Indian Journal of ChemistryVol. 31A, February 1992, pp. 106-109

Mixed ligand complexes of palladium(II) and platinum(II) withmethionine and purines

Badar Taqui Khan" & K Murali MohanDepartment of Chemistry, University College of Science, Osmania University, Hyderabad 500 007, "India

andG Narsa Goud

Department of Chemistry, Nizam College, Osmania University, Hyderabad 500 001, India

Received 6 March 1991; revised 13 May 1991; accepted 9 July 1991

Mixed ligand complexes of Pt(II) and Pd(II) with methionine (MetH) as primary ligand and purines-adenine, guanine and hypoxanthine-as secondary ligands have been prepared by reactingcis-[Pd(MetH)CI2l (1) and cis- [Pt(MetH)CI2l (2) with adenine, guanine and hypoxanthine in I: I molar ratio.The complexes have been characterized on the basis of analytical, conductivity, and fR, electronic and IHNMR spectral data. In these complexes methionine is bound to the metal ion through amino nitrogen andsulphur atoms. The purines are bound to the metal ion through nitrogen (N7) ofthe five-membered ring andare present in a configuration trans to methionine sulphur. This indicates a higher trans directing ability ofsulphur compared to that of amino nitrogen of methionine. Conductivity data show that the complexes areI :I electrolytes.

The discovery of anticancer activity of certainplatinum coordination compounds I and use ofcis-Pt(NH3hCI2 (cis-platin) as a drug in the treatmentof several human tumours-, have led to an upsurge inresearch on platinum complexes. Efforts have beendirected to synthesize less toxic analogues ofcis-platin and to study their interaction withtumours3-(" and ONA and its constituents? -II. Thepreparation ofless toxic complexes than cis-platin ispossible by the substitution of amine ligands in thesecomplexes by molecules found in biologicalsystems7•11. Many Pt(II)-amino acid mixed ligandcomplexes and ternary complexes ofPd(lI) and Pt(lI)with amino acids and nucleosides!? -15 were also.reported. Earlier we had reported 16 the interaction ofcis-dichloroplatinum(II)-amino acid complexes withsome purines, pyrimidines and nucleosides. In thispaper, we report the interaction of cis-[Pd(MetH)Cl2land cis-[Pt(MetH)CI2l (MetH = methionine) withadenine, guanine and hypoxanthine.

Materials and MethodsChromatographically pure DL-methionine and

purine bases were obtained from Sigma ChemicalCompany (USA). Samples of palladium chloride andpotassium hexachloroplatinate (AR, 98% pure) werepurchased from Johnson Matthey Company (UK)and Alfa Ventron (USA) respectively. Palladiumchloride was converted to potassium

tetrachloropalladate(II) by heating with potassiumchloride solution in 1:2 molar ratio 17. K2[PtCI6l wasconverted to potassium tetrachloroplatinate byreduction with hydrazinium hydrochloride!". Theparent complexes, cis-dichloro(methionine )palla-dium(II), 119, and cis-dichloro-(methionine)plati-num(II), 220, were prepared by publishedprocedures.

The elemental analyses of the complexes werecarried out at the Australian Mineral DevelopmentLaboratories, Australia and CORI, Lucknow, India.The chloride present in the complexes was estimatedat Indian Institute of Chemical Technology (IICT),Hyderabad, India, using a published procedure>'. IRspectra were recorded in KBron IR-I 2Perkin-Elmer577, 337 and Beckman spectrophotometers. Theelectronic spectra of the complexes were recorded on aShimadzu UV 240 instrument at nCT, Hyderabad,India. 1H NMR spectra were recorded on JEOL 100,270 and 500 MHz instruments at the University ofHyderabad, IISc, Bangalore and TIFR, Bombayrespectively. IR spectra in the region 100-600 em - 1

were recorded on a PE 983 spectrophotometer atRSIC, lIT, Madras, India. A digisun digitalconductivity meter No. 01909 was used to measurethe conductivities of the complexes in OMSOjwater.The physical, analytical and conductivity data of thecomplexes are given in Table 1.

The mixed ligand complexes (chloro)(adenine)-

KHAN et al.: MIXED LIGAND COMPLEXES OF Pd(II) & Pt(I) 107

Table I-Analytical and conductivity data of Pd(II) & Pt(II)-methionine-purine mixed ligand complexes

Complex Complex (Colour) Found (Calc.), % Molar conductivityNo. (mho cm? mol"I)

~C H Cl N

[Pd(MetH)C12] 465 (H2O)(Yellow) 2 (DMSO)

2 [Pt(MetH)CI2] 404 (H2O)(Yellow) 10 (DMSO)

3 [Pd(MetH)(Ade)CljCI.2Hp 24.67 3.98 16.64 320 (H2O)(Yellow) (24.12) (4.04) (16.87) 36 (DMSO)

4 [Pt(MetH)(Ade)CI]CI 21.60 2.42 13.20 310 (H2O)(Pale yellow) (21.71) (2.03) (12.88)•

5 [Pd(MetH)(Gua)CI]C1.2H2O 23.70 4.20 350 (HP)(Yellow) (23.37) (3.92)

6 [Pt(MetH)(Gua)CI]CI 21.35 2.62 12.83 318 (H2O)(Yellow) (21.18) (2.84) (12.52)

7 [Pd(MetH)(Hypo)CI]CI.H2O 24.60 3.37 13.96 326 (H2O)(Pale yellow) (24.98) (3.56) (14.56) 32 (DMSO)

8 [Pt(MetH)(Hypo)Cl]CI.H2O 21.32 2.30 12.70 295 (H2O)(Pale yellow) (21.07) (2.48) (12.45)

(methionine)palladium(II) chloride dihydrate (3),(chloro Hadenine )(methionine )platinum(lI) chlo-ride (4), (chloro)(guanine)(methionine)(palladium)(II) chloride hydrate (5), (chloro )(guanine )(methio-nine )platinum(ll) chloride (6), (chI oro )(hypoxan-1h ine)( methionine )palladi um( II) chloride mono-hydra tc (7) and (chloro )(hypoxanthine )(methio-nine)platinum(lI) chloride monohydrate (8) wereprepared by reacting fis-( dichloro )(methionine)-palladium( II) (1) or cis-( dichloro )(methionine)-platinum(lI) (2) with adenine/guanine/hypoxan-thine in a I: I mole ratio in aqueous medium. When thepurine was added to 1or 2 and the contents heated on awater bath for 0.5-3.0 hr, the colour of the solutionchanged from yellow to light yellow. The reactionmixtures were cooled and filtered to removeunreacted traces of the parent complex and the ligand.The solution was further concentrated when paleyellow complexes 3-8 were precipitated which werewashed with ethanol and dried with ether; yield,70%.

Results and DiscussionThe analytical data of the complexes (Table 1) are in

agreement with the stoichiometries proposed for thecomplexes. The infrared spectra of the parentcomplexes cis-[Pd(MetH)CI2l and cis-[Pt(MetH)Chlshow strong peaks at 1705 and 1710 em - 1

respectively, which are characteristic of theuncoordinated carboxylic acid group ofmethionine->. Due to the hydrogen bondinginteractions in these complexes, broad peaks were

observed in the region 3000-3245 em - 1. In the far IRregion, peaks were observed at 570-592 em - I whichare assigned to vM ~ N mode arising due 10 thecoordination of methionine to Pdt ll) or Pt(II)through amino nitrogen. Peaks observed in the region485-505 em - I arc assigned to vM ~ S which indicatecoordination of ether sulphur atom of methionine. Thetwo absorptions in the region 320-395 ern - I arecharacteristic of cis configurations for the chloroligands. These assignments are in agreement with thecoordination mode of methionine with PtOI)established by Freeman et al.23.24.

The ligand adenine shows vC:':': N + vC..:.:C at1335-1460 em - I while guanine and hypoxanthineshowpeaksduetovC=N+vC=Cat 151Ocm-1 and1600 em - I respectively in their IR spectra. In all themixed ligand complexes these peaks were shifted tolower frequencies indicating the involvement of oneof the ring nitrogens in coordination to the metalion-".

In the IR spectra of the complexes 3-6 strong andbroad peaks occurring in the region 1600-1710 em - I

are assigned to vC =0 of the uncoordinatedcarboxylic acid group and NHl deformation modesof adenine and guanine which overlap with eachother. The NHl groups of adenine and guanine do notparticipate in bonding to the metal ion under normalconditions, because the electron pair present on thenitrogen of the NH2 is de localized into the ringx-system and is not available for donation-".

In the far IR spectra of mixed ligand complexes theyM ~ N frequencies that arise due to the coordination

108 INDIAN J CHEM. SEe. A. FEBRUARY 1992

or methionine and purines are observed in the range507-585 ern - I. The peaks observed in the range417-490 ern - I are assigned to vM - S. In all the mixedligand complexes. a single peak observed in the rangeJ IS-J70 em" I is assigned to the vM - CI whichindicates that only one chloride is present in thecoordination sphere of the metal ion.

The electronic spectra of the complexes 3, 4, 5, 6, 7and 8 show peaks at 165 nrn (Erna, = 9.60 x 10ol).268 nm(£m,,\ = I.J8 x 1~).148 nm (Ern'" = 1.32 x IO~).274 nm(£m"\ = 4.86 x 103).150 nrn (10m", = 2.07 x IO~) and 255nm (10m", = 9.61 x 103). respectively which can beassigned to 11:-+11:* transitions of coordinated purine.The 11:-+11:* transitions occur in adenine at 268 nrn(Em'" = 1.13 x IO~) and 162 nm (£m", = 1.30 X 104).

Guanine and hypoxanthine show this transition at246 nrn (£m",=0.94x 10~) and 250 nrn(En"" = 1.05 X 10~) respectively.

The d-d transitions in Pd(lI) complexes areextremely weak with £ values less than 10. Therefore.they could not be recorded with reasonable accuracy.In Pt(lI) mixed ligand complexes weak d-dtransitionsoccur in the region 240-280 nm.

I n I H NM R spectrum of methionine a signal at 02.08 ppm is assigned to S - CH3 protons while a tripletcentered at () 2.60 ppm is due to the methylene pro-tons of the methionine. The proton present on thea-carbon atom of the methionine gives a signal at 03.JO ppm.

In the 'H NMR spectra of complexes I and 2, asinglet at 0 2.48 and a multiplet centered at 0 2.54 ppmare assigned to S - CH~ protons. The down field shiftof the signal by 0.4 ppm and 0.46 ppm, respectively inthese complexes indicates the involvement of sulphurin coordination to the metal ion. cis-[Pd(MetH)CI21showed peaks due to ~-CH2 and y-CH2 protons at 01.66 and 0 2.79 ppm, whereas the correspondingsignals merged in a peak at 2.80 ppm in cis-[Pt(MetH)CI21. Compared to uncoordinatedmethionine these signals are shifted downfield whichagain confirms the coordination ofS - CH~ group ofthe amino acid to the metal ion. The signal due to tX-CHproton occurs at 3.55 and 4.10 ppm observed in thespectra of these complexes, respectively can beassigned to ::t.-CH proton of methionine. These peaksare shifted downfield to the extent of 0.25 and 0.80ppm respectively in complexes 1 and 2 indicating thecoordination of NH2 group to the metal ion.

The IH NM R spectrum of adeni ne shows a doubletat 0 8.32 and 8.20 ppm due to CxH and C2H protons(see structure I). The IH NMR spectrum of complex 3shows a doublet at 8.46 and 8.40 ppm whereas incomplex 4 these peaks appear at 8.61 and 8.56 ppmrespectively. Since signals due to the C]H and C8H

••• Pd(II).r 1>1(11)

R,' ~Hl.R2·H Ad(nin<

R, :QH, R2 ': NH2" GuanineR, = OH. R2 = H Hypoltonihin(.

protons (see structure I) are shifted downfield incomplexes 3 and 4 by 0.14.0.20 and 0.29 and 0.36 ppmrespectively, it can be inferred that N7 or N, of adenineis involved in coordination in these cornplexes-". Inthe complex 3 the signals due to ::t.-CH. ~-CH2. y-CH2and S-CH, are observed as a triplet at 4.10, triplets ofdoublets centered at 2.53 and 2.46. a triplet at 2.68 anda singlet at 2.24 ppm respectively. These signals areobserved as a triplet centered at 4.28, triplets ofdoublets centered at 2.91 and 2.77, a triplet at 2.58 anda singlet at 2.31 ppm, respectively in complex 4. Thesignal due to the proton of o-carbon is observed as atriplet because of the spin-spin coupling with ~-CH2protons. The ~-CH2 protons show triplets of doubletdue to the spin-spin coupling with adjacent tX-CH andy-CH2 protons. The y-CH2 protons are observed as atriplet due to coupling with ~-CH2 protons. TheS - CH3 protons give a single peak.

The 1H NMR spectrum of guanine in D20 (basic)shows a signal at 7.68 ppm due to the CgH protons. Inthe IH NM R spectrum of complex 6, this signalappears at 8.78 ppm. Since this peak is shifteddownfield with respect to the ligand, N7 of the guanineis proposed as the binding site. The signals due tomethionine tX-CH, ~-CH2' y-CH2 and S-CH, protonsare observed in the region 4.21-2.51 ppm. The signaldue to the proton on the ex-carbon is observed at 4.21ppm. A triplet centered at 3.20 ppm is assigned to they-CH2 protons. A doublet appearing at 2.75 and 2.63ppm is assigned to ~-CH2 protons. The S-methylprotons are observed at 2.51 ppm.

The IH NMR spectrum of hypoxanthine exhibitstwo signals at 8.08 and 7.87 ppm respectively whichare assigned to CxH and C2H protons. The IH NMRspectrum of complex 7 shows these signals at 8.33 and7.75 respectively. Since signal due to CRH protons isshifted more, N7 of hypoxanthine is proposed as thecoordination site. In complex 8 these signals areobserved at 8.97 and 8.08 ppm respectively. As thesignal due to the 'CgH protons is shifted more (0.89ppm) in comparison to that due to C2H protons (0.21ppm), it is proposed that N7 ofhypoxanthine is thecoordination site in complex 8. The protons ofmethionine give peaks in the region 4.18-2.22 ppm

KHAN etal.: MIXED LIGAND COMPLEXES OF Pd(II) & Pt(I) 109

and 4.11-2.21 ppm respectively in complexes 7 and 8.Based on the above data a general structure (I) isproposed for complexes 3-8.

In all the complexes 1-8, both methionine andpurines bind to the metal ion, Pd(II) or Pt(II), throughsoft donor atoms sulphur and nitrogen, since bothmetal ions are soft acids-".

The reaction of purines with cis-[Pt(MetH)C12l andcis-[Pd(MetH)CI2l is very fast, as compared to thatwith cis-[Pt(GlyH)Chl, cis-[Pt(Ala)CI2l andK[Pt(His)CI2p6. This difference in the rates ofreaction is solely due to the high trans directing abilityof the coordinated sulphur group.

Since trans directing ability of coordinated sulphurin complexes 1and 2 is greater as compared to that ofcoordinated nitrogen, it is proposed that purine isoccupying a position trans to sulphur group of aminoacid eventhough one more site trans to amino group isalso available for the purine.

All these complexes show high molarconductivitiesin water, because of the ionization ofthe free COOH group in the complex. However, inDMSO some of these complexes show lowconductivities (below 40'mhos cm - 2 mol- J). On thebasis of the conductivity data and chloride estimationof a few complexes, it is proposed that all thecomplexes are 1:1 electrolytes.Acknowledgement

Two of us (KMM and GNG) are thankful to theCSIR, New Delhi for financial support to carry outthis work.References

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