

13 Theodorou V, Nicolaou A & Hadjiliadis N, lnorg chim Acta, 208 (1993) 91.

14 Frommer G. Scholl horn H. Thewalt U & Lippert B, Inorg Chern, 29 (1990) 141 7.

15 Petit L D & Bfzer M, Coord chem Rev, 67 ( 1985) 97.

16 Karayanni s N M, Mikulski C M, Pytlewski L L & Labes M M, J inorg nuci Chern , 34 ( 1972) 3139.

17 Watt G W & Klett D S, Inorg Chern , 5 ( 1966) 1278.

18 Fujita J, Martell A E & Nakamoto K, J chern Phys, 36 (1962) 324.

19 Beaumont K P, Mcauliffe C A & Friedman M E, In org chim Acta, 25 (1977) 241 .

20 Krizanovic 0 , Sabat M, Beyerle-Pfnur R & Lippert B, JAm chern Soc, 115 ( 1993) 553 8.

21 Schwarz F, Lippert B, Scholl hom H, Thewat U, Inorg chim Acta, 176 ( 1990) 113 .

22 Chandramouli G V R, Lalitha S & Manoharan P T, . Computers Chem, 14 ( 1990) 257 .

23 Politzer P & Daiker K C, The force concept in chemistry (Van Nostrand, Reinhold , New York), 1981.