Platinum Complexes with a Phosphino-Oxime/Oximate Ligand

The platinum(II) complex [PtCl2(COD)] (2; COD = 1,5- cyclooctadiene) reacted with 1 and 2 equiv. of 2-(diphenylphosphanyl) benzaldehyde oxime (1) to generate [PtCl2{¿2-(P,N)-2- Ph2PC6H4CH=NOH}] (3) and [Pt{¿2-(P,N)-2-Ph2PC6H4CH=NOH}2]- [Cl]2 (4), respectively. Deprotonation of the oxime hydroxyl group of 3 with Na2CO3 led to the selective formation of the dinuclear species (¿-O)-[PtCl{¿2-(P,N)-2-Ph2PC6H4CH=NO}]2 (5), while the related methylated derivative (¿-O)-[PtMe{¿2-(P,N)-2- Ph2PC6H4CH=NO}]2 (7) could be obtained from the direct reaction of [PtMe2(COD)] (6) with the phosphino-oxime ligand 1. In the case of 4, its treatment with Na2CO3 yielded complex [Pt({¿2-(P,N)-2-Ph2PC6H4CH=NO}2H)][Cl] (8), as a result of the deprotonation of only one of the OH groups of 4. On the other hand, contrary to what was observed with 6, no deprotonation of the oxime occurred in the reaction of [PtMe3I]4 (9) with 1, from which the mononuclear PtIV derivative fac-[PtIMe3{¿2-(P,N)- 2-Ph2PC6H4CH=NOH}] (10) was isolated. The solid-state structures of compounds 3, 4, 7 and 10 were determined by X-ray crystallography. In addition, the potential of all the synthesized complexes as catalysts for the dehydrogenative coupling of hydrosilanes with alcohols is also briefly discussed.Peer Reviewe

Synthesis and reactivity of cytotoxic platinum(II) complexes of bidentate oximes: a step towards the functionalization of bioactive complexes

Two new platinum(II) complexes bearing triphenylphosphine and bidentate oxime ligands [Pt(Cl)(PPh3){(κ2-N,O)-(1{C(R)=N(OH)-2(O)C10H6})}] (R = H, Me) were synthesized in good yields from trans-[PtCl(μ-Cl)(PPh3)]2. The structure of [Pt(Cl)(PPh3){(κ2-N,O)-(1{CH=N(OH)-2(O)C10H6})}] was determined by single-crystal X-ray diffraction. Both complexes showed good antiproliferative properties in vitro against HeLa, A2780, and A2780cis cancer cell lines. They reacted cleanly with alkylating agents in the presence of aqueous bases under phase-transfer catalysis conditions to afford the corresponding O-alkylation products [Pt(Cl)(PPh3){(κ2-N,O)-(1{HC=N(OR′)-2(O)C10H6})}] [R′ = CH2CH2Cl, CH2Ph, (CH2)4Br] in good yields

OPTIMIZATION OF MSW KERBSIDE SEPARATE COLLECTION SYSTEMS THROUGH A DECISION SUPPORT MODEL

The main aim of this study was to optimize a previous model of MSW kerbside separate collection system (“old model”) developed for communities up to 10,000 inhabitants. The “new model”, compared with the old one, is more precise and complete as well as it allows additional performances and has several automated parts. It allows inserting input data in an Excel spreadsheet, and returns the output information to evaluate and analyse in order to take the most appropriate decisions. The new developed model can be used as decision support tool to design a kerbside separate collection system: the designer can both interact with the model and evaluate the automatic simulations; the designer can choose the most suitable solution for the case study on the base of specific needs. The model can be used for statistical evaluations or design forecasts, to compare different solutions in order to find the sub-optimal “preferred” solution

Novel Oximato-Bridged Platinum(II) Di- and Trimer(s): Synthetic, Structural, and in Vitro Anticancer Activity Studies

Novel platinum complexes of trans geometry [PtCl₂{(<i>Z</i>)-R­(H)­CNOH}₂] [R = Me (<b>1</b>), Et (<b>3</b>)] and [PtCl₂{(<i>E</i>)-R­(H)­CNOH}­{(<i>Z</i>)-R­(H)­CNOH}] [R = Me (<b>2</b>), Et (<b>4</b>)] as well as the classic <i>trans</i>-[PtCl₂(R₂CNOH)₂] [R = Me, Et] were reacted with an equivalent amount of silver acetate in acetone solution at ambient temperature, resulting in formation of unprecedented head-to-tail-oriented oximato-bridged dimers [PtCl­{μ-(<i>Z</i>)-R­(H)­CNO}­{(<i>Z</i>)-R­(H)­CNOH}]₂ [R = Me (<b>5</b>), Et (<b>7</b>)], [PtCl­{μ-(<i>Z</i>)-R­(H)­CNO}­{(<i>E</i>)-R­(H)­CNOH}]₂ [R = Me (<b>6</b>), Et (<b>8</b>)], and [PtCl­(μ-R₂CNO)­(R₂CNOH)]₂ [R = Me (<b>9</b>), Et (<b>10</b>)], correspondingly. The dimeric species feature a unique six-membered diplatinacycle and represent the first example of oxime ligands coordinated to platinum via the oxygen atom. All complexes were characterized by elemental analyses, electrospray ionization mass spectrometry, IR and multinuclear (¹H, ¹³C, and ¹⁹⁵Pt) NMR spectroscopy, as well as X-ray diffraction in the cases of dimers <b>6</b> and <b>9</b>. Furthermore, the crystal and molecular structures of a trimeric oximato-bridged complex <b>11</b> comprising three platinum units connected in a chain way were established. The cytotoxicity of both dimers and the respective monomers was comparatively evaluated in three human cancer cell lines: cisplatin-sensitive CH1 cells as well as cisplatin-resistant SW480 and A549 cells, whereupon structure–activity relationships were drawn. Thus, it was found that dimerization results in a substantial (up to 7-fold) improvement of IC₅₀ values of (aldoxime)­Pt^II compounds, whereas for the analogous complexes featuring ketoxime ligands the reverse trend was observed. Remarkably, the novel dimers yielded no cross-resistance with cisplatin in SW480 cells, exhibiting up to 2-fold enhanced cytotoxicity in comparison with the CH1 cell line and thereby possessing a promising potential to overcome resistance toward platinum anticancer drugs. The latter point was also confirmed by investigating the potency of apoptosis induction in the case of one monomer as well as one dimer; the investigated complexes proved to be strong apoptotic agents which could induce cell death even in the cisplatin-resistant SW480 cell line

Novel Oximato-Bridged Platinum(II) Di- and Trimer(s): Synthetic, Structural, and in Vitro Anticancer Activity Studies

Novel platinum complexes of trans geometry [PtCl₂{(<i>Z</i>)-R­(H)­CNOH}₂] [R = Me (<b>1</b>), Et (<b>3</b>)] and [PtCl₂{(<i>E</i>)-R­(H)­CNOH}­{(<i>Z</i>)-R­(H)­CNOH}] [R = Me (<b>2</b>), Et (<b>4</b>)] as well as the classic <i>trans</i>-[PtCl₂(R₂CNOH)₂] [R = Me, Et] were reacted with an equivalent amount of silver acetate in acetone solution at ambient temperature, resulting in formation of unprecedented head-to-tail-oriented oximato-bridged dimers [PtCl­{μ-(<i>Z</i>)-R­(H)­CNO}­{(<i>Z</i>)-R­(H)­CNOH}]₂ [R = Me (<b>5</b>), Et (<b>7</b>)], [PtCl­{μ-(<i>Z</i>)-R­(H)­CNO}­{(<i>E</i>)-R­(H)­CNOH}]₂ [R = Me (<b>6</b>), Et (<b>8</b>)], and [PtCl­(μ-R₂CNO)­(R₂CNOH)]₂ [R = Me (<b>9</b>), Et (<b>10</b>)], correspondingly. The dimeric species feature a unique six-membered diplatinacycle and represent the first example of oxime ligands coordinated to platinum via the oxygen atom. All complexes were characterized by elemental analyses, electrospray ionization mass spectrometry, IR and multinuclear (¹H, ¹³C, and ¹⁹⁵Pt) NMR spectroscopy, as well as X-ray diffraction in the cases of dimers <b>6</b> and <b>9</b>. Furthermore, the crystal and molecular structures of a trimeric oximato-bridged complex <b>11</b> comprising three platinum units connected in a chain way were established. The cytotoxicity of both dimers and the respective monomers was comparatively evaluated in three human cancer cell lines: cisplatin-sensitive CH1 cells as well as cisplatin-resistant SW480 and A549 cells, whereupon structure–activity relationships were drawn. Thus, it was found that dimerization results in a substantial (up to 7-fold) improvement of IC₅₀ values of (aldoxime)­Pt^II compounds, whereas for the analogous complexes featuring ketoxime ligands the reverse trend was observed. Remarkably, the novel dimers yielded no cross-resistance with cisplatin in SW480 cells, exhibiting up to 2-fold enhanced cytotoxicity in comparison with the CH1 cell line and thereby possessing a promising potential to overcome resistance toward platinum anticancer drugs. The latter point was also confirmed by investigating the potency of apoptosis induction in the case of one monomer as well as one dimer; the investigated complexes proved to be strong apoptotic agents which could induce cell death even in the cisplatin-resistant SW480 cell line