Synthesis, Structure and Biological Evaluations of Zn(II) Pincer Complexes Based on S-Triazine Type Chelator.

2,4-bis (3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (BPMT) pincer ligand was used to synthesize the new [Zn(BPMT)(NCS)2] (1) and [Zn(BPMT)(Br)2] (2) complexes by a reaction with Zn(NO3)2·6H2O in the presence of either KSCN or KBr, respectively. The structure of complex 1 has been exclusively confirmed using single crystal X-ray diffraction. In this neutral heteroleptic complex, the BPMT is a pincer chelate coordinating the Zn(II) ion via three interactions with the two pyrazole moieties and the s-triazine core. Hence, BPMT is a tridentate NNN-chelate. The coordination environment of Zn(II) is completed by two strong interactions with two terminal SCN- ions via the N-atom. Hence, the Zn(II) is penta-coordinated with a distorted square pyramidal coordination geometry. Hirshfeld analysis indicated the predominance of H…H, H…C and N…H intermolecular interactions. Additionally, the S…H, S…C and S…N contacts are the most significant. The free ligand has no or weak antimicrobial, antioxidant and anticancer activities while the studied Zn(II) complexes showed interesting biological activity. Complex 1 has excellent antibacterial activity against B. subtilis (2.4 µg/mL) and P. vulgaris (4.8 µg/mL) compared to Gentamycin (4.8 µg/mL). Additionally, complex 1 (78.09 ± 4.23 µg/mL) has better antioxidant activity than 2 (365.60 ± 20.89 µg/mL). In addition, complex 1 (43.86 ± 3.12 µg/mL) and 2 (30.23 ± 1.26 µg/mL) have 8 and 12 times the anticancer activity of the free BPMT ligand (372.79 ± 13.64 µg/mL).

Ultra-small bimetallic phosphides for dual-modal MRI imaging guided photothermal ablation of tumors.

Metal phosphides have been proved to be potential theranostic agents of tumors. However, the limitations of single-modal imaging or the treatment effect of such materials need to be further improved. Here, we successfully prepared polyvinylpyrrolidone-modified bimetallic nickel cobalt phosphide (NiCoP/PVP) nanoparticles as a theranostic agent of tumors. Owing to the different types of magnetic properties of Ni and Co components, T1- and T2-weighted magnetic resonance imaging (MRI) could be simultaneously achieved to compensate the low accuracy brought about by single-modal MRI. In addition, NiCoP/PVP possesses excellent photothermal properties owing to its obvious absorption in the near-infrared (NIR) region, which endows NiCoP/PVP with high photothermal conversion efficiency (PCE) to serve as a photothermal agent for tumor ablation. Therefore, NiCoP/PVP is a promising theranostic agent for accurate diagnosis and effective treatment of tumors.

Effect of cysteine thiols on the catalytic and anticancer activity of Ru(II) sulfonyl-ethylenediamine complexes.

We have synthesized a series of novel substituted sulfonyl ethylenediamine (en) RuII arene complexes 1-8 of [(η6-arene)Ru(R1-SO2-EnBz)X], where the arene is benzene, HO(CH2)2O-phenyl or biphenyl (biph), X = Cl or I, and R1 is phenyl, 4-Me-phenyl, 4-NO2-phenyl or dansyl. The 'piano-stool' structure of complex 3, [(η6-biph)Ru(4-Me-phenyl-SO2-EnBz)I], was confirmed by X-ray crystallography. The values of their aqua adducts were determined to be high (9.1 to 9.7). Complexes 1-8 have antiproliferative activity against human A2780 ovarian, and A549 lung cancer cells with IC50 values ranging from 4.1 to >50 µM, although, remarkably, complex 7 [(η6-biph)Ru(phenyl-SO2-EnBz)Cl] was inactive towards A2780 cells, but as potent as the clinical drug cisplatin towards A549 cells. All these complexes also showed catalytic activity in transfer hydrogenation (TH) of NAD+ to NADH with sodium formate as hydride donor, with TOFs in the range of 2.5-9.7 h-1. The complexes reacted rapidly with the thiols glutathione (GSH) and N-acetyl-L-cysteine (NAC), forming dinuclear bridged complexes [(η6-biph)2Ru2(GS)3]2- or [(η6-biph)2Ru2(NAC-H)3]2-, with the liberation of the diamine ligand which was detected by LC-MS. In addition, the switching on of fluorescence for complex 8 in aqueous solution confirmed release of the chelated DsEnBz ligand in reactions with these thiols. Reactions with GSH hampered the catalytic TH of NAD+ to NADH due to the decomposition of the complexes. Co-administration to cells of complex 2 [(η6-biph)Ru(4-Me-phenyl-SO2-EnBz)Cl] with L-buthionine sulfoximine (L-BSO), an inhibitor of GSH synthesis, partially restored the anticancer activity towards A2780 ovarian cancer cells. Complex 2 caused a concentration-dependent G1 phase cell cycle arrest, and induced a significant level of reactive oxygen species (ROS) in A2780 human ovarian cancer cells. The amount of induced ROS decreased with increase in GSH concentration, perhaps due to the formation of the dinuclear Ru-SG complex.

Quaternary Selenides EuLnCuSe3: Synthesis, Structures, Properties and In Silico Studies.

In this work, we report on the synthesis, in-depth crystal structure studies as well as optical and magnetic properties of newly synthesized heterometallic quaternary selenides of the Eu+2Ln+3Cu+1Se3 composition. Crystal structures of the obtained compounds were refined by the derivative difference minimization (DDM) method from the powder X-ray diffraction data. The structures are found to belong to orthorhombic space groups Pnma (structure type Ba2MnS3 for EuLaCuSe3 and structure type Eu2CuS3 for EuLnCuSe3, where Ln = Sm, Gd, Tb, Dy, Ho and Y) and Cmcm (structure type KZrCuS3 for EuLnCuSe3, where Ln = Tm, Yb and Lu). Space groups Pnma and Cmcm were delimited based on the tolerance factor t', and vibrational spectroscopy additionally confirmed the formation of three structural types. With a decrease in the ionic radius of Ln3+ in the reported structures, the distortion of the (LnCuSe3) layers decreases, and a gradual formation of the more symmetric structure occurs in the sequence Ba2MnS3 → Eu2CuS3 → KZrCuS3. According to magnetic studies, compounds EuLnCuSe3 (Ln = Tb, Dy, Ho and Tm) each exhibit ferrimagnetic properties with transition temperatures ranging from 4.7 to 6.3 K. A negative magnetization effect is observed for compound EuHoCuSe3 at temperatures below 4.8 K. The magnetic properties of the discussed selenides and isostructural sulfides were compared. The direct optical band gaps for EuLnCuSe3, subtracted from the corresponding diffuse reflectance spectra, were found to be 1.87-2.09 eV. Deviation between experimental and calculated band gaps is ascribed to lower d states of Eu2+ in the crystal field of EuLnCuSe3, while anomalous narrowing of the band gap of EuYbCuSe3 is explained by the low-lying charge-transfer state. Ab initio calculations of the crystal structures, elastic properties and phonon spectra of the reported compounds were performed.

Synthesis and formulation of [64Cu]Cu-PTSM for PET perfusion imaging in small animal models.

PURPOSE: The [64Cu]Cu-PTSM radiopharmaceutical, pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II), is suitable for use in microPET and autoradiographic imaging to assess regional tissue perfusion in small animal models. We report here an approach to synthesis and formulation of the [64Cu]Cu-PTSM radiopharmaceutical at the high concentrations required for use in imaging with rodent models of human disease. METHODS: The [64Cu]Cu-PTSM radiopharmaceutical was prepared at small volumes by addition of the H2PTSM ligand to acetate-buffered [64Cu]copper chloride, followed by solid phase extraction to isolate and purify the product, which was then recovered and formulated in 2-mL normal saline containing 5% ethanol and 5% propylene glycol. RESULTS: The [64Cu]Cu-PTSM radiopharmaceutical has been produced over the range of 0.41-1.85 GBq (11-50 mCi) [64Cu]Cu-PTSM in the 2.0-mL final product volume. Radiochemical purity of the [64Cu]Cu-PTSM radiopharmaceutical product averaged 99.8 ± 0.4% (n = 64), with the final formulated product produced at an 83 ± 5% radiochemical yield. CONCLUSIONS: The approach to [64Cu]Cu-PTSM synthesis and formulation has proven to be reliable and robust, supporting radiopharmaceutical delivery at the high concentrations required for PET studies in mouse and other rodent models.

Development of methylated cobalt-alkyne complexes with selective cytotoxicity against COX-positive cancer cell lines.

Derivatives of the cytotoxic cyclooxygenase (COX) inhibitor [(prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS) with a methyl group in the 3, 4, 5, or 6 position of the acetylsalicylic acid (ASS) scaffold were synthesized with the aim to achieve enhanced selectivity for COX-2. From this modification, a higher specificity for COX-2-expressing tumors is expected, preventing COX-1-mediated side effects. The cobalt-alkyne complexes were tested for their COX-inhibitory and antiproliferative properties as well as their cellular uptake. Methylation reduced the effects at the isolated COX-1, whereas those at the isolated COX-2 remained nearly constant compared to Co-ASS. In cellular systems, the new compounds showed superior cytotoxicity toward the COX-positive HT-29 colon carcinoma cells than cisplatin. The reduced growth-inhibitory potency in T-24 cells, which express distinctly fewer COX enzymes (COX-1/COX-2 = 50/1) than HT-29 cells (COX-1/COX-2 = 50/50), and the only marginal activity in COX-negative MCF-7 breast cancer cells point to an interference in the arachidonic acid cascade through COX-2 inhibition as part of the mode of action, especially as the cellular uptake was even higher in MCF-7 cells than in T-24 cells. These findings clearly demonstrate that the methylated cobalt-alkyne complexes possess promising potential for further development as reasonable alternatives to the limited platinum-based antitumor agents.

Improved Photodynamic Activity of Phthalocyanine by Adjusting the Chirality of Modified Amino Acids.

Herein, four zinc phthalocyanines (ZnPcs) with chiral lysine modification were synthesized. We found that the chirality of lysine and the chiral structure position strongly influence the properties of ZnPcs. Among the four ZnPcs, d-lysine-modified ZnPc through -NH2 on Cε [denoted N(ε)-d-lys-ZnPc] showed superior properties, including tumor enrichment, cancer cell uptake, and tumor retention capability, compared to the other three ZnPcs. Thus, chiral molecule modification is a simple and effective strategy to regulate the abovementioned properties to achieve a satisfactory antitumor outcome of drugs.

Synthesis and Evaluation of Antioxidant, Anti-Edematogenic and Antinociceptive Properties of Selenium-Sulfa Compounds.

Herein we describe results for the synthesis and synthetic application of 4-amino-3-(arylselenyl)benzenesulfonamides, and preliminary evaluation of antioxidant, anti-edematogenic and antinociceptive properties. This class of compounds was synthesized in good yields by a reaction of commercially available sulfanilamide and diorganyl diselenides in the presence of 10 mol% of I2 . Furthermore, the synthesized compound 4-amino-3-(phenylselenyl)benzenesulfonamide (3 a) was evaluated on complete Freund's adjuvant (CFA)-induced acute inflammatory pain. Dose- and time-response curves of antinociceptive effect of compound 3 a were performed using this experimental model. Also, the effect of compound 3 a was monitored in a hot-plate test to evaluate the acute non-inflammatory antinociception. The open-field test was performed to evaluate the locomotor and exploratory behaviors of mice. Oxidative stress markers, such as glutathione peroxidase activity; reactive species, non-protein thiols, and lipid peroxidation levels were performed to investigate the antioxidant action of compound 3 a. Our findings suggest that the antioxidant effect of compound 3 a may contribute to reducing the nociception and suppress the signaling pathways of inflammation on the local injury induced by CFA. Thus, compound 3 a reduced the paw edema as well as the hyperalgesic behavior in mice, being a promising therapeutic agent for the treatment of painful conditions.

A General, Multimetallic Cross-Ullmann Biheteroaryl Synthesis from Heteroaryl Halides and Heteroaryl Triflates.

Despite their importance to medicine and materials science, the synthesis of biheteroaryls by cross-coupling remains challenging. We describe here a new, general approach to biheteroaryls: the Ni- and Pd-catalyzed multimetallic cross-Ullmann coupling of heteroaryl halides with triflates. An array of 5-membered, 6-membered, and fused heteroaryl bromides and chlorides, as well as aryl triflates derived from heterocyclic phenols, proved to be viable substrates in this reaction (62 examples, 63 ± 17% average yield). The generality of this approach to biheteroaryls was further demonstrated in 96-well plate format at 10 µmol scale. An array of 96 possible products provided >90% hit rate under a single set of conditions. Further, low-yielding combinations could be rapidly optimized with a single "Toolbox Plate" of ligands, additives, and reductants.

In Situ Functionalization of Cellulose with Zinc Pyrithione for Antimicrobial Applications.

Considering the public health demands for stronger and effective personal protective clothing, herein, antimicrobial fabrics using a known bacteriostatic and fungistatic drug zinc pyrithione (ZPT) have been reported. ZPT was synthesized in situ on cellulosic fabric, viscose (VC), using a zinc metal precursor and 2-mercaptopyridine-N-oxide as a ligand (VC-ZPT). For comparison, viscose was also phosphorylated (VP) before in situ functionalization with ZPT (VP-ZPT). Both approaches provided adequate protection from microbes; however, functionalization of cellulose with phosphate (VP) resulted in the formation of a linking group between cellulose and ZPT, which exhibited better uniformity of ZPT over the fabric surface and higher durability to washing. The functionalization was confirmed by inductively coupled plasma mass spectroscopy (ICP-MS), scanning electron microscopy (SEM), and Raman spectroscopy. Further, the bonding of phosphate with ZPT was confirmed by 31P solid-state NMR. The physical properties, such as appearance, bending length, and mechanical strength, of the treated fabrics remained unchanged. The antimicrobial activities of VP-ZPT with VC-ZPT were studied against Escherichia coli, Staphylococcus aureus, and Candida albicans, which were found to be effective until 20 laundry cycles in VP-ZPT. Additionally, VP-ZPT samples exhibited poor adherence of bacteria on the fabric surface. The functionalized fabrics may find applications for topical skin diseases in reducing the necessity of repeated use of antibiotic ointments.

Intramolecular Hydrogen-Bond Interactions Tune Reactivity in Biomimetic Bis(µ-hydroxo)dicobalt Complexes.

Active site hydrogen-bond (H-bond) networks represent a key component by which metalloenzymes control the formation and deployment of high-valent transition metal-oxo intermediates. We report a series of dinuclear cobalt complexes that serve as structural models for the nonheme diiron enzyme family and feature a Co2(µ-OH)2 diamond core stabilized by intramolecular H-bond interactions. We define the conditions required for the kinetically controlled synthesis of these complexes: [Co2(µ-OH)2(µ-OAc)(κ1-OAc)2(pyR)4][PF6] (1R), where OAc = acetate and pyR = pyridine with para-substituent R, and we describe a homologous series of 1R in which the para-R substituent on pyridine is modulated. The solid state X-ray diffraction (XRD) structures of 1R are similar across the series, but in solution, their 1H NMR spectra reveal a linear free energy relationship (LFER) where, as R becomes increasingly electron-withdrawing, the intramolecular H-bond interaction between bridging µ-OH and κ1-acetate ligands results in increasingly "oxo-like" µ-OH bridges. Deprotonation of the bridging µ-OH results in the quantitative conversion to corresponding cubane complexes: [Co4(µ-O)4(µ3-OAc)4(pyR)4] (2R), which represent the thermodynamic sink of self-assembly. These reactions are unusually slow for rate-limiting deprotonation events, but rapid-mixing experiments reveal a 6000-fold rate acceleration on going from R = OMe to R = CN. These results suggest that we can tune reactivity by modulating the µ-OH pKa in the presence of intramolecular H-bond interactions to maintain stability as the octahedral d6 centers become increasingly acidic. Nature may similarly employ dynamic carboxylate-mediated H-bond interactions to control the reactivity of acidic transition metal-oxo intermediates.

Fractal-Percolation Structure Architectonics in Sol-Gel Synthesis.

It was developed a new technique to assess micro- and mesopores with sizes below a few nanometers. The porous materials with hierarchical fractal-percolation structure were obtained with the sol-gel method. The tetraethoxysilane hydrolysis and polycondensation reactions were performed in the presence of salts as the sources of metal oxides. The porous materials were obtained under spinodal decomposition conditions during application of the polymer sol to the substrate surface and thermal treatment of the structures. The model is based on an enhanced Kepler net of the 4612 type with hexagonal cells filled with a quasi-two-dimensional projection of the Jullien fractal after the 2nd iteration. The materials obtained with the sol-gel method were studied using the atomic force microscopy, electron microscopy, thermal desorption, as well as an AutoCAD 2022 computer simulation of the percolation transition in a two-component system using the proposed multimodal model. Based on the results obtained, a new method was suggested to assess micro- and mesopores with sizes below a few nanometrs, which cannot be analyzed using the atomic force microscopy and electron microscopy.

Mechanistic Investigation of the Iron-Catalyzed Azidation of Alkyl C(sp3)-H Bonds with Zhdankin's λ3-Azidoiodane.

An in-depth study of the mechanism of the azidation of C(sp3)-H bonds with Zhdankin's λ3-azidoiodane reagent catalyzed by iron(II)(pybox) complexes is reported. Previously, it was shown that tertiary and benzylic C(sp3)-H bonds of a range of complex molecules underwent highly site-selective azidation by reaction with a λ3-azidoiodane reagent and an iron(II)(pybox) catalyst under mild conditions. However, the mechanism of this reaction was unclear. Here, a series of mechanistic experiments are presented that reveal critical features responsible for the high selectivity and broad scope of this reaction. These experiments demonstrate the ability of the λ3-azidoiodane reagent to undergo I-N bond homolysis under mild conditions to form λ2-iodanyl and azidyl radicals that undergo highly site-selective and rate-limiting abstraction of a hydrogen atom from the substrate. The resultant alkyl radical then combines rapidly with a resting state iron(III)-azide complex, which is generated by the reaction of the λ3-azidoiodane with the iron(II)(pybox) complex, to form the C(sp3)-N3 bond. This mechanism is supported by the independent synthesis of well-defined iron complexes characterized by cyclic voltammetry, X-ray diffraction, and EPR spectroscopy, and by the reaction of the iron complexes with alkanes and the λ3-azidoiodane. Reaction monitoring and kinetic studies further reveal an unusual effect of the catalyst on the rate of formation of product and consumption of reactants and suggest a blueprint for the development of new processes leading to late-stage functionalization of C(sp3)-H bonds.

Synthesis and biological evaluation of zwitterionic half-sandwich Rhodium(III) and Ruthenium(II) organometallic complexes.

Herein we present the synthesis and characterization of a panel of structurally related zwitterionic piano-stool rhodium(III) and ruthenium(II) complexes. The identities of these novel complexes have been determined by NMR spectroscopy, mass spectrometry, elemental analysis and single-crystal X-ray crystallography. The stability and fluorescence property of these zwitterionic complexes were also confirmed. Zwitterionic rhodium(III) complexes Rh1-Rh4 displayed potent cytotoxic activity against A549 and HeLa human cancer cells. On the contrary, zwitterionic ruthenium(II) complexes Ru1-Ru4 presented no obvious cytotoxic activity to the test cell lines. Moreover, the trend that the introduction of fluorinated substituent and phenyl ring in the η5-CpR ring and N,N-chelating ligand, respectively, could enhance the cytotoxicity of these zwitterionic rhodium(III) complexes, were observed. The exploration of mechanism using flow cytometry displayed that the cytotoxicity of these rhodium(III) complexes was associated with the perturbation of the cell cycle and the induction of cell apoptosis. Furthermore, microscopic analysis using confocal microscopy indicated that the representative rhodium(III) complex Rh4 entered A549 cells via energy-dependent pathway and predominantly accumulated in lysosomes, thus leading to the disruption of lysosomal integrity.

New titanocene derivative with improved stability and binding ability to albumin exhibits high anticancer activity.

Titanium-based therapies have emerged as a promising alternative for the treatment of cancer patients, particularly those with cisplatin resistant tumors. Unfortunately, some titanium compounds show stability and solubility problems that have hindered their use in clinical practice. Here, we designed and synthesized a new titanium complex containing a titanocene fragment, a tridentate ligand to improve its stability in water, and a long aliphatic chain, designed to facilitate a non-covalent interaction with albumin, the most abundant protein in human serum. The stability and human serum albumin affinity of the resulting titanium complex was investigated by UV-Vis absorption and fluorescence spectroscopy techniques. Complex [TiCp2{(OOC)2py-O-myr}] (3) (myr = C14H29, py = pyridine) and its analogous [TiCp2{(OOC)2py-OH}] (4), lacking the aliphatic chain, showed improved stability in phosphate saline buffer compared with [TiCp2Cl2] (1). 3 showed a strong interaction with human serum albumin in a 1:1 stoichiometry. The cytotoxic effect of 3 was higher compared to [TiCp2Cl2] in tumor cell lines and showed potential tumor selectivity when assayed in non-tumor human epithelial cells. Finally, 3 showed an antiproliferative effect on cancer cells, decreasing the population in the S phase, and increasing apoptotic cells in a significant manner. All this makes the novel Ti(IV) compound 3 a firm candidate to continue further studies of its therapeutic potential in vitro and in vivo.

Development of a protein assay with copper chelator chromeazurol B, based on the biuret reaction.

This study aimed to provide a novel and highly sensitive protein assay based on the biuret reaction and using chromeazurol B, a metal chelate compound. The method consists of two reagents and an automated analyzer. First, a complex of copper and protein (biuret reaction) is formed. Second, a chelating reagent containing chromeazurol B forms a three-dimensional complex of protein, copper, and chromeazurol B at neutral pH, resulting in highly sensitive coloration. The intra-assay (n = 20) variation for the three levels was 3.54 % or lower at each concentration. Each response with α, ß-, and γ-globulin was 103.8 % and 104.3 %, respectively, against albumin. The molar absorption coefficient (ε) of the present method was 2.5 × 105 m2/mol against human albumin, higher than that of the commercially available Lowry method (ε = 8.7 × 104 m2/mol), which is based on the same principle. The correlation test for the pyrogallol method with 30 urine samples showed good performance (r = 0.961). The method described here (the Biuret-based CAB method) is a more sensitive and rapid assay than the Lowry method, and it may also be applied to biological samples because of its similar reactivity towards various proteins.

Enantiomerically Enriched α-Borylzinc Reagents by Nickel-Catalyzed Carbozincation of Vinylboronic Esters.

In this paper is described a synthesis of enantiomerically enriched, configurationally stable organozinc reagents by catalytic enantioselective carbozincation of a vinylboronic ester. This process furnishes enantiomerically enriched α-borylzinc intermediates that are shown to undergo stereospecific reactions, producing enantioenriched secondary boronic ester products. The properties of the intermediate α-borylzinc reagent are probed and the synthetic utility of the products is demonstrated by application to the synthesis of (-)-aphanorphine and (-)-enterolactone.

The Composites of PCL and Tetranuclear Titanium(IV)-oxo Complexes as Materials Exhibiting the Photocatalytic and the Antimicrobial Activity.

Excessive misuse of antibiotics and antimicrobials has led to a spread of microorganisms resistant to most currently used agents. The resulting global threats has driven the search for new materials with optimal antimicrobial activity and their application in various areas of our lives. In our research, we focused on the formation of composite materials produced by the dispersion of titanium(IV)-oxo complexes (TOCs) in poly(ε-caprolactone) (PCL) matrix, which exhibit optimal antimicrobial activity. TOCs, of the general formula [Ti4O2(OiBu)10(O2CR')2] (R' = PhNH2 (1), C13H9 (2)) were synthesized as a result of the direct reaction of titanium(IV) isobutoxide and 4-aminobenzoic acid or 9-fluorenecarboxylic acid. The microcrystalline powders of (1) and (2), whose structures were confirmed by infrared (IR) and Raman spectroscopy, were dispersed in PCL matrixes. In this way, the composites PCL + nTOCs (n = 5 and 20 wt.%) were produced. The structure and physicochemical properties were determined on the basis of Raman microscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), electron paramagnetic resonance spectroscopy (EPR), and UV-Vis diffuse reflectance spectroscopy (DRS). The degree of TOCs distribution in the polymer matrix was monitored by scanning electron microscopy (SEM). The addition of TOCs micro grains into the PCL matrix only slightly changed the thermal and mechanical properties of the composite compared to the pure PCL. Among the investigated PCL + TOCs systems, promising antibacterial properties were confirmed for samples of PCL + n(2) (n = 5, 20 wt.%) composites, which simultaneously revealed the best photocatalytic activity in the visible range.

Naphthalene-facilitated self-assembly of a Gd-chelate as a novel T2 MRI contrast agent for visualization of stem cell transplants.

Naphthalene is coupled with DOTA via a peptide sequence to yield an amphipathic MRI probe Nap-CFGKTG-DOTA-Gd (Nap-Gd) that can self-assemble into nanofibers. Incubation of NSCs, hMSCs and L929 cells in the presence of Nap-Gd in the µM level can introduce a significant amount of Nap-Gd into the cells as nanoclusters or nanofibers. The resultant intracellular Gd content is 10-60 times that achieved by incubation with Dotarem at the same concentration. The labelled cells exhibit a significant hyperintensive effect under T1-weighted MRI and a significant hypointensive effect under T2-weighted MRI. The hypointensive effect is more persistent than the hyperintensive effect, which allows in vivo tracking of labelled hMSCs for over 12 days under T2-weighted MRI. A comprehensive interpretation of the MRI signal intensity and the associated relaxation times reveals the structure-function relationship between the binding status of Nap-Gd in cells (structure) and the magnetic relaxation processes (function) toward a full understanding of the observed hyperintensive and hypointensive effects.

Organometallic dendrimers based on Ruthenium(II) N-heterocyclic carbenes and their implication as delivery systems of anticancer small interfering RNA.

With the purpose of obtaining a new dendritic system against cancer, this paper is focused on the synthesis of spherical carbosilane metallodendrimers of different generations holding Ru(II) N-heterocyclic carbene (NHC) on the periphery from the imidazolium precursors. Both imidazolium salt dendrimers and their metallodendrimers counterparts showed promising anticancer activity, similar to cisplatin, mainly at high generations. In addition, both families of second and third generations were able to form dendriplexes with anticancer small interfering RNA (siRNA), protecting the cargo against RNAse and being able to internalize it in HEPG2 (human liver cancer) tumour cells. The characterization and effectiveness of the dendriplexes were evaluated by various analytical techniques such as zeta potential, electrophoresis and circular dichroism, the stability of the system and the protective nature of the dendrimer estimated using RNAse and the internalization of dendriplexes by confocal microscopy. The major advantage observed with the ruthenium metallodendrimers with respect to the imidazolium salts precursors was in cellular uptake, where the internalization of Mcl-1-FITC siRNA (myeloid cell leukaemia-1 fluorescein labelled siRNA) proceeded more efficiently. Therefore, we propose here that both imidazolium and Ru metallodendrimers are interesting candidates in cancer due to their double action, as anticancer per se and as carrier for anticancer siRNA, providing in this way a combined action.