Complex C3 Research Articles

Novel half-sandwich ruthenium(II) nicotinic hydrazone complexes: An efficient class of catalyst for the N-alkylation of amines with benzyl alcohol via transfer hydrogen mechanism and effective antibacterial agents

A new series of half sandwich ruthenium(II) complexes supported by nicotinic acid hydrazone derivatives of general formula [Ru(ɳ6-p-cymene)(Cl)(L)], where L represents N’-benzylidenenicotinohydrazide (HL1), N’-(naphthalen-1-ylmethylene)nicotinohydrazide (HL2) or N’-(pyren-1-ylmethylene)nicotinohydrazide (HL3) were synthesized and fully characterized. The solid-state molecular structures of ligands and complexes were elucidated with single-crystal X-ray diffraction. The ligands HL1 and HL2 possess monoclinic crystal system with P21/c and C2/c space groups respectively, whereas all the three Ru(II) complexes C1–3 are typical three-legged piano-stool geometries with orthorhombic(Aba2) (C1) and triclinic(P-1) (C2–3) systems respectively. The catalytic activities of these ruthenium complexes in the synthesis of N-alkylated amines were explored. Under optimal reaction condition, the complex C3 was found to be the most efficient catalyst for the N-alkylation of primary to secondary amines using benzyl alcohol. A wide range of substrates have been studied that includes anilines bearing electron withdrawing/electron donating group, fused aromatic, heteroaromatic, alicyclic and aliphatic amines with good to excellent yield. In addition, the antibacterial activity of the complexes were tested against different human pathogenic bacteria, among them C2 complex with naphthyl moiety was found to be the most active one against both Gram-positive (S. aureus and E. faecalis) and Gram-negative (E. coli and K. pneumoniae) bacteria. These two different studies demonstrate the catalytic and biological importance of our newly prepared Ruthenium complex.

A combined theoretical and experimental approach to determine the right choice of co-ligand to impart spin crossover in Fe(II) complexes based on 1,3,4-oxadiazole ligands.

We present the synthesis of two new novel tetradentate ligands based on 1,3,4-oxadiazole, 2-(2-pyridyl)-5-[N,N-bis(2-pyridylmethyl)aminomethyl]-1,3,4-oxadiazole (LTetraPy-ODA) and 2-(2-phenyl)-5-[N,N-bis(2-pyridylmethyl)aminomethyl]-1,3,4-oxadiazole (LTetraPh-ODA). The ligands were used to prepare six mononuclear complexes [FeII(LTetraPy-ODA)(NCE)] (C1-C3) and [FeII(LTetraPh-ODA)(NCE)] (C4-C6) where E = S, Se or BH3. In addition, the ligand LTetraPy-ODA was employed in the synthesis of a new di-nuclear complex [FeII2(LTetraPh)](ClO4)4·1 CH3NO2·1.5 H2O (C7). Characterization of all complexes was carried out using single-crystal X-ray crystallography, elemental analysis, and infrared spectroscopy. Magnetic susceptibility measurements, performed in the temperature range of 2-300 K using a SQUID magnetometer, revealed spin crossover behaviour exclusively in the mononuclear complexes C3 and C6, in which two monodentate NCBH3- co-ligands coordinate. The presence of the lattice solvent was found to be crucial to the spin transition property, with complex C3 exhibiting a switching temperature (T1/2) of approximately 165 K and C6 approximately 194 K. The other four mononuclear complexes C1, C2, C4, C5, as well as the dinuclear complex C7 are locked in the high spin state over the measured temperature range. Density Functional Theory (DFT) calculations were performed on complexes C1-C6 to rationalise the observed magnetic behaviour, demonstrating the significant effect of the NCS-, NCSe- and NCBH3- co-ligands ligands on the spin-crossover behaviour of the [FeII(L)(NCE)] complexes.

Investigation of new ferrocenyl-artesunate derivatives as antiparasitics.

Artesunate (Ars) is a semisynthetic antimalarial drug and is a part of the artemisinin-based combination therapy arsenal employed for malaria treatment. The drug functions mainly by activation of its endoperoxide bridge leading to increased oxidative stress in malaria parasites. The purpose of this study was to ascertain the antiparasitic effects of combining ferrocene and Arsvia short or long chain ester or amide linkages (C1-C4). The compounds were evaluated for growth inhibition activity on the apicomplexan parasites, Plasmodium falciparum (P. falciparum) and Toxoplasma gondii (T. gondii). All the complexes demonstrated good activity against T. gondii with IC50 values in the low micromolar range (0.28-1.2 μM) and good to excellent antimalarial activity against a chloroquine sensitive strain of P. falciparum (NF54). Further investigations on T. gondii revealed that the likely mode of action (MoA) is through the generation of reactive oxygen species. Additionally, immunofluorescence microscopy suggested a novel change in the morphology of the parasite by complex C3, an artesunate-ferrocenyl ethyl amide complex. The complexes were not cytotoxic or showed low cytotoxicity to two normal cell lines tested.

Electro- and photochemical H2 generation by Co(ii) polypyridyl-based catalysts bearing ortho-substituted pyridines.

Cobalt(ii) complexes featuring hexadentate amino-pyridyl ligands have been recently discovered as highly active catalysts for the Hydrogen Evolution Reaction (HER), whose high performance arises from the possibility of assisting proton transfer processes via intramolecular routes involving detached pyridine units. With the aim of gaining insights into such catalytic routes, three new proton reduction catalysts based on amino-polypyridyl ligands are reported, focusing on substitution of the pyridine ortho-position. Specifically, a carboxylate (C2) and two hydroxyl substituted pyridyl moieties (C3, C4) are introduced with the aim of promoting intramolecular proton transfer which possibly enhances the efficiency of the catalysts. Foot-of-the-wave and catalytic Tafel plot analyses have been utilized to benchmark the catalytic performances under electrochemical conditions in acetonitrile using trifluoroacetic acid as the proton source. In this respect, the cobalt complex C3 turns out to be the fastest catalyst in the series, with a maximum turnover frequency (TOF) of 1.6 (±0.5) × 105 s-1, but at the expense of large overpotentials. Mechanistic investigations by means of Density Functional Theory (DFT) suggest a typical ECEC mechanism (i.e. a sequence of reduction - E - and protonation - C - events) for all the catalysts, as previously envisioned for the parent unsubstituted complex C1. Interestingly, in the case of complex C2, the catalytic route is triggered by initial protonation of the carboxylate group resulting in a less common (C)ECEC mechanism. The pivotal role of the hexadentate chelating ligand in providing internal proton relays to assist hydrogen elimination is further confirmed within this novel class of molecular catalysts, thus highlighting the relevance of a flexible polypyridine ligand in the design of efficient cobalt complexes for the HER. Photochemical studies in aqueous solution using [Ru(bpy)3]2+ (where bpy = 2,2'-bipyridine) as the sensitizer and ascorbate as the sacrificial electron donor support the superior performance of C3.

Heterodinuclear Ru-Pt Complexes Bridged with 2,3-Bis(pyridyl)pyrazinyl Ligands: Studies on Kinetics, Deoxyribonucleic Acid/Bovine Serum Albumin Binding and Cleavage, In Vitro Cytotoxicity, and In Vivo Toxicity on Zebrafish Embryo Activities.

Di- and poly-homo/heteronuclear complexes have great potential as anticancer drugs. Here, we report their reactivity, deoxyribonucleic acid (DNA)/bovine serum albumin (BSA) binding and cleavage interactions, in vitro cytotoxicity, and in vivo zebrafish embryo toxicity of [(phen)2Ru(μ-L)PtCl2]2+ (phen = 1,10-phenanthroline and L = 2,3-bis(2-pyridyl)pyrazine, bpp, C1; 2,3-bis(2-pyridyl)quinoxaline, bpq, C2ial; 2,3-bis(2-pyridyl)benzo[g]quinoxaline, bbq, C3) anticancer prodrugs. The substitution reactivity increases from C1 to C3 owing to an increase in the π-conjugation on the bridging chelate which facilitates π-back bonding. As a result, the electrophilicity index on the C3 complex increases than that on the complex C2 followed by C1 which leads to higher rates of substitution and thus the reactivity order follows C1 < C2 < C3. The coordination of Ru at one end of each of the complexes enhances water solubility. Moreover, the charge addition of the two metal ions increases their reactivity toward substitution in addition to ensuring electrostatic interactions at target sites such as the DNA/BSA. Spectroscopic (UV–vis absorption and fluorescence quenching) titration and viscosity measurement results of the interactions of C1/2/3 with CT-DNA established the formation of stable, nonconvent C1/2/3-DNA adducts with DNA most likely via the intercalative binding mode. Furthermore, studies with BSA showed a good binding affinity of these complexes owing to hydrophobic interactions with the coordinated ligands. The interactions of these complexes with DNA/BSA are in line with the reactivity trend, and all these experimental findings were further supported by molecular docking analysis. In vitro MTT cytotoxic activities on human breast cancer cell line MCF-7 revealed that all the complexes have high cytotoxicity activity (IC50 > 9 μM); furthermore, the selectivity index and SI values were higher (>3). Complex C3 showed the highest cytotoxicity with IC50 = 3.1 μM and SI value (5.55) against MCF7 cell lines and these values were comparable to those of the cisplatin (IC50 and SI values are 5.0 μM and 4.02, respectively). In vivo toxicological assessments on zebrafish embryos revealed that all the Ru–Pt complexes (CI/2/3) have poor embryo acute toxic effects over 96 h postfertilization, hpf with LC50 > 65.2 μM. The complex C3 has shown the lowest embryo toxicity (LC50 = 148.8 μM), which is comparable to that of commercial cisplatin (LC50 = 181.1 μM). Based on the cytotoxicity results, complexes C2 and C3 could be considered for further development as chemotherapeutic agents against MCF breast cancer cells.

Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes.

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η6-arene)Ru(N,N′)L][PF6]2 containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).

The six dimensions of SU (3)

The QCD theory uses eight generating GellMann matrices for its SU(3) symmetry presenting the strong interaction. Instead of attributing the basic six color charges in QCD only to gluons and quarks, they are treated as an independent energy cc which has its six values from the sequence of complex cross ratios. The space for them is a complex C³ with an energy plane added to spacetime. In octonian coordinates, two octonian dimensions are missing. Octonian models are presented where the color charges act independent of QCD. The catastrophe, models and field quantum used are the parabolic umbilic, the 6 roll mill, the hedgehog and rgb-gravitons, generating barycentrical coordinates where Higgs can set mass as weight at a barycenter. The conic color charge whirls rgb red-green-blue are in superposition the neutral color charge of all baryons and nucleons.

ONSN]-type chromium complexes catalyzed coupling of CO2 with epoxides

A new family of [ONSN]-type chromium complexes bearing hybrid coordination site (O, N, S) have been developed for the coupling of epoxides with CO2. The catalytic system resulting from the complex C2 in combination with TBAB shows the high activity for the cycloaddition of epoxides with CO2 with a broad range of substrates including terminal epoxides and internal epoxides. When catalytic system is switched from complex C2 and TBAB to complex C3 and PPNCl as well as regulation of the reaction conditions, which causes the variation of chemo-selectivity and allows the highly selective synthesis of poly(cyclohexene carbonate) by employing cyclohexene oxide as substrate. The spectroscopic analysis, including UV–vis, FT-IR, and ESIMS, pointed to the formation of new chromium complex, which may be an active species in the reaction.

Comminuted AO-C3 fractures of the patella: good outcome using anatomically contoured locking plate fixation.

The treatment of comminuted patellar fractures remains a challenge for orthopedic surgeons. The aim of this study was to assess the clinical, functional, and radiological outcome after treatment of comminuted patellar fractures using an anatomically contoured plating system. Between January 2015 and December 2019 (5years), 29 patients with complex C3 fractures according to AO classification (18 female, 11 male; mean age: 53years) were treated using an anatomically contoured plating system (patella SuturePlate™, Arthrex®, Naples, USA). Indication for surgery was based on instability and/or initial fragment dislocation (> 2mm). After a minimum follow-up of 12months, patients were examined using a standardized clinical examination and functional outcome was assessed using specific knee scores (Lysholm, WOMAC, IKDC, Kujala, and Tegner score). In addition, complications were recorded and all available radiographs were evaluated regarding osteoarthritis and reduction quality. All patients returned for follow-up investigation after an average of 19months (range: 12-48months). A mean range of motion (ROM) of 131° (range: 100-150) was recorded. Overall good functional outcome parameters could be reported, with a mean Lysholm score of 84.7 (range: 100-45), a WOMAC of 5.1 (range: 0-19.2), a Kujala scale of 85.5 (range: 100-48), an IKDC of 76.6 (range: 100-44.8), and a Tegner score of 4.3 (range: 10-3) with a difference of 0.62 to pre-operative. Patient satisfaction was rated 8.4 (range: 4-10) using a VAS. No loss of reduction, mechanical failure, or implant complications were detected. Radiological follow-up showed no evidence of relevant post-traumatic retropatellar osteoarthritis. In 7 cases, implants were removed due to subjective mechanical irritation. Anatomically contoured patellar plates allow secure fixation of the fracture fragments even in comminuted cases. Especially when tension-band wiring is prone to early failure, locking plate fixation represents a viable option leading to good functional results and low complication rates.

Bulky Selenium Ligand Stabilized Trans-Palladium Dichloride Complexes as Catalyst for Silver-Free Decarboxylative Coupling of Coumarin-3-Carboxylic Acids.

This report describes the syntheses of three new trans-palladium dichloride complexes of bulky selenium ligands. These complexes possess a Cl-Pd-Cl rotor spoke attached to a Se-Pd-Se axle. The new ligands and palladium complexes (C1-C3) were characterized with the help of NMR, HRMS, UV-Vis., IR, and elemental analysis. The single-crystal structure of metal complex C2 confirmed a square planar geometry of complex with trans-orientation. The X-ray structure revealed intramolecular secondary interactions (SeCH-Cl) between chlorine of PdCl2 and CH2 proton of selenium ligand. Variable-temperature NMR data shows coalescence of diastereotopic protons, which indicates pyramidal inversion of selenium atom at elevated temperature. The relaxed potential energy scan of C2 suggests a rotational barrier of ∼12.5 kcal/mol for rotation of chlorine atom through Cl-Pd-Cl rotor. The complex C3 possesses dual intramolecular secondary interactions (OCH2 -Cl and SeCH2 -Cl) with stator ligand. Molecular rotor C2 was found to be a most efficient catalyst for the decarboxylative Heck-coupling under mild reaction conditions. The protocol is applicable to a broad range of substrates with large functional group tolerance and low catalyst loading (2.5 mol %). The mechanism of decarboxylative Heck-coupling reaction was investigated through experimental and computational studies. Importantly the reaction works under silver-free conditions which reduces the cost of overall protocol. Further, the catalyst also worked for decarboxylative arylation and decarboxylative Suzuki-Miyaura coupling reactions with good yields of the coupled products.

DISTAL FEMORAL FRACTURES FROM HIGH-ENERGY TRAUMA: A RETROSPECTIVE REVIEW OF COMPLICATION RATE AND RISK FACTORS.

Determine complications' incidence and risk factors in high-energy distal femur fractures fixed with a lateral locked plate. Forty-seven patients were included; 87.2% were male, and the average age was 38.9. The main radiographic parameters collected were distal lateral femoral angle (DFA), distal posterior femoral angle (DPLF), comminution length, plate length, screw working length, bone loss, and medial contact after reduction and plate-bone contact, location of callus formation, and implant failure. The complications recorded were nonunion, implant failure, and infection. Complex C2 and C3 fractures accounted for 85.1% of cases. Open fractures accounted for 63.8% of cases. The mean AFDL and AFDP were 79.8 4.0 and 79.3 6.0, respectively. The average total proximal and distal working lengths were 133.3 42.7, 60.4 33.4, and 29.5 21.8 mm, respectively. The infection rate was 29.8%, and the only risk factor was open fracture (p = 0.005). The nonunion rate was 19.1%, with longer working length (p = 0.035) and higher PDFA (p = 0.001) as risk factors. The site of callus formation also influenced pseudoarthrosis (p = 0.034). High-energy distal femoral fractures have a higher incidence of pseudoarthrosis and infection. Nonunion has greater working length, greater AFDL, and absence of callus formation on the medial and posterior sides as risk factors. The risk factor for infection was an open fracture. Level of Evidence III; Retrospective Cohort Study .

Utilization of Guanidine-Based Ancillary Ligands in Arene-Ruthenium Complexes for Selective Cytotoxicity.

A family of three water-soluble half-sandwich arene–ruthenium complexes, depicted as C1–C3, having the general formula [Ru(p-cymene)(L)Cl]Cl has been synthesized, where L represents (1H-benzo[d]imidazol-2-yl)guanidine (L1) or (benzo[d]oxazol-2-yl)guanidine (L2) or (benzo[d]thiazol-2-yl)guanidine (L3). The crystal structure of complex C3 has been determined. The complexes show several absorption bands in the visible and ultraviolet regions, and they also show prominent emission in the visible region while excited near 400 nm. Studies on the interaction of ligands L1–L3 and complexes C1–C3 with calf thymus DNA reveal that the complexes are better DNA binders than the ligands, which is attributable to the imposed planarity of the ruthenium-bound guanidine-based ligand, enabling it to serve as a better intercalator. Molecular docking studies show that the complexes effectively bind with DNA through electrostatic and H-bonding interactions and partial intercalation of the guanidine-based ligands. Cytotoxicity studies carried out on two carcinoma cell lines (PC3 and A549) and on two non-cancer cell lines (BPH1 and WI-38) show a marked improvement in antitumor activity owing to complex formation, which is attributed to improvement in cellular uptake on complex formation. The C1 complex is found to exhibit the most prominent activity against the PC3 cell line. Inclusion of the guanidine-based ligands in the half-sandwich ruthenium–arene complexes is found to be effective for displaying selective cytotoxicity to cancer cells and also for convenient tracing of the complexes in cells due to their prominent emissive nature.

Thermostable α-Diimine Nickel Complexes with Substituents on Acenaphthequinone-backbone for Ethylene Polymerization

In order to promote the thermostability of α-diimine nickel complex by ligand backbone structure, a series of α-diimine nickel complexes with substituents on acenaphthequinone backbone were synthesized and used as catalysts for ethylene polymerization. When the hydroxyethyl phenoxyl group was introduced to the acenaphthequinone-backbone, the thermal stability and activity of the catalyst could be significantly improved. The catalytic activity of complex C2 [5-(4-(2-hydroxyethyl)phenoxyl)-N,N-bis(2,6-diisopropyl)acenaphthylene-1,2-diimine]nickel(II) dibromide with isopropyl substituents on N-aryl reached 8.2 × 106 g/(molNi·h) at 70 °C and 2 MPa. The activity of [5-(4-(2-hydroxyethyl)phenoxyl)-N,N-bis(2,6-dibenzhydryl-4-menthylphenyl)acenaphthylene-1,2-diimine]nickel(II) dibromide (C3) still maintained at 6.7 × 105 g/(molNi·h) at 120 °C. Compared with C3 containing bulky dibenzhydryl substituents, the activity of C2 was sensitive to the change of the polymerization pressure. However, the polyethylenes obtained from complex C3 had lower branching density. Meanwhile, the molecular weight could reach 971 kg/mol, which is almost 5 times as much as that of the polyethylene obtained from complex C2.

P0385CLINICAL DIFFERENCES OF MEMBRANOPROLIFERATIVE GLOMERULONEPHROPATHY (MPGN) ACCORDING TO PRESENCE OF HEPATITIS B VIRUS INFECTION

Abstract Background and Aims Traditional definition of MPGN by morphologic changes on light microscopic examination was reclassified into MPGN caused by immunoglobulin/immune complex injury and C3 glomerulopathy (C3G) with alternative complement pathway abnormality based on immunofluorescence staining. MPGN might be caused by various causes such as malignancy, infection, autoimmune diseases, etc. It was rarely known the clinical characteristics of MPGN according to the possible causes excluding C3G. Method We enrolled 20,481 adult patients having native kidney biopsy for diagnosis of nephritis between 1979 and 2018, retrospectively. Among them, there were 553 patients with MPGN whom we reclassified into 18 patients with C3G and 535 MPGN patients. We excluded patients with cancer, autoimmune disease, hepatitis C virus infection, C3G, or combined pathologic diagnosis other than MPGN. Finally, we enrolled 156 patients without hepatitis B surface antigen (HBsAg)[MPGN] and 48 patients with HBsAg [MPGN_HBV]. The final outcomes were incidences of end stage renal disease (ESRD) and death. Results Patients with MPGN_HBV are younger than MPGN (45.5 ± 15.8 years vs 54.6 ± 15.7 years, p=0.001) and included more males (43 (89.6%) vs 97 (62.2%), p&amp;lt;0.001). The systolic blood pressure was not different between groups but the diastolic blood pressure was higher in MPGN_HBV (85.4 ± 10.4 mmHg vs 80.7 ± 13.4 mmHg, p=0.018). The level of urine protein to creatinine ratio was not different between groups but the level of glomerular filtration rate (GFR) was higher in patients with MPGN_HBV compared to patients with MPGN (65.8 ± 29.0 ml/min/1.73 m2 vs 57.5 ± 34.8 ml/min/1.73 m2, p=0.039). Mortality was observed in 2 patients with MPGN_HBV (4.2 %) and 9 patients with MPGN (5.8%)(p=1.000) during 64.9 months (median). Incident ESRD was notified in 6 patients with MPGN_HBV (13.3 %) and 39 patients with MPGN (26.5 %)(p=0.067) during 47.8 months (median). HBV positivity was not a risk factor to mortality (p=0.847) and was not a risk factor to incident ESRD (p=0.108), either, by Cox’s hazard proportional model adjusted with related factors to mortality. The most important risk factor was hemoglobin and GFR at renal biopsy. Conclusion The clinical characteristics of MPGN according to presence of HBsAg were different, however, the prognosis was not dependent on HBsAg positivity, which suggested the severity of renal injury was more important than the cause of renal injury.

Coordination properties of two new Schiff-base phenoxy-carboxylates and comparative study of their antioxidant activities

Two novel tridentate Schiff-base ligands containing carboxylate groups were obtained from the condensation of 3-amino-4-hydroxybenzoic acid with either acetylacetone (H3L1) or salicylaldehyde (H3L2). H3L1 reacted with copper(II) acetate and pyridine (strongly coordinating solvent) to afford the C1 complex, while reaction of H3L2 with nickel(II) acetate and pyridine afforded two types of complexes C2 and C3. The two ligands and their metal complexes were fully characterized by elemental analysis, XRD and spectroscopic analysis. Upon its fully deprotonated state, (L1)3− coordinates in a keto-enamine fashion and acts as a ditopic binder through an ONO tridentate donor system and an O monodentate donor system (carboxylate). Upon its doubly deprotonated state, (HL2)2− ligand acts either as monotopic tridentate binder (i.e. enol-imine form with an ONO donor system that lead to complex C2) or as a ditopic ligand (ONO tridentate and O monodentate donor systems to afford complex C3). The molecular structure of all the compounds were determined by single crystal X-ray diffraction studies and revealed several important characteristics. In complex C1, the Cu(II) cations are five-coordinated with a slightly distorted square pyramidal geometry, while in C2 and C3 complexes, the Ni(II) ions are four and six–coordinated with a square planar and a slightly distorted octahedral geometry, respectively. Following this structural investigation, the antioxidant activities of the free ligands and their metal complexes were then investigated and demonstrated interesting antioxidant features especially for H3L2 and complex C3. Lastly, temperature dependent magnetic susceptibility measurements showed the presence of ferromagnetic interactions in C1 mediated through the phenoxido bridges.

The glomerular crescent: triggers, evolution, resolution, and implications for therapy.

Purpose of reviewCrescents are classical histopathological lesions found in severe forms of rapidly progressive glomerulonephritis, also referred to as crescentic glomerulonephritis (CGN). Crescent formation is a consequence of diverse upstream pathomechanisms and unraveling these mechanisms is of great interest for improving the management of patients affected by CGN. Thus, in this review, we provide an update on the latest insight into the understanding on how crescents develop and how they resolve.Recent findingsCellular crescents develop from activated parietal epithelial cells (PECs) residing along Bowman's capsule and their formation has as a consequence the decline in glomerular filtration rate (GFR). Cellular crescents can be reversible, but when multilevel growth of PECs associate with an epithelial--mesenchymal transition-like change in cell phenotype, fibrous crescents form, and crescents become irreversible also in terms of GFR recovery. Different molecular pathways trigger the activation of PECs and are a prime therapeutics target in CGN. First, crescent formation requires also vascular injury causing ruptures in the glomerular basement membrane that trigger plasmatic coagulation within Bowman's space. This vascular necrosis can be triggered by different upstream mechanisms, such as small vessel vasculitides, immune complex glomerulonephritis, anti-GBM disease, and C3 glomerulonephritis, that all share complement activation but involve diverse upstream immune mechanisms outside the kidney accessible for therapeutic intervention.SummaryKnowing the upstream mechanisms that triggered crescent formation provides a tool for the development of therapeutic interventions for CGN.

Synthesis, characterization, and antitumor activity of novel tumor‐targeted platinum(IV) complexes

Four tumor‐targeted platinum(IV) complexes with ammonia and cyclohexylamine as the carrier groups and biotin as the axial group were designed, synthesized, and characterized. In vitro evaluation of the antitumor activity of complexes C1–C4 against lung cancer cells (A549), liver cancer cells (SMMC‐7721), breast cancer cells (MCF‐7), and colon cancer cells (SW480) was carried out. Complex C3 had the best cellular activity. Compared with cisplatin, complex C3 showed good anticancer activity against A549 cell line,complex C3 (6.34±0.44) is 3 times more cytotoxic than cisplatin (19.40±0.71),and against MCF‐7 cell line complex C3 (4.22±0.11) is 5.4 times more cytotoxic than cisplatin (22.96±0.58), and against SW480 cell line complex C3 (6.65±0.60) is 3.4 times more cytotoxic than cisplatin (23.15±0.22). (Table 1) Axial chloride increased the redox power of complex C3 to increase the intercellular accumulation and the introduction of mixed amine had the ability to overcome cisplatin resistance. Complex C3 works best on MCF‐7, then SW480, A549, and SMMC‐7721. Thus, complex C3 is targeted by the axial introduction of biotin.

Synthesis, characterization and antibacterial activity studies of new 2-pyrral-L-amino acid Schiff base palladium (II) complexes

Three new 2-pyrral amino acid Schiff base palladium (II) complexes were synthesized, characterized and their activity against six bacterial species was investigated. The ligands: Potassium 2-pyrrolidine-L-methioninate (L1), Potassium 2-pyrrolidine-L-histidinate (L2) and Potassium 2-pyrrolidine-L-tryptophanate (L3) were synthesized and reacted with dichloro(1,5-cyclooctadiene)palladium(II) to form new palladium (II) complexes C1, C2 and C3, respectively. 1H NMR, FTIR, UV–Vis, elemental analysis and conductivity measurements were used to characterize the products. The antibacterial activities of the compounds were evaluated against Gram-positive Staphylococcus aureus (S. aureus, ATCC 25923), methicillin-resistant Staphylococcus aureus (MRSA, ATCC 33591), Staphylococcus epidermidis (S. epidermidis, ATCC 12228) and Streptococcus pyogenes (S. pyogenes, ATCC 19615) and, gram-negative Pseudomonas aeruginosa (P. aeruginosa, ATCC 27853) and Klebsiella pneumoniae (K. pneumoniae, ATCC 13883) using the agar well diffusion assay and microtitre plate serial dilution method. The palladium complexes were active against the selected bacteria with the imidazole ring containing complex C2 and indole heterocyclic ring containing complex C3 showing the highest activity.

Outcome following swashbuckler modified anterior approach versus lateral approach for management of complex distal femur fractures: A prospective comparative study

Background: Distal femur fractures with intra articular extension and comminution are exacting injuries, rife with complications such as malunion and stiffness. We prospectively evaluated and compared a consecutive series of patients with AO type C distal femur fractures to determine the clinicoradiological outcome after fixation with a single locked plate using swashbuckler approach(modified anterolateral) and standard lateral approach. Materials and Methods:120 patients with C type distal femur fractures (mostly type C2 and C3) were treated with distal femur locking compression plate (DF-LCP), 60 using swashbuckler approach and 60 using standard lateral approach, were included in the study. The clinical outcome at 1 year was determined using the Neer’s Score.Results: All fractures united at a mean of 14.64 weeks (range 12-20 weeks). In our study mean duration of surgery for lateral approach group was greater (99.6min) than swashbuckler group (85min).There were no significant complications such as nonunion, deep infection, and implant failure. Mean ROM in swashbuckler group was 100.83 degree compared to 83.83 in lateral group. Mean Neer’s score was 76.96 in lateral approach group compared to 81.83 Neer’s score in swashbuckler approach. Excellent results were seen in 19 cases (63.3%) in swashbuckler group as compared to 13 cases (43.3%) in lateral approach group.Conclusion: The results of complex C type distal femur fractures, fixed with a single distal femur locking compression plate (DF-LCP) using a swashbuckler approach as compared to standard lateral approach are affirmative and comparable with a majority of patients achieving good to excellent outcome at 1 year especially in complex C3 fractures.

New organoruthenium compounds with pyrido[2',3':5,6]pyrazino[2,3-f][1, 10]phenanthroline: synthesis, characterization, cytotoxicity, and investigation of mechanism of action.

Three new ruthenium(II)-arene complexes with pyrido[2',3':5,6]pyrazino[2,3-f][1, 10]phenanthroline (ppf) of general formula: C1 ([(ƞ6-benzene)Ru(ppf)Cl]PF6, C2 ([(ƞ6-toluene)Ru(ppf)Cl]PF6) and C3 ([(ƞ6-p-cymene)Ru(ppf)Cl]PF6) have been synthesized. The structures of complexes were determined by elemental analysis, IR, ESI-MS, as well as with 1H and 13C NMR spectroscopy. Cytotoxic activity has been evaluated in three different human neoplastic cell lines (A549, A375, LS 174T) and in one human non-tumor cell line (MRC-5), by the MTT assay. Complexes C1-C3 showed IC50 values in the micromolar range below 100µM. Complex C3, carrying ƞ6-p-cymene as the arene ligand, exhibited cytoselective activity toward human malignant melanoma A375 cells (IC50 = 15.8 ± 2.7µM), and has been selected for further analyses of its biological effects. Drug-accumulation study performed in the A375 cells disclosed that C3 possess lower ability of entering the cells compared to cisplatin and distributes approximately equally in the cytosol and membrane/organelle fraction of cells. Investigations in the 3D model of A375 cells, disclosed different effects of the complex C3 and cisplatin on growth of multicellular tumor spheroids (MCTSs). While the size of cisplatin-treated MCTSs decreased with time, MCTSs treated with C3 continued to growth. Differences in structural organization and biological activity of this type of ruthenium(II)-arene complexes versus cisplatin in A375 malignant melanoma cells pointed out their different modes of action, and necessity for further biological studies and optimizations for potential applications.