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The preparation and spectroscopic characterization of some complexes of the type Bu2Sn(LH)2(LH= 5‐[(E)‐2‐(aryl)‐1‐diazenyl]‐2‐hydroxybenzoate) are reported. On the basis of spectroscopic evidence (1H, 13C, 119Sn NMR, IR and 119mSn Mössbauer) the compounds were judged to adopt the usual dicarboxylato structural type with a skew trapezoidal arrangement. This was further confirmed by X‐ray crystallography in the case of Bu2Sn(L5H)2(L5H = 5‐[(E)‐2‐(4‐chlorophenyl)‐1‐diazenyl]‐2‐hydroxybenzoate). Toxicity studies of the di‐ and tri‐organotin compounds on the second larval instar of Aedes aegyptimosquito larvae are reported. Copyright © 2003 John Wiley & Sons, Ltd.

New organotin(IV) derivatives with general formulae R2SnL, where R = n−Bu and L is the dianion of glycyltyrosine (H2L‐1), glycyltryptophane (H2L‐2), leucyltyrosine (H2L‐3), leucylleucine (H2L‐4), valylvaline (H2L‐5) and alanylvaline (H2L‐6) have been synthesized in 1 : 1 molar ratio by the reaction of Bu2SnO with the respective dipeptide under azeotropic removal of water. Triphenyltin glycylleucinate was obtained by reacting Ph3SnCl and sodium glycylleucinate with filtration of NaCl formed. The bonding and coordination behaviour in these derivatives are discussed on the basis of IR, multinuclear 1H, 13C and 117Sn magnetic resonance and 119Sn Mössbauer spectroscopic studies. These investigations suggest that all the ligands in R2SnL act as dianionic tridentates coordinating through the COO−, NH2and Npeptidegroups, whereas in Ph3Sn(HL) the ligand acts as a bidentate coordinating through the COO−and NH2groups. The 119Sn Mössbauer studies, together with the NMR data, indicate that, for the 1 : 1 monomeric derivatives, the polyhedron around tin in R2SnL is a trigonal bipyramid with the butyl groups and Npeptidein the equatorial positions, while the axial positions are occupied by a carboxylic oxygen and the amino nitrogen atom. In Ph3Sn(HL) the structure is intermediate between pseudotetrahedral and cis‐trigonal bipyramidal, with the Naminoand two phenyl groups in the equatorial plane and the carboxylate oxygen and the third phenyl group in axial positions. All the complexes have been screened against seven cancer cell lines of human origin, viz. MCF‐7, EVSA‐T, WiDr, IGROV, M19, MEL A498 and H226. Ph3Sn(HL) displays the lowest ID50values of the tin compounds tested and reported in this paper. Its activity is comparable to those of methotrexate and 5‐fluorouracil. All the di‐n‐butyltin compounds exhibit lower in vitroanti‐tumour activities than Ph3Sn(HL); however, they do provide significantly better activities than etoposide and cis‐platin. Copyright © 2003 John Wiley & Sons, Ltd.

New organotin(IV) derivatives with general formulae R2SnL, where R = n−Bu and L is the dianion of glycyltyrosine (H2L-1), glycyltryptophane (H2L-2), leucyltyrosine (H2L-3), leucylleucine (H2L-4), valylvaline (H2L-5) and alanylvaline (H2L-6) have been synthesized in 1 : 1 molar ratio by the reaction of Bu2SnO with the respective dipeptide under azeotropic removal of water. Triphenyltin glycylleucinate was obtained by reacting Ph3SnCl and sodium glycylleucinate with filtration of NaCl formed. The bonding and coordination behaviour in these derivatives are discussed on the basis of IR, multinuclear ¹H, ¹³C and ¹¹⁷Sn magnetic resonance and ¹¹⁹Sn Mössbauer spectroscopic studies. These investigations suggest that all the ligands in R2SnL act as dianionic tridentates coordinating through the COO⁻, NH2 and Npeptide groups, whereas in Ph3Sn(HL) the ligand acts as a bidentate coordinating through the COO⁻ and NH2 groups. The ¹¹⁹Sn Mössbauer studies, together with the NMR data, indicate that, for the 1 : 1 monomeric derivatives, the polyhedron around tin in R2SnL is a trigonal bipyramid with the butyl groups and Npeptide in the equatorial positions, while the axial positions are occupied by a carboxylic oxygen and the amino nitrogen atom. In Ph3Sn(HL) the structure is intermediate between pseudotetrahedral and cis-trigonal bipyramidal, with the Namino and two phenyl groups in the equatorial plane and the carboxylate oxygen and the third phenyl group in axial positions. All the complexes have been screened against seven cancer cell lines of human origin, viz. MCF-7, EVSA-T, WiDr, IGROV, M19, MEL A498 and H226. Ph3Sn(HL) displays the lowest ID50 values of the tin compounds tested and reported in this paper. Its activity is comparable to those of methotrexate and 5-fluorouracil. All the di-n-butyltin compounds exhibit lower in vitro anti-tumour activities than Ph3Sn(HL); however, they do provide significantly better activities than etoposide and cis-platin. Copyright © 2003 John Wiley & Sons, Ltd.

The preparation and spectroscopic characterization of some complexes of the type Bu2Sn(LH)2 (LH = 5-[(E)-2-(aryl)-1-diazenyl]-2-hydroxybenzoate) are reported. On the basis of spectroscopic evidence (¹H, ¹³C, ¹¹⁹Sn NMR, IR and ^119mSn Mössbauer) the compounds were judged to adopt the usual dicarboxylato structural type with a skew trapezoidal arrangement. This was further confirmed by X-ray crystallography in the case of Bu2Sn(L⁵H)2 (L⁵H = 5-[(E)-2-(4-chlorophenyl)-1-diazenyl]-2-hydroxybenzoate). Toxicity studies of the di- and tri-organotin compounds on the second larval instar of Aedes aegypti mosquito larvae are reported. Copyright © 2003 John Wiley & Sons, Ltd.

The effects of triorganotins on the 4th instar stage of Aedes aegyptilarvae were evaluated. The most effective of the 15 triorganotins used in the study was tributyltin chloride with an LC50value of 0.57 ± 0.07 mg dm−3. The low LC50values obtained indicated that this class of compounds is an effective larvicide against the larvae of this species of mosquito. The toxicity of the compounds was found to be primarily dependent on the R group attached to the tin atom. The order of activity for the triorganotins tested was Bu > Ph > Cy > Me. However, a limited order, based on two series of the compounds tested, was also observed for the anionic X group on the tin atom. Copyright ­© 2000 John Wiley & Sons, Ltd.

ABSTRACTTo understand the chemical basis of action for thePDR5-encoded multidrug resistance transporter ofSaccharomyces cerevisiae, we compared the relative hypersensitivities of the wild-type (RW2802) and null mutant strains toward a series of tri-n-alkyltin compounds. These compounds differ from each other in a systematic fashion—either by hydrocarbon chain length or by anion composition. Using zone-of-inhibition and fixed-concentration assays, we found that the ethyl, propyl, and butyl compounds are strong PDR5substrates, whereas the methyl and pentyl compounds are weak. We conclude that hydrophobicity and anion makeup are relatively unimportant factors in determining whether a tri-n-alkyltin compound is a good PDR5substrate but that the dissociation of the compound and the molecular size are significant.

Abstract: Triphenyltin compounds have been found to inhibit the growth ofCeratocystis ulmi, the fungal agent of Dutch elm disease. To determine where the tin compounds interacted with the fungus cell, tin Mssbauer spectra of the treated cells, cell walls, and cellular organelles were measured at 80K. The compounds examined included triphenyltin bromide, chloride, hydroxide, and iodide. The spectra of the whole cells were different from the spectra of the solid tin compounds and exhibited two major lines whose parameters were the same for all cells. This suggests that the tin compounds were bound to the cell as the triphenyltin cation. The same spectrum appears with cell-wall fraction, and a weak signal is present in the spectrum of treated cellular fractions. These results suggest that the tin compounds are bound to the cell walls.

The main mineral component of chrome ore that contains chromium is chromite. Certain legal and trade restrictions required the development of analytical techniques that would be useful in determining the country of origin of a chrome ore. Ores from 13 countries were examined by x-ray diffraction, x-ray fluorescence for chromium and iron content, and Mössbauer spectroscopy of iron sites. The 13 countries could be divided into four groups based on the chromium and iron content via x-ray fluorescence. The x-ray diffraction spectra could be used to identify the country of origin within three of the groups. Within the fourth group of countries, the x-ray diffraction spectra can be used to differentiate three subgroups, one of which includes only one country. Mössbauer spectroscopy is used to differentiate the countries within the remaining subgroups. A schema is presented for the identification of the ores from the 13 countries.

The gut microbiome plays an important role in human health and disease. Gnotobiotic animal and in vitrocell-based models provide some informative insights into mechanistic crosstalk. However, there is no existing system for a long-term co-culture of a human colonic mucosal barrier with super oxygen-sensitive commensal microbes, hindering the study of human-microbe interactions in a controlled manner.

Although the association between the microbiome and IBD and liver diseases is known, the cause and effect remain elusive. By connecting human microphysiological systems of the gut, liver, and circulating Treg and Th17 cells, we created a multi-organ model of ulcerative colitis (UC) ex vivo. The approach shows microbiome-derived short-chain fatty acids (SCFAs) to either improve or worsen UC severity, depending on the involvement of effector CD4 T cells. Using multiomics, we found SCFAs increased production of ketone bodies, glycolysis, and lipogenesis, while markedly reducing innate immune activation of the UC gut. However, during acute T cell-mediated inflammation, SCFAs exacerbated CD4+T cell-effector function, partially through metabolic reprograming, leading to gut barrier disruption and hepatic injury. These paradoxical findings underscore the emerging utility of human physiomimetic technology in combination with systems immunology to study causality and the fundamental entanglement of immunity, metabolism, and tissue homeostasis.

ß-catenin regulates cell–cell adhesion and maintains stemness through Wnt signalling, but how these functions are mechanistically related is not fully understood. A study now identifies CRAD as the mechanistic link, providing insight into how dysregulation of epithelial adhesion contributes to Wnt-driven tumorigenesis.

Background:Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with vascular hypoxia and abnormal platelet-endothelial adhesion. Hypoxia upregulates NEDD9 in tumor cells, and increased NEDD9 in human pulmonary artery endothelial cells (HPAECs) induces adverse vascular remodeling. We hypothesized that NEDD9 mediates platelet-endothelial adhesion to promote thrombosis in CTEPH.Methods:CTEPH endarterectomy specimens and CTEPH-HPAECs were used to profile NEDD9 ex vivo. Platelet-HPAEC adhesion was analyzed in vitrousing fluorescently-labeled platelets. Mass spectrometry and microscale thermophoresis sequenced NEDD9 and quantified NEDD9 protein-protein interactions, respectively. The results informed the development of a novel anti-NEDD9 monospecific antibody (msAb-N9). Adenosine diphosphate (ADP)-induced pulmonary arterial thrombosis and increased right ventricular systolic pressure (RVSP) were assessed in vivoin NEDD9-/-mice and msAb-N9-treated wild type (WT) mice.Results:Compared to normoxia, hypoxia increased HIF-1?-dependent NEDD9 significantly in HPAECs. In endarterectomy specimens, NEDD9 colocalized with P-Selectin, a platelet adhesion molecule that targets HPAECs, and NEDD9-P-Selectin binding was confirmed in vitro(KD=13.8 ? 11.3 nM). P-Selectin targeted a NEDD9 substrate domain peptide in the extracellular plasma membrane of HPAECs, and this sequence served as the msAb-N9 epitope. Compared to anti-IgG1control, msAb-N9 significantly inhibited platelet adhesion to HPAECs and CTEPH-HPAECs. Compared to controls, pulmonary arterial thrombosis was decreased by 65% (P<0.001) and 78% (P<0.001) in NEDD9-/-mice and msAb-N9-treated WT mice, respectively. Catheterization showed that pulmonary hypertension was also blunted in NEDD9-/-mice and msAb-N9 WT mice compared to controls (2.4 ? 2.3 vs. 2.2 ? 0.5 vs. 31 ? 9.5 vs. mmHg ? from baseline, P=0.03, N=6).Conclusions:Hypoxia promotes the formation of a NEDD9-P-Selectin complex, a novel molecular mechanism regulating platelet-HPAEC adhesion and pulmonary arterial thrombosis. Pharmacological antagonism of the NEDD9 substrate domain by msAb-N9 is a potential therapeutic with direct relevance to pulmonary thromboembolic disorders.

The crystal structures of two triorganotin butyrates were determined. Tricyclohexyltin 2-(p-chlorophenyl)-3-methylbutyrate was determined to have a distorted tetrahedral geometry. Trimethyltin 2-(p-chlorophenyl)-3-methylbutyrate, on the other hand, was found to be polymeric in nature with a trigonal bipyramidal configuration. The three methyl groups are located in the equatorial positions with the axial positions occupied by oxygen atoms from two different carboxylate groups. Copyright © 2003 John Wiley & Sons, Ltd.