Tin and Tin-Resistant Microorganisms in Chesapeake Bay

Sediment and water samples from nine stations in Chesapeake Bay were examined for tin content and for microbial populations resistant to inorganic tin (75 mg of Sn liter⁻¹ as SnCl₄·5H₂O) or to the organotin compound dimethyltin chloride [15 mg of Sn liter⁻¹ as (CH₃)₂SnCl₂]. Tin concentrations in sediments were higher (3.0 to 7.9 mg kg⁻¹) at sites impacted by human activity than at open water sites (0.8 to 0.9 mg kg⁻¹), and they were very high (239.6 mg kg⁻¹) in Baltimore Harbor, which is impacted by both shipping and heavy industry. Inorganic tin (75 mg Sn liter⁻¹) in agar medium significantly decreased viable counts, but its toxicity was markedly reduced in liquid medium; it was not toxic in medium solidified with silica gel. Addition of SnCl₄·5H₂O to these media produced a tin precipitate which was not involved in the metal's toxicity. The data suggest that a soluble tin-agar complex which is toxic to cells is formed in agar medium. Thus, the toxicity of tin depends more on the chemical species than on the metal concentration in the medium. All sites in Chesapeake Bay contained organisms resistant to tin. The microbial flora was more sensitive to (CH₃)₂SnCl₂ than to SnCl₄·5H₂O. The elevated level of tin-resistant microorganisms in some aeas not containing unusually high tin concentrations suggests that factors other than tin may participate in the selection for a tin-tolerant microbial flora.     

Comparison of tin and lead toxic action on erythropoietic system in blood and bone marrow of rabbits

The aim of this work was to assess and compare morphological changes in blood and bone marrow of rabbits afterper os (po) or intraperitoneal (ip) administration of equimolar doses of tin or lead. The experiment was performed on female rabbits that were divided into four groups of six animals each, and received stannous chloride SnCl₂×2 H₂O (Merck) or lead acetate Pb(CH₃COO)₂ (POCh Gliwice) in equimolar doses (ip—17/uM/kg) orper os (po—85/uM/kg). Group I was administered SnCl₂ ip at the dose of 2 mg Sn/kg every day for 3 mo, group II Pb(CH₃COO)₂ ip at a dose of 3.5 mg Pb/kg every day for 3 wk, group III po SnCl₂ (10 mg Sn/kg), and group IV po Pb(CH₃COO)₂ (17.5 mg Pb/kg), both for 4 mo. The morphological factors hemoglobin (Hb), hematocrit (Ht), erythrocyte (Ercs), and reticulocyte counts, MCV, MCH, MCHC, and erythropoietic system in bone marrow aspirates with sideroblast count, iron concentration, TIBC, and SI were estimated. Tin caused hemolytic anemia depending on abnormal iron utilization. After ip administration of tin, anemia was observed during the whole time of the study, whereas after po exposure, transient anemia was noticed. It has been proven that the mechanism of toxic action of tin on hematopoietic system is similar to the toxic effect of lead.     

Zingerone Protects Against Stannous Chloride-Induced and Hydrogen Peroxide-Induced Oxidative DNA Damage In Vitro

In this paper, we report the dose-dependent antioxidant activity and DNA protective effects of zingerone. At 500 μg/mL, the DPPH radical scavenging activity of zingerone and ascorbic acid as a standard was found to be 86.7 and 94.2 % respectively. At the same concentration, zingerone also showed significant reducing power (absorbance 0.471) compared to that of ascorbic acid (absorbance 0.394). The in vitro toxicity of stannous chloride (SnCl₂) was evaluated using genomic and plasmid DNA. SnCl₂-induced degradation of genomic DNA was found to occur at a concentration of 0.8 mM onwards with complete degradation at 1.02 mM and above. In the case of plasmid DNA, conversion of supercoiled DNA into the open circular form indicative of DNA nicking activity was observed at a concentration of 0.2 mM onwards; complete conversion was observed at a concentration of 1.02 mM and above. Zingerone was found to confer protection against SnCl₂-induced oxidative damage to genomic and plasmid DNA at concentrations of 500 and 750 μg/mL onwards, respectively. This protective effect was further confirmed in the presence of UV/H₂O₂-a known reactive oxygen species (ROS) generating system-wherein protection by zingerone against ROS-mediated DNA damage was observed at a concentration of 250 μg/mL onwards in a dose-dependent manner. This study clearly indicated the in vitro DNA protective property of zingerone against SnCl₂-induced, ROS-mediated DNA damage.     

Effects on Myzus persicae (Sulz.) and transmission of beet yellows virus of applying certain trace elements to sugar beet

Applications of lithium chloride (LiCl), zinc sulphate (ZnSO₄) or nickel sulphate (NiSO₄) to the roots of sugar-beet plants in the glasshouse encouraged settling on the leaves of adult apterae from a clone of Myzus persicae (Sulz.); conversely, treatment with boric acid (H₂B₂O₇) inhibited aphid settling. Larviposition of M. persicae was increased by NiSO₄ and tin chloride (SnCl₂). Viruliferous M. persicae transmitted beet yellows virus (BYV) more efficiently to plants treated with LiCl or H₂B₂O₇ than to those treated with copper sulphate (CuSO₄), ZnSO₄ or SnCl₂. The sulphate and chloride anions of the applied chemicals appeared to have little effect on M. persicae and virus transmission. It is suggested that applications of trace elements to sugar beet affected M. persicae and virus transmission by changing the concentrations of trace elements in the aphids' diet and by altering the metabolism of the leaf tissues in the host plant.     

Efficient Nanostructured TiO2/SnS Heterojunction Solar Cells

Tin sulfide (SnS) is one of the most promising solar cell materials, as it is abundant, environment friendly, available at low cost, and offers long‐term stability. However, the highest efficiency of the SnS solar cell reported so far remains at 4.36% even using the expensive atomic layer deposition process. This study reports on the fabrication of SnS solar cells by a solution process that employs rapid thermal treatment for few seconds under Ar gas flow after spin‐coating a precursor solution of SnCl₂ and thiourea dissolved in dimethylformamide onto a nanostructured thin TiO₂ electrode. The best‐performing cell exhibits power conversion efficiency (PCE) of 3.8% under 1 sun radiation conditions (AM1.5G). Moreover, secondary treatment using SnCl₂ results in a significant improvement of 4.8% in PCE, which is one of the highest efficiencies among SnS‐based solar cells, especially with TiO₂ electrodes. The thin film properties of SnS after SnCl₂ secondary treatment are analyzed using grazing‐incidence wide‐angle X‐ray scattering, and high‐resolution transmittance electron microscopy.     

Interaction of stannous chloride leads to alteration in DNA, triphosphate nucleotides and isolated bases

Stannous chloride (SnCl₂) is a reducing chemical agent used in several man-made products. SnCl₂ can generate reactive oxygen species (ROS); therefore, studies have been carried out in order to better understand its damaging action in biological systems. In this work, calf thymus DNA, triphosphate nucleotides and isolated bases were incubated with SnCl₂ and the results were analyzed through UV spectrophotometry. The presence of stannous ions altered the absorption spectra of all three isolates. The amount of stannous ions associated to DNA was measured by atomic absorption spectrophotometry. Data showed that more than 40% of the initial SnCl₂ concentration was present in the samples. Our results are in accordance with the damaging potential of this salt and present evidence that stannous ions can complex with DNA, inducing ROS in its vicinity, which may be responsible for the observed lesions. (Mol Cell Biochem xxx: 173–179, 2005)     

Adaptation to Cd(II) and Zn(II), and the caffeine-potentiated override of the G2 block induced by the checkpoint activated by DNA damage

ABSTRACT

Moderate and low concentrations of Zn(II) and Cd(II) were defined as those which depressed the rate of root elongation in Allium cepa L. to about 40 and 70% respectively of the control (17.3 ± 4.9 mm/day) at 25°C. At moderate concentrations, cells were detoxified from Cd(II), but not from Zn(II), by inducing the heavy metal chelators phytochelatins. Thus, root elongation further decreased (from 41 to 19% of the control) at moderate (0.05 mM) Cd(II) concentration upon addition of 0.25 mM L-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of phytochelatin synthesis. On the other hand, cells were also detoxified from Zn(II) by an alternative mechanism, as the 42% inhibition displayed at 0.5 mM Zn(II) concentration was partially reversed (up to 79%) in the presence of BSO. Zn(II) activated the checkpoint pathway induced by DNA damage, as a transient G₂ block was produced; this block was partially cancelled by caffeine, so that chromosomal bridges (but no breaks) were observed in ana-telophase. On the other hand, Cd(II) did not activate the DNA damage checkpoint, as cells entered into anaphase with chromosomal breaks and bridges without any delay. Cd(II) may preclude the recognition of DNA damage by altering protein-DNA interactions, since 30% of the metaphases displayed clumped chromosomes. A minimum threshold was required to induce the adaptive responses described here, as BSO did not modify the reduction in root elongation rate recorded at low concentrations of both heavy metals.     

Tin and iron halogenides as additives in ruthenium-catalyzed olefin metathesis

Different metal halogenides were used as additives in metathesis of 1-octene or in several cross-metathesis reactions catalysed by first and second generation Grubbs catalyst, 1 and 2, as well as by an improved first generation-type Grubbs catalyst 3. Tin(II) chloride and bromide enhance the performance of 1 and 3. The influence on 2 is rather minor under the chosen reaction conditions. The addition of iron(II) chloride and bromide results in an improvement of 1 to a lesser extent as the tin salts. The frequently observed isomerisation of olefins in metathesis reactions catalysed by 1 is suppressed in the presence of the applied tin salts.     

Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin

Quercetin has been reported to have carcinogenic effects. However, both quercetin and luteolin have anti-cancer activity. To clarify the mechanism underlying the carcinogenic effects of quercetin, we compared DNA damage occurring during apoptosis induced by quercetin with that occuring during apoptosis induced by luteolin. Both quercetin and luteolin similarly induced DNA cleavage with subsequent DNA ladder formation, characteristics of apoptosis, in HL-60 cells. In HP 100 cells, an H₂O₂-resistant clone of HL-60 cells, the extent of DNA cleavage and DNA ladder formation induced by quercetin was less than that in HL-60 cells, whereas differences between the two cell types were minimal after treatment with luteolin. In addition, quercetin increased the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), an indicator of oxidative DNA damage, in HL-60 cells but not in HP 100 cells. Luteolin did not increase 8-oxodG formation, but inhibited topoisomerase II (topo II) activity of nuclear extract more strongly than quercetin and cleaved DNA by forming a luteolin-topo II-DNA ternary complex. These results suggest that quercetin induces H₂O₂-mediated DNA damage, resulting in apoptosis or mutations, whereas luteolin induces apoptosis via topo II-mediated DNA cleavage. The H₂O₂-mediated DNA damage may be related to the carcinogenic effects of quercetin.     

Disturbances in heme biosynthesis in rabbits after administrationper os of low doses of tin or lead

The experiment was performed on female rabbits that receivedper os equimolar doses (17 μM Me/kg) of SnCl₂×2H₂O or Pb (CH₃ COO)₂ every day for 5 d. The activity of δ-aminolevulinic acid dehydratase (ALA-D) in the whole blood, liver, kidneys, brain, spleen, and bone marrow, concentration of free erythrocyte protoporphyrins (FEP), activity of δ-aminolevulinic acid synthetase (ALA-S) in the liver and bone marrow, urine δ-aminolevulinic acid (ALA-U), and coproporphyrins (CP-U) were determined. Lead and tin concentrations in the blood were estimated. Lead caused a significant inhibition of ALA-D in the blood, increased FEP concentration, and ALA and CP excretion in urine of rabbits. Lead also decreased ALA-D activity in the bone marrow and in the liver, and did not change ALA-2 activity in the liver and bone marrow. Tin did not change any of the examined indices. Tin doses applied in the present study, maintained within the limits of permissible standards of metal levels in human diet, did not affect the process of heme biosynthesis in rabbits.     

Structural,infrared and Mössbauer studies of octahedral cis-dichlorobis(diketonate)tin(IV) complexes having anti-tumour activity

Two complexes, SnCl₂(bzac)₂ [Hbzac = benzoylacetone] and SnCl₂(bzbz)₂ [Hbzbz = dibenzoylmethane], have been prepared and characterised by analytical, infrared and Mössbauer studies. In addition, the X-ray crystal structure of SnCl₂(bzbz)₂ has been determined. The crystals are orthorhombic, space group Pbca with cell parameters a=18.767(9), b=17.611(8), c=16.563(8) Å. A total of 2116 reflections with I/σ(I)⩾3 gave R=3.0%. The tin is coordinated to two cis-chlorine and four oxygen atoms from the dibenzoylmethanato ligands in an approximately octahedral arrangement. The bond distances in the tin coordination sphere are SnCl 2.335(2) and 2.344(2) Å and SnO 2.062(4), 2.074(4), 2.063(4) and 2.063(4) Å and the ClSnCl angle is 95.1(1)°. The results of anti-tumour tests on these complexes are given and attempts are made to correlate the anti-tumour activity of SnCl₂(bzbz)₂ with its structure.     

Synthesis and structures of three,four, and six-coordinate monomeric tin(II) and tin(IV) compounds containing η2-ketiminate ligands

A series of Sn(II) and Sn(IV) compounds containing ketiminate ligands were synthesized. Reactions of SnCl₂ with 1 or 2 equiv. Li[OCMeCHCMeNAr] (where Ar = 2,6-diisopropylphenyl) generate [OCMeCHCMeNAr]SnCl (1) and [OCMeCHCMeNAr]₂Sn (2) in moderate yield, respectively. Similarly, reacting SnCl₄ with 2 equiv. Li[OCMeCHCMeNAr] yields a six-coordinated [OCMeCHCMeNAr]₂SnCl₂ (3). Divalent tin compound 2 can be oxidized with I₂ in diethyl ether to generate tetravalent tin compound [OCMeCHCMeNAr]₂SnI₂ (4) in moderate yield. Compounds 1–4 have been characterized by ¹H and ¹³C NMR spectroscopy and have been analyzed by X-ray crystallography. Theoretical calculation found that the bonding of ketiminate ligands and tin atom in compound 2 has a strong ionic character.     

Copper-dependent DNA damage induced by hydrazobenzene,an azobenzene metabolite

Hydrazobenzene is carcinogenic to rats and mice and azobenzene is carcinogenic to rats. Hydrazobenzene is a metabolic intermediate of azobenzene. To clarify the mechanism of carcinogenesis by azobenzene and hydrazobenzene, we investigated DNA damage induced by hydrazobenzene, using ³²P-5′-end-labeled DNA fragments obtained from the c-Ha-ras-1 proto-oncogene and the p53 tumor suppressor gene. Hydrazobenzene caused DNA damage in the presence of Cu(II). Piperidine treatment enhanced the DNA damage greatly, suggesting that hydrazobenzene caused base modification and liberation. However, azobenzene did not cause DNA damage even in the presence of Cu(II). Hydrazobenzene plus Cu(II) caused DNA damage frequently at thymine residues. Catalase and a Cu(I)-specific chelator inhibited Cu(II)-mediated DNA damage by hydrazobenzene. Typical ^·OH scavengers did not inhibit the DNA damage. The main active species is probably a metal oxygen complex, such as Cu(I)-OOH. Formation of 8-oxo-7, 8-dihydro-2′-deoxyguanosine was increased by hydrazobenzene in the presence of Cu(II). Oxygen consumption and UV-Visible spectroscopic measurements have shown that hydrazobenzene is autoxidized to azobenzene with H₂O₂ formation. It is considered that the metal-mediated DNA damage by hydrazobenzene through H₂O₂ generation may be relevant for the expression of carcinogenicity of azobenzene and hydrazobenzene.     

Mechanism of DNA Damage and Apoptosis Induced by Tetrahydropapaveroline, a Metabolite of Dopamine

Tetrahydropapaveroline (THP), a metabolite of dopamine, has been suspected to be associated with dopaminergic neurotoxicity of L-DOPA. THP induced apoptosis in human leukemia cell line HL-60 cells, but did not in its hydrogen peroxide (H₂O₂)-resistant clone HP100. THP-induced DNA ladder formation in HL-60 cells was inhibited by a metal chelator. THP induced damage to ³²P-labeled DNA fragments in the presence of metals. In the presence of Fe(III)EDTA, THP caused DNA damage at every nucleotide. The DNA damage was inhibited by free hydroxy radical (^·OH) scavengers and catalase, suggesting that the Fe(III)EDTA-mediated DNA damage is mainly due to ^·OH generation. In the presence of Cu(II), THP caused DNA damage mainly at T and G of 5′-TG-3′ sequence. The inhibitive effect of catalase and bathocuproine on Cu(II)-mediated DNA damage suggested that H₂O₂ and Cu(I) participate in the DNA damage. This study demonstrated that THP-induced apoptosis via reactive oxygen species generated from reaction of H₂O₂ and metals plays an important role in cytotoxicity of L-DOPA.     

Toxicity of organotins towards the marine yeastDebaryomyces hansenii

Of nine organotin compounds tested towards the marine yeastDebaryomyces hansenii, only triphenyltin chloride (Ph₃SnCl) and mono-, di-, and tributyltin chloride induced significant K⁺ release from cells which was symptomatic of viability loss. The general order of toxicity of the butylated compounds was tributyltin chloride (Bu₃SnCl) > monobutyltin chloride (BuSnCl₃) dibutyltin chloride (Bu₂SnCl₂). The overall toxicity of Ph₃SnCl was similar to BuSnCl₃. Release of K⁺ induced by butylated tin compounds or by Ph₃SnCl was strongly dependent on the external pH. Maximal toxicity occurred at pH 6.5 for Bu₃SnCl, BuSnCl₃, and Ph₃SnCl, whereas maximal toxicity of Bu₂SnCl₂ occurred at pH 5.0. Toxicity was decreased above or below these values. The toxicity of BuSnCl₃, Bu₃SnCl, and Ph₃SnCl was reduced at salinity levels approximating to sea water conditions. Prior growth ofD. hansenii in 3% (w/v) NaCl also resulted in reduced sensitivity to Bu₃SnCl as evidenced by a decreased rate and extent of K⁺ efflux. Bu₃SnCl-induced Na⁺ release from cells grown in the absence or presence of 3% (w/v) NaCl was low and similar in both cases. It appeared that the monovalent cation was important in the reduction of Bu₃SnCl toxicity since Na₂SO₄ had a similar protective effect as NaCl while CsCl completely prevented K⁺ efflux. Thus, the effects of external NaCl were related both to Na⁺ and to Cl^–. These results emphasize that cellular and environmental factors influence the toxic effects of organotins and suggests that these compounds may be more effective antimicrobial agents in some environmental niches than in others.     

Synthesis and x-ray crystal structure of a tin(IV) tetrahalide adduct with a crown ether

The polymeric structure of the complex, [SnCl₄(H₂O)₂]18-crown-6·2H₂O, prepared by the addition of a solution of SnCl₄ to 18-crown-6, has been determined by X-ray analysis. The structure has been solved by three-dimensional Patterson-Fourier synthesis to a conventional R-factor of 0.13, by using 1394 reflections with I>3σ(I). The crystals are monoclinic, with a = 15.753(3), b = 15.072(3), c = 12.209(4), β = 97.77°(1.0), z = 4, and space group P2_1/^a. The tin atom is octahedrally coordinated to four chlorine atoms and two water molecules in cis positions. A very complex network of hydrogen bonding links together the tin coordination octahedron, the two water hydration molecules, and the two crystallographically-different half crown-ethers.     

Synthesis, characterization, crystal structures and in vitro antistaphylococcal activity of organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine

New organotin(IV) complexes of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) with 1:1 and/or 1:2 stoichiometry were synthesized and investigated by X-ray diffraction, FT-IR and ¹¹⁹Sn Mössbauer in the solid state and by ¹H and ¹³C NMR spectroscopy, in solution. Moreover, the crystal and molecular structures of Et₂SnCl₂(dbtp)₂ and Ph₂SnCl₂(EtOH)₂(dptp)₂ are reported. The complexes contain hexacoordinated tin atoms: in Et₂SnCl₂(dbtp)₂ two 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine molecules coordinate classically the tin atom through N(3) atom and the coordination around the tin atom shows a skew trapezoidal structure with axial ethyl groups. In Ph₂SnCl₂(EtOH)₂(dptp)₂ two ethanol molecules coordinate tin through the oxygen atom and the 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the OH group of the ethanol moieties; Ph₂SnCl₂(EtOH)₂(dptp)₂ has an all-trans structure and the C-Sn-C fragment is linear. On the basis of Mössbauer data, the 1:2 diorganotin(IV) complexes are advanced to have the same structure of Et₂SnCl₂(dbtp)₂, while Me₂SnCl₂(dptp)₂ to have a regular all-trans octahedral structure. A distorted cis-R₂ trigonal bipyramidal structure is assigned to 1:1 diorganotin(IV) complexes. The in vitro antibacterial activities of the synthesized complexes have been tested against a group of reference pathogen micro-organisms and some of them resulted active with MIC values of 5 μg/mL, most of all against staphylococcal strains, which shows their inhibitory effect.     

Antagonistic effect of magnesium chloride on the nickel chloride–induced inhibition of DNA replication in chinese hamster ovary cells

The degree of inhibition of semiconservative DNA replication induced by nickel chloride (NiCl₂) was analyzed by radiolabeled-thymidine incorporation alone or with cesium chloride (CsCl) density gradient centrifugation. The onset and duration of this Ni²⁺-induced inhibition was time- and concentration- dependent, but the degree of inhibition was not. A maximal reduction in the rate of DNA synthesis was observed within the first hour of treatment with 2.5 mM NiCl₂, which was the highest noncytotoxic concentration utilized. After six hours, 500 μM and 1 mM as well as 2.5 mM NiCl₂ all produced the same 50% to 60% reduction in [³H]-thymidine incorporation into DNA. The inhibitory effect of nickel ions on DNA synthesis was reversible. The rate of DNA synthesis following a 500 μM or 1 mM NiCl₂ treatment began to increase after washout of nickel, but a six-hour exposure of cells to 2.5 mM NiCl₂ produced a sustained 50% to 60% suppression of DNA synthetic activity for at least 36 hours. At all concentrations of NiCl₂ used in this study, some inhibition of DNA synthesis persisted for at least 48 hours, but by 72 hours after treatment, the rate of [³H]-thymidine incorporation was actually 10% above the control. Examination of autoradiographic slides of cells treated with 2.5 mM NiCl₂ for six hours demonstrated a 60% reduction of silver grains, but there was no preferential reduction in the quantity of grains in the nucleolus or any other region. Cesium chloride density gradient analysis of the replication of nucleolar DNA in cells treated with 2.5 mM nickel supported the autoradiographic findings. The inhibitory effect of NiCl₂ on DNA replication was prevented by the addition of magnesium chloride (MgCl₂) to cells maintained in a simple salts/glucose medium (SGM). This effect did not appear to be due to an antagonism of the cellular uptake of nickel by Mg²⁺, since the maximally effective dose of Mg²⁺ reduced ⁶³Ni²⁺ uptake by no more than 25% while the inhibition of replication was completely reversed.     

Diorganotin(IV) N-acetyl-l-cysteinate complexes: Synthesis, solid state, solution phase, DFT and biological investigations

Diorganotin(IV) complexes of N-acetyl-l-cysteine (H₂NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have been synthesized and their solid and solution-phase structural configurations investigated by FTIR, Mössbauer, ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy. FTIR results suggested that in R₂Sn(IV)NAC (R = Me, Bu, Ph) complexes NAC²⁻ behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through ester-type carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From ¹¹⁹Sn Mössbauer spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R₂Sn(IV) trigonal bipyramidal configuration. In DMSO-d₆ solution, NMR spectroscopic data showed the coordination of one solvent molecule to tin atom, while the coordination mode of the ligand through the ester-type carboxylate and the deprotonated thiolate group was retained in solution. DFT (Density Functional Theory) study confirmed the proposed structures in solution phase as well as the determination of the most probable stable ring conformation. Biological investigations showed that Bu₂SnCl₂ and NAC2 induce loss of viability in HCC cells and only moderate effects in non-tumor Chang liver cells. NAC2 showed lower cytotoxic activity than Bu₂SnCl₂, suggesting that the binding with NAC²⁻ modulates the marked cytotoxic activity exerted by Bu₂SnCl₂. Therefore, these novel butyl derivatives could represent a new class of anticancer drugs.