Indian Journal of Chemistry Vol. 41A, October 2002, pp. 2083-2087

Synthesis and characterization of mixed ligand complexes of Cu(II), Ni(II) and Co(II)

with cytidine and amino acids

P Rabindra Reddy* & A Mohan Reddy

Department of Chemistry, Osmania U ni versi ty, Hyderabad 500 007, India

Received 12 October 2000; revised 13 March 2002

The mixed ligand complexes of Cu(IJ), Ni(lJ) and Co(II) with cytidine and amino acids, L-alanine, L-phenylalanine and L-tryptophan have been synthesized and characterized by elemental analysis, conductivity, Infrared spectra, electronic spectral data and magnetic susceptibility measurements. In these complexes, the nucleoside acts as a monodentate ligand involving only N(3) in metal coordination whereas the amino acids acts as bidentate ligands coordinating through carboxylate oxygen and amino nitrogen. A distorted octahedral geometry for Cu(II), and octahedral geometries for both Ni(II) and Co(ll) was proposed.

Nucleic acids and proteins recognize each other by very specific and selective interactions through amino acid side chains and nucleic acid constitutents 1,2. Most of these reactions are mediated through a metal ion resulting in the formation of mixed ligand complexes3

.4. Study of these complexes has become important as they serve as models for many metalloenzyme reactions. Among the nucleic acid constituents-nucleosides-cytidine was considered simplest as far as its reactions with metals are concerned. However, even this nucleoside was found to exhibit the complex behaviour since the site of attachment is metal specific. Hard metal ions bind to C20 whereas soft to N(3) (ref. 5). Further, it was observed6 that cytidine shows discriminating tendencies towards stacking interactions, a phenomenon of biological significance. In this paper, we report the synthesis and characterization of mixed ligand complexes of Cu(II), Ni(II) and Co(Il) with cytidine and amino acids (L-alanine, L-phenylalanine and L-tryptophan). Based on elemental analysis, conductivity data, JR, magnetic susceptibility measurements and electronic spectra, the binding modes were assigned. Cytidine acts as a monodentate ligand with exclusive N(3) binding whereas the amino acids act as bidentate ligands coordinating through carboxylate oxygen and amino nitrogen. A distorted

E-mail : rabi_pr@hotmaol.com

octahedral geometry for Cu(I1) and octahedral geometries for both Ni(II) and Co(ll) was proposed.

Experimental The ligands cytidine (cyd), L-alanine (L-ala),

L-phenylalanine (L-phe) and L-tryptophan (L-trypt), were obtained from Sigma Chemical Company, USA. All the transition metal ions [Cu(II), Ni(IJ) and Co(II)] were of Analar grade (BDH). They were taken in the form of chlorides and were used as supplied. The IR spectra were recorded (in KBr discs) on the Shimadzu IR-435 and Perkin Elmer 1600 series FTIR in the region 4000-400 cm- 1 and far IR spectra in the region 800-200 cm-1 on Perkin Elmer 1430, spectrometers, respectively. The electronic spectra of the complexes were recorded in DMSO/H20 on Shimadzu UV -160A, Spectrophotometer. Conductivity measurements were performed using Digisun, Digital Conductivity Bridge (Model: Dl-909) and a dip type cell calibrated with KCI solution. The magnetic susceptibilities of the complexes were recorded on a Faraday balance (CAHN-7550-03) at room temperature using Hg[Co(CNS)4] as the standard. Elemental analyses were obtained from microanalytical Perkin Elmer 240C elemental analyser. The metal analyses were carried out on a AAS, Perkin Elmer 2380.

Synthesis of metal complexes

Complexes-i, 2 and 3 An aqueous solutions contaInIng 1.19 mmol of

L-alanine (L-ala) and 1.22 mmol cytidine (cyd), 1.18 mmol of L-phenylalanine (L-phe) and 1.20 mmol of cytidine (cyd), 1.17 mmol of L-tryptophan (L-trypt) and 1.17 mmol of cytidine (cyd) were added simultaneously to another aqueous solutions containing 1.19,l.l8,1.17 mmol of copper chloride. The above mixtures were refluxed on a heating mantle upto 20 h during which the colours of the solutions changed from blue to green (ppt not obtained). These green coloured solutions were further refluxed to another 10-12 h, when light brown coloured precipitates were obtained in green coloured solutions and when no further precipitation was noticed after couple of hours, the precipitates were filtered and washed with water to remove unreacted

2084 INDIAN J CHEM, SEC A, OCTOBER 2002

materials and impurities. After the complexation, the pH of the solutions was found to be 4-5. The purity of these compounds was established by TLC in a mixture of solvents of methanol-ethylacetate in 1:4 ratio.

Complexes-4, 5 alld 6 An equimolar (0.86 mmol) aqueous solutions of L­

alanine (L-ala) and cytidine (cyd), 0.84 mmol aqueous solutions of L-phenylalanine (L-phe) and cytidine (cyd), (0.84 mmol) aqueous solutions of L-tryptophan (L-trypt) and cytidine (cyd) were added simultaneously to another aqueous solutions containing 0.86,0.84,0.86 mmol of nickel ch loride. The above mixtures were refluxed on a heating mantle upto 30 h during which the colours of the solutions changed from green to yellow (ppt not obtained). These yellow coloured solutions were further refluxed to another 8-12 h when light brown coloured compounds were obtained in yellow coloured solutions and no further precipitation was noticed after couple of hours, the precipitates were filtered and washed with water to remove un reacted materials and impurities. After the complexation, the pH of the solutions was found to be between 5-6. The

purity of these compounds was established by TLC in a mixture of solvents of methanol-ethylacetate in 1:4 ratio.

Complexes-7, 8 and 9 An equimolar (1.28 mmol) aqueous solutions of L­

alanine (L-ala) and cytidine (cyd) ,an equimolar (0.44 mmol) aqueous solutions of L-phenylalanine (L-phe) and cytidine (cyd), an equimolar (0.85 mmol) aqueous solutions of L-tryptophan (L-trypt) and cytidine (cyd) were added simultaneously to another aqueous solutions containing 1.28,0.44,0.85 mmol of cobalt

chloride. The above mixtures were refluxed on a heating mantle upto 25 h during which the colour of the solutions were changed from pink to yellow (ppt not obtained). These yellow coloured solu tions were further refluxed to another 8-10 h when brown coloured compounds were obtained which were filtered and washed with water to remove unreacted materials and impurities . After the complexation, the pH of the solutions was found to be 5-6. The purity of these compounds was established by TLC in a mixture of solvents of methanol-ethyl acetate in 1:4 ratio.

Table I-Analyt ica l and conductivity data of mixed ligand complexes of Cu(I1), Ni(lI) and Co(lI) with cytidine and al11inoacids

SI. COl11plex Found (Calcd.)% 11M !lcrr 110 Carbon Hydrogen Nitrogen Metal ohl11- 'cl11- ' l11 ol- ' (M M) Temp. K

I. [Cu(cyd)(L-ala)(H10hCI] 30.16 4.49 11.28 13.02 002 1.98 [CuCI 2H2"N40~C I] (30.82) ( 4.92) ( 11.98) ( 13.58) (3.01)

2. [Cu( cyd)(L-pha)(H 20) 2CI] 39.01 4.54 10.89 11.12 004 2.21 [CuClsH27N404CI] (39 .75) (4.97) (10.31 ) ( 11.69) (3.01)

3. I Cu( cyd )(L-trypt)(HzO)lC1 J 40.58 4.73 11.24 10.03 071 2.68 [CuC20H10N,,01"C1 ] (39 .97) (4.99) ( 11.66) ( 10.58) (3 .01)

4. [Ni (cyd)(L-ala)(HzOhCI] 30.77 5.02 11 .05 12.76 074 3.27 [NiCI 2H2"N40IoJ CI (29 .97) (5.20) ( 11.65) ( 12.22) (3.01)

5. [Ni(cyd)(L-phe)(HzOhClj 40.86 4.92 10.71 10.28 002 3.07 [NiCl sH27N409CIJ (40.11) (5.01) (10.39) (10.89) (3.01)

6. [Ni(cyd)(L-trypt)(H2OhCIJ 41.02 4.64 12.03 10.56 004 3.35

[NiC2oH2sN,,014CIJ ( 41.55) ( 4.85 ) (12.12) (10. 16) (3.01)

7. [Co(cyd)(L-ala)(HzO)3C1 J 30.66 5.02 11.16 12.63 076 4.05

[CoC n H25N40 IOJ CI (29.96) (5.20) ( 11.65) ( 12.26) (3.01)

8. I Cot cyd)(L-phe )(H2O)lCI] 38.48 5.11 10.32 10. 14 082 3.98

[CoCl sH29N4010J CI (38.79) (5.21) (10.06) (10.58) (3.01)

9. [Cot cyd)(L-trypt)(HzOhCIJ 40.64 5.21 11.19 9.36 063 3.49 lCoC2oHloN5015J CI (40.28) (5.04) (11.75) (9.89) (3.01)

Free cytidine 3450 3550 1660 1605 [C9HLlNPs] (s) (s) (s) (s)

Free-alanine 3088 2950 1597(s) 1412(s) [C3H7NOz] (m) (m)

Free L-phenylalanine 3065 2956 1625(m) 141O(s) [C9H"NOz] (m) (m)

Free L-tryptophan 3033 2954 1665(s) 141O(s) [C IIH'2Nz0 2j (s) (m)

1. [Cu( cyd)(L-ala)(HzOhCI] 3444 3347 3188 2948 1674 1460 1535 1405 861 540 410 310 [CuC I2H2SN409Cl] (br) (br) (br) (br) (m) (m) (w) (s) (w) (br) (m) (w)

2. [Cu(cyd)(L-pha)(H2OhClj 3425 3341 3168 2931 1676 1460 1536 1392 861 560 41O(m) 305(s) [CuC,sH27N40 9Clj (br) (br) (br) (br) (w) (w) (w) (m) (w) (m) 345(m) Z

3. [Cu(cyd)(L-trypt)(H2OhClj 3490 3345 3130 2925 1676 1536 1645(sh) 1400 863 530(br) 41O(s) 0 >-3

[CuC20HwNsO,sCI] (s) (m) (m) (w) (s) (s) 1 620(sh) (s) (w) 590(br) 46O(s) trl en

4. [Ni(cyd)(L-ala)(H2OhCI] 3200- 3310 3125 2950 1651 1590 1496 1406 855 575 410 (NiC,zHzsN40 IO] CI 3450(br) (br) (br) (sh) (br) (br) (w) (m) (w) (m) (m)

5. [Ni(cyd)(L-phe)(H2OhCI] 3300- 3310 3164 2954 1655 1560 1495 1402 908 560 410 310 [NiC,sHn N40 9CI] 34oo(br) (br) (br) (br) (br) (sh) (w) (s) (w) (br) (br) (w)

6. [Ni(cyd)(L-trypt)(H2OhCI] 3300- 3330 3100 2930 1650 1580 1491 1409 867 560 425 310 [NiC20HzsNsO'4Cl] 34oo(br) (br) (br) (sh) (m) (br) (w) (s) (w) (br) (s) (w)

7. [Co(cyd)(L-ala)(HzOhClj 3300- 3300 3182 2945 1640-1680 1502 1560 1407 852 545 405 [CoCI2H2SN401O] Cl 3450(br) (br) (w) (br) (br) (w) (br) (w) (w) (br) (br)

8. [Co(cyd)(L-phe)(H2OhClj 3375 3108 2925 1631 1448 1495 1410 914 570(br) 490 [COC'SH29N40 lOj Cl (m) (w) (w) (m) (w) (m) (w) (w) 520(br) (m)

9. [Co( cyd)(L -trypt)(H2Oh CI] 3400 3330 3189 2931 1650 1501 1495 1411 867 550 420 [CoCzoH3oNsO,sl Cl (sh) (br) (br) (sh) (br) (w) (br) (w) (w) (br) (m)

2086 INDIAN J CHEM. SEC A. OCTOBER 2002

Results and discussion The analytical and conductivity data of the

complexes are presented in Table 1. The analytical data corresponds with 1: 1: 1 ratio of metal: Cyd:AA and two moles of water per mol of metal for complexes-I, 2, 5 and 6 and three moles of water for complexes-3, 4, 7, 8 and 9. The conductivity values in DMSO/H20 cOITespond to 1: 1 electrolytes for complexes-3, 4, 7, 8 and 9, while those for 1, 2, 5 and

7 6 the data suggests that they are non-electrolytes. The infrared spectra of various mixed ligand

complexes synthesised are compiled in Table 2. The infrared spectra of these mixed ligand complexes in comparison with free cytidine and respective free amino acids show characteristic band positions, band shifts and band intensities which can be correlated to monodentate cytidine binding and bidentate amino acids chelations. Metal binding through water molecules and chloride is also evidenced by the IR spectra8

-IO

. The characteristics of IR bands of free cytidine corresponding to uNHz anti-sym and -sym and uC=O are shown in the spectra of the complexes without any negative shifts, thus ruling out their participation in coordination. Nominal upward shifts in these vibrational frequencies are presumed to be the consequence of involvement of cytidine in coordination through different coordination sites, probably the azomethine nitrogen site. Considerable shifts in uC=N stretching frequencies, which corresponds to the N(3) of cytidine of all the metal complexes clearly indicate the involvement of N(3) of cytidine in metal coordination I 1-16 .

As regards chelation through amino acids, the IR spectra exhibit significant features in uNHz and uCOO- regions. It is worthwhile to mention here that free anUno acids exist as Zwitter ions (NH3.AA.COO-) and the IR spectra of these cannot be compared entirely with those of metal complexes as amino acids in metal complexes do not exist as Zwitter ions;

+ particularly free amino acids with N H3 functions

+ - I show uN H3 in the range of 3130-3030 cm . In the

+ complexes, N H3 gets deprotonated and binds to metal through neutral NH2 group. The transformation

+ of N H3 to NH2 must result in an upward shift in

uNH7 and free amino acids. At isoelectric point, they must -show uNH2 in the region 3500-3300 cm- I (refs 17 -18). In the present complexes, the IR spectra show characteristic bands in the region 3189-2925 cm -I,

which is lower in comparison with free uNHz. Hence, it can be concluded that nitrogen of the amino group is involved in coordination . The IR spectra show strong evidences in support of the involvement of carboxylate group in coordination. In comparison with free amino acids, the uCOO- (asy) shows positive shifts and uCOO- (sYIl1) record negative shifts, which are confirmatory evidences in support of monodenticitl. Thus, it may be concluded that amino acids behave as monobasic bidentates in these complexes involving amino nitrogen and carboxylate oxygen in coordination 17-ZZ. This spectra shows additional features which can be correlated with coordination through water molecules and chlorides as the spectra show broad strong band in the region 3500-3100 cm - I which broadly coincide with OH of water molecules. These broad bands show distinct structures, which correspond, to u-NHz of cytidine and amino acids as discussed earlier. The presence of coordinated water is further confirmed by non-ligand bands observed in the range 9 14-852 cm- I due to rocking mode of coordinated water. Other low intensity bands observed in far IR region, in the range 305-590 cm- I are due to u(M-Cl) , u(M-O) and u(M-N)9 stretchings. In complexes 3, 4, 7, 8 and 9, no evidence was found ' for the coordination of chloride IOn.

The magnetic data pertaining to these systems are given in Table l. The magnetic susceptibilities of Cu(II) complexes (1, 2 and 3) have magnetic moments l.98, 2.21 and 2.68 BM respectively, which

. d I 73 24 Th . account for one unpalre e ectron-·. e magnetic data of Ni(II) complexes (4, 5 and 6) show spin only magnetic moments of 3.27, 3.07 and 3.35 BM which

CI

l Stucture of [Co(Cyd) (L-trypt) ~)3 lCI

NOTES 2087

are in good agreement with the expected high spin octahedral d8 system with two unpaired electrons23,24, The observed magnetic moment values of CoOl) complexes (7, 8 and 9) of 4,05, 3,98 and 3,96 BM are an indication of high spin octahedral £ system with

. 2124 three unpaired electrons" .

The electronic spectral data of various complexes were recorded. The electronic spectra of cytidine shows an absorption band at 277.2 nm in DMSO which can be assigned to the n ~ n* transition of the free ligand. The electronic spectra of the complexes-I, 2 and 3 show multiple bands which are assigned to 2E~ ~ 2T2g, and CT transitions of cf system. Hence, a distorted octahedral geometry was considered for all the copper complexes24.26. The electronic spectra of the complexes-4, 5 and 6 show multiple bands which < • d 3 33 3( 3 are asslgne to A 2g ~ T2g, A2~ ~ T Ig F), A 2g ~

3TI g(P) and CT transitions of l ' system. Hence, an octahedral geometry was proposed for all the nickel complexes24.26. ' The electronic spectra of the complexes-7, 8 and 9 show multiple bands which are

. d4 4 44 44 asslgne to TI l! ~ T2g(F), T Ig ~ TI g(P) , T Ig ~ A2g and CT transitions of d7 system. Therefore, an octahedral geometry (Structure I) was proposed for all the cobalt complexs24.26

.

Acknowledgement The financial support from CSIR & DST, New

Delhi , is gratefully acknowledged.

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