Organotin Compounds: New Chemistry and Applications

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14

Bioorganotin

Chemistry:

Biological

Oxidation of Organotin Compounds

Downloaded by CORNELL UNIV on August 19, 2016 | http://pubs.acs.org Publication Date: June 1, 1976 | doi: 10.1021/ba-1976-0157.ch014

RICHARD H. FISH, E L L A C. KIMMEL, and JOHN E. CASIDA Pesticide Chemistry and Toxicology Laboratory, Department of Entomological Sciences, College of Natural Resources, University of California, Berkeley, Calif. 94720

Previous reports on the biological oxidation of organotin com­ pounds concluded that destannylation (carbon-tin bond cleav­ age—e.g., tetraalkyltin to tri and dialkyltin derivatives) was the overall consequence of this reaction. Recent studies using tributyltin acetate show that the primary biological oxidation reaction is in fact hydroxylation of carbon-hydrogen bonds that are α, β, γ, and δ to the tin atom. The lability of the major metabolites, the a and β carbon-hydroxylated products, was the reason previous workers concluded that destannyla­ tion was the major biological oxidation reaction. A free radi­ cal process is invoked to explain the predominance of β and the significant amount of a-carbon-hydroxylation in n-alkyltin compounds. Triphenyltin derivatives are not hydroxylated or destannylated in the monooxygenase enzyme system although in vivo studies with rats reveal destannylation products.

T

he increased use of organotin compounds has stimulated renewed interest in their biological fate. A perusal of the literature, however, reveals numerous reports on their biological properties but no definitive studies on their metabolic reactions (1,2,3,4,5). This review considers the progress and pros­ pects in understanding a particularly important metabolic reaction of alkyltin compounds—their biological oxidation. Monooxygenase Enzyme Systems A widely studied metabolic reaction of organic compounds is their biological oxidation, where the in vitro investigations are usually carried out with monooxygenases of mammalian liver [e.g., rat liver microsomal preparations with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the essential 197

Zuckerman; Organotin Compounds: New Chemistry and Applications Advances in Chemistry; American Chemical Society: Washington, DC, 1976.

198

ORGANOTIN COMPOUNDS:

NEW CHEMISTRY AND APPLICATIONS

cofactor]. These are generally cytochrome P-450-dependent monooxygenases which convert carbon-hydrogen to carbon-hydroxyl bonds (6). This monoox­ ygenase system activates oxygen in a two-electron reduction with an iron-porphyrin-oxygen complex playing a major role (Scheme I).

Fe

ι

I I

I

-RH

RH

RH

-ROH

+H+

Downloaded by CORNELL UNIV on August 19, 2016 | http://pubs.acs.org Publication Date: June 1, 1976 | doi: 10.1021/ba-1976-0157.ch014

+RH

3 +

+0,

-OH"

Fe 0 -" I 1 _R0H _

3 +

+ _

2

Fe

3 +

0

2

2

-"

+

~FeO, 1 RH _

-NT

*— RH Scheme I

Unlike most compounds metabolized by the microsomal monooxygenases, the organotin derivatives have a propensity to coordinate nonspecifically with various available heteroatoms (7). This works against the specificity needed for binding of the substrate molecule (RH) in proximity to the active iron-oxygen complex (6) (Scheme II).

XfX Fe

S

3 +

\ + RH

SH

/

Fe X

/

3 +

—RH

\

/

1- ^ N

/

-—-TTRIT)>-L«-

Low Spin

\ -

H i g h Spin Scheme I I

It is not surprising, therefore, to find that trialkyltin derivatives give low me­ tabolite yields (