Indian Journal of ChemistryVol. 23A, February 1984, pp. 166-168

Studies of Metal (II & III) Complexesof Arnebin-l t

P PAINULY, S B KATIt, S K BAJPAtt & J S TANDON*Medicinal Chemistry Division,

Central Drug Research Institute, Lucknow 226001Received 17 December 1982; revised and accepted 21 September 1983

Various metal(I1 & III) complexes of Arnebin-I have beenprepared and characterised on the basis of analytical, tR, electronicspectral and magnetic moment data. All the complexes have alsobeen evaluated for their anticancer and antianaphytactic activities.

Arnebia nobilis (Boraginaceae) yielded severalnaphthoquinones 1 - 3, of which arnebin-I i.e. 5, 8-dihydroxy-2-( l'-{3, (3-dimethylaryloxy-4' -methylpent-3-enyl)-1, 4-naphthoquinone exhibited a wide range ofbiological activities, viz. anticancer, antibacterial,antifungal, antipassive cutaneous anaphytactic andwound healing activities" - 6. However, severe toxicityof this compound restricted its use as an anticancerdrug. The broad spectrum of arnebin activity andprevious results of bio-pharmacological screening of alarge number of coordination complexes of variousmetals and ligands 7 - t z prompted us to assess arnebin

complexes against cancer and anti passive cutaneousanaphylaxis (PCA). So in this note, we report thesynthesis, characterization and a few bio-pharmaco-logical aspects of arnebin complexes with variousmetals.

Arnebin-l complexes were prepared by refluxing amixture of methanolic solutions of arnebin-l and themetal salt in 1: 1 and 2: 1 molar ratio, on a water-bathfor 1 hr with continued stirring. However, zinc(I1) andplatinum(II) complexes required 48 hr of refluxing, Thecontents in each case were allowed to stand overnightand the resulting complexes were filtered, washed withmethanol, water and ether successively. The complexeswere finally dried in vacuo over anhydrous CaClz.

Complexes were evaluated for their toxicity andantianaphytactic reaction in mice by the methodsdescribed earlier", Results of anticancer activity havebeen provided by the Department of Health andHuman Services, National Institute of Health, U.S.A.

Analytical and other physicochemical data havebeen summarised in Table 1.

Analytical results (Table I) suggest the molecularformulae M(L-2H).nHzO for the complexes ofbipositive metal ions and M(L-2H)X.nHzO for the

Table I-Analytical and Physicochemical Data of the Complexes

Molec. formula Found (Calc.), ~~, lieU vC=O vCO vM-O PeA(8.M.) (ester) (carbonyl) (ern -I) ::--~inhi-

C H M (ern I) (em -I) bitionC2IH2006CU.2H20 54.95 4.92 12.82 2.15 1710 1250 480 60

(5.89) (5.13) (13.59)C21H2006CO.2H20 52.00 5.16 11.69 4.95 1715 1620, 1530 450, 380 35

(54.04) (5.17) (12.79)C2IH,006Ni.2 H2O 52.00 5.16 12.01 5.85 1720 1530 460,380 55

(54.80) (5.17) (12.68)C,,H2006Fe.2H20 54.00 5.20 12.00 5.50 1720 1520 455,365 58

(54.79) (5.22) (12.14)C21H2006FeCI.H20 54.00 5.80 11.00 5.86 1710 1520 470,410, 52

(52.79) (4.61) (11.69) 300C2IH,006VO 56.40 4.78 11.03 1.80 1720 1530, 1520 460 38

(57.89) (4.59) (11.71)C2IH'OO6Cr(CH)COO).H,O 54.60 5.13 10.50 4.85 1710 1650, 1540 460,365 35

(55.53) (5.26) (10.46)C2IH,006Mn.2H20 55.70 5.47 10.81 5.80 1710 1540 440 39

(54.90) (5.29) (11.99)C21H,006Zn 58.45 4.27 14.12 Diamag- 1710 1520 450,380 44

(58.19) (4.61) (15.09) neticClIH2006PtCI2 38.93 3.64 24.69 Diamag- 1710 1750 450,385 30

(37.61) (3.58) (25.30) netic

tCDRI Communication No. 3244.tDepartment of Chemistry, Lucknow University, Lucknow.

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complexes of tripositive metal ions respectively whereM=Cu2+, Co2+, Ni2+, Fe2+, Fe3 + , V02+, Cr3+,

Mn2+, Zn2+ & Pt4+; L=ar.nebin-l; X=CI- orCH3COO- and n=O, 1,2.

I nfra red spectraAll IR spectra were recorded on a Perkin-Elmer

infracord-l77 instrument in cesium iodide in the range4000-200 em -1. An absorption band at 1710 em -1 inthe spectra of arnebin-I and metal complexes appeareddue to an ester carbonyl in the molecule (Table 1). Astrong band at 1620 em - 1 in the infra red spectrum ofarnebin-I due to vC = 0 mode shifts on complexationwith various metals to - 1530 cm-" 1 indicating thecoordination of ligand through carbonyl oxygen 13.14.

A band of varying intensity corresponding tocoordinated water, has been observed in the region3300-3450 em -I in all the complexes of arnebin exceptvanadium, zinc and platinum cornplex P'!". Thespectral bands around 450 em - 1 in all the complexeshave been assigned to vM-0 modes 17. The complexesof arnebin with chromic acetate exhibited a strongband at 1650cm - 1 and a weak band at 1330em - 1 dueto v••.•COO and VS COO vibrations respectively ofacetate ion. A negative shift of 70 em - 1 in VS COO andno change in Vas COO frequency confirm thecoordination of acetate ion as a monodentate ligand 17.

The solid state electronic (diffuse reflectance) spectraof the complexes were recorded on a Cary-l4-spectrophotometer in nujol.

The Cu(II) complex shows d-d bands at 610 and 750nm, which indicate an octahedral structure for thecomplex 1 8.

In the diffuse reflectance spectrum of cobalt(II)complex, the bands observed at 1050 and 480 nm areassigned to the transitions 4T19-+4T29 and 4T19(F)-+4TI9(P) respectively. The band at 440 nm has beenassigned to the transition 4TI9(F)-+4T29(F). Thesespectral bands and magnetic moment of 4.95 B.M.confirm the octahedral geometry for coba1t(II)complex 1 9.

For nickel(II) complex in octahedral symmetry,three bands due to the transitions 3A 2g-+ 3 T 29(vd, 3A 2g-+3 Al~(F) (v2) and 3A2g-+3Tlg(P) (v3) are expected.These transitions are observed in the spectrum of thepresent nickel(ll) complex at 990, 590 and 370nm. Thissuggests an octahedral structure for the complex?".

A weak band at 370 nm in the spectrum of theiron(ll) complex is attributed to n-+71* transition. Aband at 555nm with a shoulder at 495 nm is assigned toT2g-+71* transition which is responsible for the intensecolour of iron complex. The spectral data along withmagnetic moment of 5.50 B.M. indicate an octahedralstructure for the iron(Il) complex:".

NOTES

A magnetic moment value of 1.8 B.M. indicates thequadrivalent nature of the vanadium in the presentcomplex. Its electronic spectrum (in solid state) exhibitsa strong band at 800 nm and a weak band at 625 nmwhich may be assigned to b2(dx).)-+e(dx:, d).•) andb2(dx).)-+bddx2_).2) transitions respectively. Thespectral bands suggest a tettahedral symmetry for thevanadium complex+'.

The solid state electronic spectrum of chromium(III)complex exhibits three bands at 263, 405 and 585 nmassignable tothe transitions 4A2g(F)-+4T1g(P), 4TI9(F)and 4T2g(F) respectively.. These transitions suggestoctahedral structure for the chromium complex23•24.

In the Mn(ll) complex the colour results due to thepresence of charge-transfer bands in the region 470-580nm. In Mn(l1) complex no spin-allowed transitions areexpected. The nujol spectrum of the complex does notgive any well-defined band. However, a weak band hasbeen observed at 490 nm. The magnetic moment of 5.85B.M. suggested an octahedral structure for thiscomplex 1 8.

On the basis of poor solubilities of these complexesin most of the organic solvents and the abovementioned spectral data, a polymeric structure of type(I) may be proposed for all the complexes.

[0¢&>]°XP""M/2 n

(I)

Biological screeningData of toxicological investigations reveal that all

the metal complexes of arnebin-I are less toxic thanarnebin-I itself. However, Pt and Zn complexes arealmost non-toxic.

Arnebin-I is an active compound against Rat walkercarcinosarcoma 256, but its use as a drug is not safebecause of its severe toxicity (LDso = 12.5 mg/kg, i.p.).All the metal complexes of arnebin-l have also beenevaluated for their anticancer activity. Zioc(JI) andmanganese(II) complexes have been found to possesspronounced anticancer activity against LeukaemiaP388. Arnebin and an its metal complexes have beensubjected to anti passive cutaneous anaphylactic (PCA)reaction in mice by the method described earlier+!".Arnebin inhibited PCA reaction upto 90 per cent,whereas its metal complexes showed inhibition in therange 30-60 per cent. All these inhibition data wererecorded at a fixed dose of 10rug/kg, and 'azathioprine'and 'unital' served as reference standards forcomparison.

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INDIAN J. CHEM., VOL 23A, FEBRUARY 1984

One of us (P P) thanks the CSIR, New Delhi, for acost-doctoral fellowship.

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