CIS-DICHLORO-(BUTORPHANOL-N,O)-PALLADIUM (II) A NEW METAL COMPLEX OF MORPHINAN ALKALOID

 

H. Petříčková1, I. Císařová2, A. Jegorov3

 

1Department of Solid State Chemistry, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic, e-mail: petrickh@vscht.cz

2Department of Inorganic Chemistry, Charles University, Hlavova 8, 128 43 Prague 2, Czech Republic, e-mail: cisarova@natur.cuni.cz

3IVAX CR a.s., Research Unit, Branišovská 31, 370 05 České Budějovice, Czech Republic, e-mail: alexandr_jegorov@ivax-cz.com 

 

A new type of morphinan-Pd(II) complex (1:1) coordinated via tert.-amine and vicinal hydroxy group was prepared from cis-bis(acetonitril)dichloropalladium and butorphanol. The structure was characterized by single crystal X-ray diffraction and compared with crystal structures of butorphanol base and butorphanol hydrochloride.

Regardless morphinan alkaloids are known to retain traces of various heavy metals, the number of their coordination complexes, which were isolated in pure state, is relatively very limited. The presence of the strongly basic tert.-amino group, phenolic OH group, or occasionally some other O-donor group classify morphinan alkaloids among typical “hard” bases.1 In contrast to the expectation, however, simple N-coordinated or phenolate complexes of “hard” metals were apparently never described. On the other hand, several π-diene or η3-allyl complexes of Cr, Fe, Mo, Pd, and Pt were reported.2 Coordination ability of the free electron pair of nitrogen was demonstrated in Rh(I) complex with P,N-coordinated phosphite derivative of codeine.3

Cis-Dichloro-(Butorphanol-N,O)-palladium (II) was prepared from trans-bis(acetonitril) dichloropalladium and butorphanol  [(9R,11S,14S)-(-)-17-(cyclobutylmethyl)morphinan-3,14-diol], a morphinan derivative used as analgesic for acute pain management and for the treatment of migraine.4

The morphinan ligand retains the typical T shape found in the butorphanol hydrochloride and butorphanol base. Crystal structures of butorphanol hydrochloride and butorphanol base exhibit expected geometry and will be shown for comparison. The interatomic distances and bond angles in the morphinan moiety of morphinan-Pd(II) complex have not been appreciably affected by complexation.

Stability of such complex created by the ligand with typically “hard” base donor atoms and low valent “soft” acid is however, rather unexpected.

 

1         R. G. Pearson, J. Am. Chem. Soc., 1963, 85, 3533; R. G. Pearson, "Introduction to Hard and Soft Acids and Bases". Dowden, Hutchinson, Ross, Stroudsburg, 1973.

2         A. J. Birch, Aust. J. Chem., 1969, 22, 971; H. B. Arzeno, D. H. R. Barton, S. G. Davies, X. Lusinchi, B. Meunier and C. Pascard, Nouv. J. Chim., 1980, 4, 369; J. P. Macquet and A. L. Beuchamp, Acta Cryst., 1985, C41, 860; A. J. Birch, L. F. Kelly and A. J. Liepa, Tetrahedron Lett., 1985, 26, 501; V. N. Kalinin, I. L. Belyakova, V. V. Derunov, J. K. Park and H. Schmidhammer, Mendeleev Commun., 1995, 22; V. N. Kalinin, V. V. Derunov, L. Maat, J. K. Park and H. Schmidhammer, Mendeleev Commun., 1995, 222.

3         K. N. Gavrilov, A. V. Korostylev, O. G. Bondarev, A. I. Polosuknin and V. A. Davankov, J. Organometal. Chem., 1999, 585, 290.

4         N. I. Cherny, Drugs, 1996, 51, 713; J. C. Gillis, P. Benfield and K. L. Goa, Drugs, 1995, 50, 157; A. Jegorov, R. Sobotík, S. Pakhomova, J. Ondráček, J. Novotný, M. Hušák and B. Kratochvíl, Coll. Czech. Chem. Commun., 1994, 59, 1361.

 

This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic (research project No. CEZ: MSM 223100002) and by the Grant Agency of the Czech Republic (grants No. 203/00/D095, 203/02/0436, 203/99/M037, 203/01/0700).