Organometallic Complexes with Biological Molecules. XIV. Biological Activity of Dialkyl and Trialkyltin(IV) [Meso-tetra(4-carboxy- phenyl)porphinate] Derivatives C. Mansueto, 1 E. Puccia, 1 F. Maggio, 2 R. Di Stefano, 2 T. Fiore, 2 C. Pellerito, 2 F. Triolo 2 and L. Pellerito 2 * 1 Dipartimento di Biologia Animale, Universita ` di Palermo, Via Archirafi 18, 90123 Palermo, Italy 2 Dipartimento di Chimica Inorganica, Universita ` di Palermo, Viale delle Scienze, Parco d’Orleans, 90128 Palermo, Italy The effects of several organotin(IV) meso- tetra(4-carboxyphenyl)porphinate] derivatives with the general formula (R 2 Sn) 2 TPPC and (R 3 Sn) 4 TPPC (R = Me, Bu, Ph) were tested in vivo on ascidian embryonic development. Em- bryos at the two-cell stage were incubated in 1  10 5 or 1  10 7 M solutions of various compounds. The ligand, [meso-tetra(4-carboxy- phenyl)porphine] (H 4 TPPC) was toxic at 1  10 5 M, because development was blocked at an early gastrula stage, whereas 1  10 7 M H 4 TPPC allowed the eggs to develop up to the larva stage. The most toxic among the tested compounds was tributyltin(IV) [meso-tetra (4-carboxyphenyl)porphinate], (Bu 3 Sn) 4 TPPC, since the fertilized eggs were unable to divide into two cells, even at a concentration of 1  10 7 M. To correlate this embryonic arrest with the metabolic pathway, and especially to understand why cellular organelles first under- went chemical damage, 10 5 and 10 7 M (Bu 3 Sn) 4 TPPC-cultured fertilized eggs were tested for DNA, RNA, protein, glucose, lipid and ATP contents, comparing the values ob- tained with those of control culture fertilized egg contents. The higher concentration (1  10 5 M) reduced the content of all the tested compounds, but the lower one (1  10 7 M), even if still unable to allow cleavage, reduced only the lipids and the ATP contents. A hypothesis concerning initial damage to mitochondrial membrane is proposed. Copyright # 2000 John Wiley & Sons, Ltd. Keywords: organotin(IV); cytotoxicity; embyo- nic development; Ascidiaceae Received 6 April 1999; accepted 1 November 1999 INTRODUCTION The acute effects of organotin(IV) compounds, used as biocides on a number of organisms, have been extensively investigated. All these studies indicate that sublethal effects can have more serious long-term consequences in various processes which can ultimately affect the survival and propagation of the species. Therefore, there is considerable current interest in understanding the mechanism through which these compounds exert their toxic action on the organisms. It has been demonstrated that some of these derivatives are immunotoxic, neurotoxic, etc. 1 Moreover, they inhibit phagocy- tosis and exocytosis in the rat. 2 In Ciona intestina- lis, phagocytosis inhibition by tributyltin(IV) chloride (TBT) is irreversible, as demonstrated by Cooper et al. 3 TBT also affects the chromosome structure of Mollusca and Isopoda. 4,5 Furthermore, it is well known that organotin(IV) compounds may inhibit mitochondriae enzyme and hexokinase activity. 6,7 Developmental systems could be a suitable field of study because they share certain fundamental features, including: (1) storage and transfer of developmental in- formation, APPLIED ORGANOMETALLIC CHEMISTRY Appl. Organometal. Chem. 14, 229–235 (2000) Copyright # 2000 John Wiley & Sons, Ltd. * Correspondence to: Professor Lorenzo Pellerito, Dipartimento di Chimica Inorganica, Universita ` di Palermo, Viale delle Scienze, Parco d’Orleans, 90128 Palermo, Italy. E-mail: bioinorg@unipa.it Contract/grant sponsor: Ministero per l’Universita ´ e la Ricerca Scientifica e Tecnologica, Roma. Contract/grant sponsor: University of Palermo.