Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood-brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187-297 nm, zeta potential values in the range of -4.1--9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.

Intercalative binding of two new five-coordinated anticancer Pt(II) complexes to DNA: experimental and computational approaches.

Binding interaction of two organoplatinum complexes, [Pt(C^N)Cl(dppa)], 1, and [Pt(C^N)Cl(dppm)], 2, (C^N = N(1), C(2')-chelated, deprotonated 2-phenylpyridine, dppa = bis(diphenylphosphino)amine, dppm = bis(diphenylphosphino)methane), as anti-tumor agents, with calf thymus DNA (CT-DNA) under pseudo-physiological conditions has been investigated using various biophysical techniques viz., UV-Vis and fluorescence spectroscopies, viscosity measurements, and thermal denaturation experiments. A hypochromic shift in UV-Vis absorption titration, fluorescence enhancement of Pt(II) complexes in the presence of CT-DNA, fluorescence quenching in competitive ethidium bromide displacement assay, and an uptrend in the viscosity (η) and melting temperature (Tm) indicated the existence of a tight intercalative interaction of Pt(II) complexes with CT-DNA. The fluorescence quenching of CT-DNA was a combined quenching of static and dynamic with Stern-Volmer quenching constants of 7.520 × 103 M-1 for complex 1 and 5.183 × 103 M-1 for complex 2, at low concentrations of Pt(II) complexes. Besides the experimental studies, computational studies were done. Molecular modeling studies confirmed the intercalation of the studied complexes by the phenyl groups of dppa and dppm, leading to π-π interactions but with a certain steric hindrance because of the size and shape of the considered complexes. The combination of experimental and computational data showed that reported Pt(II) complexes are promising structures and could be developed for cancer therapeutic applications.Communicated by Ramaswamy H. Sarma.

Affinity of two novel five-coordinated anticancer Pt(II) complexes to human and bovine serum albumins: a spectroscopic approach.

The interactions of two organoplatinum complexes, [Pt(C^N)Cl(dppa)], 1, and [Pt(C^N)Cl(dppm)], 2 (C^N = N(1), C(2')-chelated, deprotonated 2-phenylpyridine, dppa = bis(diphenylphosphino)amine, dppm = bis(diphenylphosphino)methane), as antitumor agents, with bovine serum albumin (BSA) and human serum albumin (HSA) have been studied by fluorescence and UV-vis absorption spectroscopic techniques at pH 7.40. The quenching constants and binding parameters (binding constants and number of binding sites) were determined by fluorescence quenching method. The obtained results revealed that there is a strong binding interaction between the ligands and proteins. The calculated thermodynamic parameters (ΔG, ΔH, and ΔS) confirmed that the binding reaction is mainly entropy-driven, and hydrophobic forces played a major role in the reaction. The displacement experiment shows that these Pt complexes can bind to the subdomain IIA (site I) of albumin. Moreover, synchronous fluorescence spectroscopy studies revealed some changes in the local polarity around the tryptophan residues. Finally, the distance, r, between donor (serum albumin) and acceptor (Pt complexes) was obtained according to Förster theory of nonradiation energy transfer.

The role of milk-derived exosomes in the treatment of diseases.

Exosomes (EXOs) are natural nanoparticles of endosome origin that are secreted by a variety of cells in the body. Exosomes have been found in bio-fluids such as urine, saliva, amniotic fluid, and ascites, among others. Milk is the only commercially available biological liquid containing EXOs. Proof that exosomes are essential for cell-to-cell communication is increasingly being reported. Studies have shown that they migrate from the cell of origin to various bioactive substances, including membrane receptors, proteins, mRNAs, microRNAs, and organelles, or they can stimulate target cells directly through interactions with receptors. Because of the presence of specific proteins, lipids, and RNAs, exosomes act in physiological and pathological conditions in vivo. Other salient features of EXOs include their long half-life in the body, no tumorigenesis, low immune response, good biocompatibility, ability to target cells through their surface biomarkers, and capacity to carry macromolecules. EXOs have been introduced to the scientific community as important, efficient, and attractive nanoparticles. They can be extracted from different sources and have the same characteristics as their parents. EXOs present in milk can be separated by size exclusion chromatography, density gradient centrifugation, or (ultra) centrifugation; however, the complex composition of milk that includes casein micelles and milk fat globules makes it necessary to take additional issues into consideration when employing the mentioned techniques with milk. As a rich source of EXOs, milk has unique properties that, in addition to its role as a carrier, promotes its use in treating diseases such as digestive problems, skin ulcers, and cancer, Moreover, EXOs derived from camel milk are reported to reduce the risk of oxidative stress and cancer. Milk-derived exosomes (MDEs) from yak milk improves gastrointestinal tract (GIT) development under hypoxic conditions. Furthermore, yak-MDEs have been suggested to be the best treatment for intestinal epithelial cells (IEC-6 cell line). Because of their availability as well as the non-invasiveness and cost-effectiveness of their preparation, isolates from mammals milk can be excellent resources for studies related to EXOs. These features also make it possible to exploit MDEs in clinical trials. The current study aimed to investigate the therapeutic applications of EXOs isolated from various milk sources.

Associative and dissociative mechanisms in the formation of phthalazine bridged organodiplatinum(II) complexes.

The reaction of phthalazine with the binuclear organoplatinum complexes [Me(2)Pt(µ-SMe(2))(µ-dppm)PtR(2)], R = Me, Ph, 4-tolyl or R(2) = (CH(2))(4), dppm = bis(diphenylphosphino)methane, gives the corresponding complexes [Me(2)Pt(µ-phthalazine)(µ-dppm)PtR(2)] by displacement of the bridging dimethylsulfide ligand. The structures of [Me(2)Pt(µ-SMe(2))(µ-dppm)PtMe(2)] and [Me(2)Pt(µ-phthalazine)(µ-dppm)PtMe(2)] have been determined. Kinetic studies show that the reactions occur mostly by a second order reaction when R = Me or R(2) = (CH(2))(4) but entirely by a first order reaction when R = Ph or 4-tolyl. Evidence is presented that the reactions when R = Me or R(2) = (CH(2))(4) can occur by either associative or dissociative mechanisms but that the reactions when R = Ph or 4-tolyl occur only by an unusual dissociative mechanism involving formation of an intermediate with a donor-acceptor Pt-Pt bond.

Cyclometalated cluster complex with a butterfly-shaped Pt2Ag2 core.

The cyclometalated platinum complex [PtMe(bhq)(dppy)] (1), in which bhq = benzo{h}quinoline and dppy = 2-(diphenylphosphino)pyridine, was prepared by the reaction of [PtMe(SMe(2))(bhq)] with 1 equiv of dppy at room temperature. Complex 1 contains one free pyridyl unit and was readily characterized by multinuclear NMR spectroscopy and elemental microanalysis. The reaction of complex 1 with 1 equiv of [Ag(CH(3)CN)(4)]BF(4) gave the cyclometalated cluster complex [Pt(2)Me(2)(bhq)(2)(mu-dppy)(2)Ag(2)(mu-acetone)](BF(4))(2) (2) in 70% yield. The crystal structure of complex 2 was determined by X-ray crystallography, indicating a rare example of a butterfly cluster with a Pt(2)Ag(2) core in which the Ag atoms occupy the edge-sharing bond. In solution, the bridging acetone dissociates from the cluster complex 2, but as shown by NMR spectroscopy, the Pt(2)Ag(2) core is retained in solution and a dynamic equilibrium is suggested to be established between the planar and butterfly skeletal geometries.

Anticancer activity assessment of two novel binuclear platinum (II) complexes.

In the current study, two binuclear Pt (II) complexes, containing cis, cis-[Me2Pt (µ-NN) (µ-dppm) PtMe2] (1), and cis,cis-[Me2Pt(µ-NN)(µ dppm) Pt((CH2)4)] (2) in which NN=phthalazine and dppm=bis (diphenylphosphino) methane were evaluated for their anticancer activities and DNA/purine nucleotide binding properties. These Pt (II) complexes, with the non-classical structures, demonstrated a significant anticancer activity against Jurkat and MCF-7 cancer cell lines. The results of ethidium bromide/acridine orange staining and Caspase-III activity suggest that these complexes were capable to stimulate an apoptotic mechanism of cell death in the cancer cells. Using different biophysical techniques and docking simulation analysis, we indicated that these complexes were also capable to interact efficiently with DNA via a non-intercalative mechanism. According to our results, substitution of cyclopentane (in complex 2) with two methyl groups (in complex 1) results in significant improvement of the complex ability to interact with DNA and subsequently to induce the anticancer activity. Overall, these binuclear Pt (II) complexes are promising group of the non-classical potential anticancer agents which can be considered as molecular templates in designing of highly efficient platinum anticancer drugs.

Luminescence properties of some monomeric and dimeric cycloplatinated(ii) complexes containing biphosphine ligands.

The starting complexes [PtCl(C^N)(dmso)], in which C^N is either ppy = 2-phenylpyridinate, , or bhq = 7,8-benzo[h]quinolinate, , were prepared by a known method using the reaction of [PtCl2(dmso)2] with ppyH or bhqH, respectively, in toluene under reflux conditions. The reaction of [PtCl(C^N)(dmso)], or , with 1 equiv. of a number of biphosphine ligands, P^P, gave the cationic monomeric complexes [Pt(ppy)(P^P)]Cl, for which P^P is either 1,2-bis(diphenylphosphino)ethane (dppe), , 1,3-bis(diphenylphosphino)propane (dppp), , or bis(diphenylphosphino)methane (dppm), ; the bhq analogous complex [Pt(bhq)(dppe)]Cl, , was prepared similarly. However, the complex [Pt(ppy)(dfppe)]Cl, , in which dfppe is 1,2-bis(dipentafluorophenylphosphino)ethane, was prepared by the reaction of with excess amount of dfppe. When each of the starting complexes [PtCl(C^N)(dmso)], or , were reacted with 0.5 equiv. of any of the P^P ligands, the dimeric complexes [Pt2Cl2(ppy)2(µ-P^P)], , or [Pt2Cl2(bhq)2(µ-P^P)], , were formed. The complexes were fully characterized using multinuclear ((1)H and (31)P) NMR spectroscopy and elemental analysis. The structures of typical complexes , , , and were also confirmed by X-ray crystallography. The effect of ligands on the luminescent properties of the complexes was investigated and DFT calculations were performed to confirm the assignments.

DNA binding and anticancer activity of novel cyclometalated platinum (II) complexes.

This study describes anticancer activity and DNA binding properties of two cyclometalated platinum (II) complexes with non-leaving lipophilic ligands; deprotonated 2-phenylpryidine (ppy): C1 and deprotonated benzo[h] quinolone (bhq): C2. Both complexes demonstrate significant anticancer activity and were capable to stimulate Caspase-III activity in Jurkat cancer cells. The results of Acridine orange/Ethidium bromide(AO/EtB), along with those of Caspase-III activity suggest that these complexes can induce apoptosis in the cancer cells. Moreover, C1 with flexible chemical structure indicates considerably higher anticancer activity than C2 which possesses a higher structural rigidity. Additionally, C2 represents a complex which is in part inducing cancer cell death due to the cell injury (necrosis). The absorption spectra of DNA demonstrate a hypochromic effect in the presence of increasing concentration of these complexes, reflecting DNA structural alteration after drug binding. Also, EtB competition assay and docking results revealed partial intercalation and DNA groove binding for the metal complexes. Overall, from the therapeutic point of view, ppy containing platinum complex (C1) is a favored anticancer agent, because it induces signaling cell death (apoptosis) in cancer cells, and lacks the necrotic effect.

The binding assessment with human serum albumin of novel six-coordinate Pt(IV) complexes, containing bidentate nitrogen donor/methyl ligands.

The interactions between platinum complexes and human serum albumin (HSA) play crucial roles in the distribution, metabolism, and activity of platinum-based anticancer drugs. Octahedral platinum (IV) complexes represent a significant class of anticancer agents that display molecular pharmacological properties different from cisplatin. In this study, the interaction between two Pt(IV) complexes with the general formula [Pt(X)2Me2 (tbu2bpy)], where tbu2bpy = 4,4'-ditert-butyl-2,2'-bipyridine, with two leaving groups of X = Cl (Com1) or Br (Com2), and HSA were investigated, using Ultraviolet-Visible (UV-Vis) spectroscopy, fluorescence spectroscopy, circular dichroism (CD) and molecular docking simulation. The spectroscopic and thermodynamic data revealed that the HSA/Pt(IV) complexes interactions were spontaneous process and Com2 demonstrated stronger interaction and binding constant in comparison with Com1. Also, the results suggest approximately similar structural alteration of HSA in the presence of these Pt complexes. Molecular docking revealed that both Pt(IV) complexes bind with HSA in subdomain IB, literally the same as each other. This study suggests that variation in the leaving group, displaying differing departure rate, has no significant contribution in denaturing prosperities of the Pt(IV) complexes against HSA.

DNA Binding and Anticancer Activity of Novel Cyclometalated Platinum (II) Complexes.

This study describes anticancer activity and DNA binding properties of two cyclometalated platinum (II) complexes with non-leaving lipophilic ligands; deperotonated 2-phenylpryidine (ppy): C1 and deperotonated benzo[h]quinolone (bhq): C2. Both complexes demonstrate significant anticancer activity and were capable to stimulate Caspase-III activity in Jurkat cancer cells. The results of Acridine orange/Ethidium bromide(AO/EtB), along with those of Caspase-III activity suggest that these complexes can induce apoptosis in the cancer cells. Moreover, C1 with flexible chemical structure indicates considerably higher anticancer activity than C2 which possesses a higher structural rigidity. Additionally, C2 represents a complex which is in part inducing cancer cell death due to the cell injury (necrosis). The absorption spectra of DNA demonstrate a hypochromic effect in the presence of increasing concentration of these complexes, reflecting DNA structural alteration after drug binding. Also, EtB competition assay and docking results revealed partial intercalation and DNA groove binding for the metal complexes. Overall, from the therapeutic point of view, ppy containing platinum complex (C1) is a favored anticancer agent, because it induces signaling cell death (apoptosis) in cancer cells, and lacks the necrotic effect.

Anticancer activity and DNA-binding properties of novel cationic Pt(II) complexes.

In this study, three structurally related cationic Pt complexes, [Pt(ppy)(dppe)]CF3CO2: C1, [Pt(bhq)(dppe)]CF3CO2: C2, and [Pt(bhq)(dppf)]CF3CO2: C3, in which ppy=deprotonated 2-phenylpyridine, bhq=deprotonated benzo[h]quinoline, dppe=bis(diphenylphosphino)ethane and dppf=1,1'-bis(diphenylphosphino)ferrocene, were used for the assessment of their anticancer activities against Jurkat and MCF-7 cancer cell lines. The Pt complexes (C1-C3) demonstrated significant level of anticancer properties, as measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Moreover, the changes in nuclear morphology with Acridine Orange (AO) staining reveal that these complexes are capable to induce apoptosis, and only C1 stimulates activity of Caspase-3 in Jurkat cancer cells. To get a better insight into the nature of binding between these cationic Pt complexes and DNA, different spectroscopic techniques and gel electrophoresis were applied. On the basis of the results of UV/vis absorption spectroscopy, CD experiment and fluorescence quenching of ethidium bromide (EB)-DNA, the interaction between DNA and the Pt complexes is likely to occur through a mixed-binding mode. Overall, the present work suggests that a controlled modification could result in new potentially antitumor complexes which can survive the repair mechanism and induce facile apoptosis.

Anticancer and DNA binding activities of platinum (IV) complexes; importance of leaving group departure rate.

The two six-coordinate Pt(IV) complexes, containing bidentate nitrogen donor/methyl ligands with general formula [Pt(X)2Me2((t)bu2bpy)], where (t)bu2bpy = 4,4'-ditert-butyl-2,2'-bipyridine and X = Cl (C1) or Br (C2), serving as the leaving groups were synthesized for evaluation of their anticancer activities and DNA binding properties. To examine anticancer activities of the synthetic complexes, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ethidium bromide/acridine orange (EB/AO) staining method were performed. The binding properties of these complexes to DNA and purine nucleotides were examined, using different spectroscopic techniques. These complexes demonstrated significant anticancer activities against three cancer cell lines Jurkat, K562, and MCF-7. On the basis of the results of EB/AO staining, C1 and C2 were also capable to induce apoptosis in cancer cells. These complexes comprise halide leaving groups, displaying different departure rates; accordingly, they demonstrated slightly dissimilar anticancer activity and significantly different DNA/purine nucleotide binding properties. The results of DNA interaction studies of these complexes suggest a mixed-binding mode, comprising partial intercalation and groove binding. Overall, the results presented herein indicate that the newly synthesized Pt(IV) complexes are promising class of the potential anticancer agents which can be considered as molecular templates in designing novel platinum anticancer drugs. This study also highlights the importance of leaving group in anticancer activity and DNA binding properties of Pt(IV) complexes.

Selectivity in metal-carbon bond protonolysis in p-tolyl- (or methyl)-cycloplatinated(II) complexes: kinetics and mechanism of the uncatalyzed isomerization of the resulting Pt(II) products.

Reaction of each of the known starting complexes [PtR(C^N)(SMe2)], 1, in which R = Me or p-MeC6H4 and C^N is either ppy (deprotonated 2-phenylpyridine) or bhq (deprotonated benzo[h]quinoline), with one equivalent of CF3CO2H, gave the complexes [Pt(C^N)(CF3CO2)(SMe2)], 3 (C^N = ppy, 3a; bhq, 3b). The bis-chelate complexes [Pt(C^N)(P^P)](CF3CO2), 4, were obtained by reaction of complexes 3 with one equivalent of either of the P^P bisphosphine reagents, dppf = 1,1'-bis(diphenylphosphino)ferrocene or dppe = bis(diphenylphosphino)ethane. Complexes 4 were alternatively made by reaction of the complexes [PtMe(κ(1)C-C^N)(P^P)], 2, with one equivalent of CF3CO2H. When the complex 3b was reacted with 0.5 equivalents of dppe, 0.5 equivalents of the related bis-chelate product, 4d, formed along with 0.5 equivalents of the unreacted starting complex 3b. In contrast, when the complex 3b was reacted with 0.5 equivalents of dppf, then the dimeric complex [Pt2(bhq)2(CF3CO2)2(µ-dppf)], 5, formed in pure form. In all the above-mentioned acid reactions, the M-R bond rather than the M-C bond of the cycloplatinated complex is cleaved. When the PPh3 analogues of complexes 1, i.e. the complexes [PtR(C^N)(PPh3)], 6, in which C^N is ppy or tpy = deprotonated 2-p-tolylpyridine, were reacted with one equivalent of CF3CO2H, the course of the reaction reversed and the M-C bonds of the cycloplatinated complexes are cleaved rather than the M-R bonds. The latter reaction gave [PtR(κ(1)N-HC^N)(PPh3)(CF3CO2)], as an equilibrium mixture of two isomers 7 and 8. Crystal structures of the typical complexes show a variety of extensive intermolecular hydrogen bonding involving C-H bonds from the different ligands and electronegative atoms (O or F) from the CF3CO2 moiety. On the basis of data obtained from kinetic studies (using (1)H NMR spectroscopy), a dissociative mechanism is proposed for the case of the 7c/8c isomerization process, involving dissociation of the κ(1)N-Htpy neutral ligand, rather than the alternative route of PPh3 or CF3CO2 ligand dissociation.

Thin film formation of platinum nanoparticles at oil-water interface, using organoplatinum(II) complexes, suitable for electro-oxidation of methanol.

A simple and effective strategy is presented to integrate individual platinum nanoparticles (NPs) into macroscopic thin films based on the reduction of organoplatinum(II) complexes [PtCl2(cod)] 1a, [PtI2(cod)] 1b (cod = 1,5-cyclooctadiene) and cis-[Pt(p-MeC6H4)2(SMe2)2] 2, at the toluene-water interface in the absence of stabilizer. Structure and morphology of the platinum NPs were characterized with X-ray diffraction (XRD), transmission electron microscopy (TEM), and selected area electron diffraction (SAED) techniques. Finally, platinum thin films were deposited on glassy carbon electrode and their electro-oxidation was investigated in the methanol oxidation reaction. Pt NPs thin films showed highly improved electrocatalytical activity toward methanol oxidation as compared with commercial platinum catalysts. The present method provides a facile and low-cost strategy toward the synthesis of different electrocatalysts of noble metals for application in fuel cells.

The anticancer activity and HSA binding properties of the structurally related platinum (II) complexes.

The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino) methane (Ph(2)PCH(2)PPh(2)) and dppa = bis(diphenylphosphino)amine (Ph(2)PNHPPh(2)), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF(6): C(1), [Pt(C^N)(dppa)]PF(6): C(2), and [Pt(C^N)I(dppa)]: C(3), toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure-activity relationship studies reveal that four-coordinated Pt complexes C(1) and C(2) with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated C(3) complex with the unusual intermolecular NH…Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest C(1) and C(2) as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins.

Multiple hydrogen bondings in a platinum complex.

An unprecedented example of a platinum(II) complex with simultaneous formation of intermolecular NH···I-Pt and CH···I-Pt H-bondings (with neighboring platinum center) and an intramolecular CH···Pt hydrogen bonding in solid state is described. There are indications showing that the complex in solution probably forms a different kind of H-bonding type interaction.

In vitro and in vivo antitumor activities and DNA binding mode of five coordinated cyclometalated organoplatinum(II) complexes containing biphosphine ligands.

New complexes [Pt(C(∧)N)Cl(dppa)] (1), and [Pt(C(∧)N)Cl(dppm)] (2), (C(∧)N. deprotonated 2-phenylpyridine; dppa. bis(diphenylphosphino)amine; dppm. bis(diphenylphosphino)methane) were suggested to have pentacoordinated geometry as investigated by NMR and conductometry. Pharmacological effects of 1 and 2 were evaluated for their proteasome-inhibitory and apoptosis-inducing activities under in vitro and in vivo conditions, showing significant proteasome-inhibitory activity against purified 20S proteasome, while 2 demonstrated superior inhibitory activity against cellular 26S proteasome. Consistently, this effect was associated with higher levels of proteasome target proteins and apoptosis induction in breast cancer cells. Importantly, preliminary studies show 1 and 2 were able to exert a similar effect in vivo by inhibiting the growth of breast cancer xenografts in mice, which was associated with proteasome inhibition and apoptosis induction. Interaction of 1 and 2 with herring sperm DNA was investigated by fluorimeteric emission, suggesting that Pt(II)-containing biphosphine complexes with DNA binding capabilities can also target and inhibit the tumor proteasome.

Oxidative addition reaction of diarylplatinum(II) complexes with MeI in ionic liquid media: a kinetic study.

A kinetic study of the oxidative addition reaction of diarylplatinum(II) complexes [Pt(p-MeC(6)H(4))(2)(NN)] (1a: NN = 1,10-phenanthroline (phen) and 1b: NN = 4,4'-di-tert-butyl-2,2'-bipyridine ((t)Bu(2)bpy)) with MeI in ionic liquids 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide ([bmim][bta]) or 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF(4)]) is described. The reactions were investigated as a function of MeI concentration and temperature under pseudo-first-order conditions using UV-vis spectroscopy techniques. In general, the oxidative addition reactions in ionic liquids followed an S(N)2 mechanism, similar to that reported for the related reactions in conventional solvents, e.g. benzene or acetone. The reaction rates in different solvents followed the order acetone > ionic liquids > benzene. The trend in the values of k(2) clearly indicated that ionic liquids behave like conventional solvents and that no particular 'ionic liquid effect' was detected in this kind of reaction. The effect of solvent on the reactions was examined using a linear solvation energy relationship (LSER) based on the Kamlet-Taft solvent scale. The activation parameters, DeltaH(++) and DeltaS(++), were obtained for the reactions in each solvent and the investigation of enthalpy-entropy compensation confirmed that the mechanism operated in all solvents is similar.

Cyclometalated organoplatinum(II) complexes: first example of a monodentate benzo[h]quinolyl ligand and a complex with bridging bis(diphenylphosphino)ethane.

The cyclometalated complexes [Pt(ppy)R(SMe(2))] or [Pt(bhq)R(SMe(2))], where ppyH = 2-phenylpyridine, bhqH = benzo[h]quinoline and R = methyl or p-tolyl, react with bis(diphenylphosphino)ethane, dppe, in a 1:1 ratio to give the corresponding complexes [Pt(κ(1)-C-ppy)R(dppe)] or [Pt(κ(1)-C-bhq)R(dppe)], in which the ppy or bhq ligands are monodentate and dppe is chelating. The similar reaction in a 2:1 ratio gives the binuclear complexes [{Pt(ppy)R}(2)(µ-dppe)] or [{Pt(bhq)R}(2)(µ-dppe)], in which the dppe ligands are in the unusual bridging bidentate bonding mode.