Precursor Cis Research Articles

Hormones metabolism as affected by LED blue light in citrus fruit

The LED Blue Light (LBL) (450 nm) effect on hormones levels and on jasmonates (JAs) metabolism in oranges was investigated. The quantum flux (2 days, 60 μmol m−2. s−1) was chosen for its efficacy in reducing postharvest rot caused by this crop's main postharvest phytopathogenic fungus (Penicillium digitatum). The analysis of abscisic (ABA), salicylic (SA) and indole-3-acetic (IAA) acids, and of JAs-related metabolites, revealed that LBL modifies all studied metabolites and had major effects on JAs levels, mainly on jasmonic acid (JA) and its precursor cis-(+)-12-oxo-phytodienoic acid (OPDA). This agrees with the up-regulation of the genes participating in their synthesis. Results highlight the relevance of CsLOX1 and CsLOX5, and the contribution of CsAOC3, in the LBL-induced OPDA biosynthesis, whereas CsOPR2, CsACX1 and CsACX3 would play a part in the synthesis of JA from OPDA. Data also suggest that the applied LBL quantum flux favors fruit JA perception by increasing the expression of the coronatine insensitive 1 (COI1) receptor; and signaling by down-regulating abundant CsJAZ negative regulators. Differences in OPDA and JA between the LBL-treated oranges and their control fruit left in the dark disappeared after shifting the LBL-treated oranges to darkness for 3 more days. However, the LBL and darkness combination slightly increased IAA and SA contents.

Cyclometalated ruthenium complexes overcome cisplatin resistance through PI3K/mTOR/Nrf2 signaling pathway.

Currently, cisplatin resistance remains a primary clinical obstacle in the successful treatment of non-small cell lung cancer. Here, we designed, synthesized, and characterized two novel cyclometalated Ru(II) complexes, [Ru(bpy)2(1-Ph-7-OCH3-IQ)] (PF6) (bpy=2,2'-bipyridine, IQ=isoquinoline, RuIQ7)and [Ru(bpy)2(1-Ph-6,7-(OCH3)2-IQ)] (PF6) (RuIQ8). As experimental controls, we prepared complex [Ru(bpy)2(1-Ph-IQ)](PF6) (RuIQ6) lacking a methoxy group in the main ligand. Significantly, complexes RuIQ6-8 displayed higher in vitro cytotoxicity when compared to ligands, precursor cis-[Ru(bpy)2Cl2], and clinical cisplatin. Mechanistic investigations revealed that RuIQ6-8 could inhibit cell proliferation by downregulating the phosphorylation levels of Akt and mTOR proteins, consequently affecting the rapid growth of human lung adenocarcinoma cisplatin-resistant cells A549/DDP. Moreover, the results from qRT-PCR demonstrated that these complexes could directly suppress the transcription of the NF-E2-related factor 2 gene, leading to the inhibition of downstream multidrug resistance-associated protein 1 expression and effectively overcoming cisplatin resistance. Furthermore, the relationship between the chemical structures of these three complexes and their anticancer activity, ability to induce cell apoptosis, and their efficacy in overcoming cisplatin resistance has been thoroughly examined and discussed. Notably, the toxicity test conducted on zebrafish embryos indicated that the three Ru-IQ complexes displayed favorable safety profiles. Consequently, the potential of these developed compounds as innovative therapeutic agents for the efficient and low-toxic treatment of NSCLC appears highly promising.

Ligand-Centered Photocatalytic Hydrogen Production in an Axially Capped Rh2(II,II) Paddlewheel Complex with Red Light.

A new series of Rh2(II,II) complexes with the formula cis-[Rh2(DTolF)2(bpnp)(L)]2+, where bpnp = 2,7-bis(2-pyridyl)-1,8-naphthyridine, DTolF = N,N'-di(p-tolyl) formamidinate, and L = pdz (pyridazine; 2), cinn (cinnoline; 3), and bncn (benzo[c]cinnoline; 4), were synthesized from the precursor cis-[Rh2(DTolF)2(bpnp)(CH3CN)2]2+ (1). The first reduction couple in 2-4 is localized on the bpnp ligand at approximately -0.52 V vs Ag/AgCl in CH3CN (0.1 M TBAPF6), followed by reduction of the corresponding diazine ligand. Complex 1 exhibits a Rh2(δ*)/DTolF → bpnp(π*) metal/ligand-to-ligand charge-transfer (1ML-LCT) absorption with a maximum at 767 nm (ε = 1800 M-1 cm-1). This transition is also present in the spectra of 2-4, overlaid with the Rh2(δ*)/DTolF → L(π*) 1ML-LCT bands at 516 nm in 2 (L = pdz), 640 nm in 3 (L = cinn), and 721 nm in 4 (L = bncn). Complexes 2 and 3 exhibit Rh2(δ*)/DTolF → bpnp 3ML-LCT excited states with lifetimes, τ, of 3 and 5 ns, respectively, in CH3CN, whereas the lowest energy 3ML-LCT state in 4 is Rh2(δ*)/DTolF → bncn in nature with τ = 1 ns. Irradiation of 4 with 670 nm light in DMF in the presence of 0.1 M TsOH (p-toluene sulfonic acid) and 30 mM BNAH (1-benzyl-1,4-dihydronicotinamide) results in the production of H2 with a turnover number (TON) of 16 over 24 h. The axial capping of the Rh2(II,II) bimetallic core with the bpnp ligand prevents the formation of an Rh-H hydride intermediate. These results show that the observed photocatalytic reactivity is localized on the bncn ligand, representing the first example of ligand-centered H2 production.

1,2-Azolylamidino ruthenium(II) complexes with DMSO ligands: electro- and photocatalysts for CO2 reduction.

New 1,2-azolylamidino complexes fac-[RuCl(DMSO)3(NHC(R)az*-κ2N,N)]OTf [R = Me (2), Ph (3); az* = pz (pyrazolyl, a), indz (indazolyl, b)] are synthesized via chloride abstraction from their corresponding precursors cis,fac-[RuCl2(DMSO)3(az*H)] (1) after subsequent base-catalyzed coupling of the appropriate nitrile with the 1,2-azole previously coordinated. All the compounds are characterized by 1H NMR, 13C NMR and IR spectroscopy. Those derived from MeCN are also characterized by X-ray diffraction. Electrochemical studies showed several reduction waves in the range of -1.5 to -3 V. The electrochemical behavior in CO2 media is consistent with CO2 electrocatalytic reduction. The catalytic activity expressed as [icat(CO2)/ip(Ar)] ranged from 1.7 to 3.7 for the 1,2-azolylamidino complexes at voltages of ca. -2.7 to -3 V vs. ferrocene/ferrocenium. Controlled potential electrolysis showed rapid decomposition of the Ru catalysts. Photocatalytic CO2 reduction experiments using compounds 1b, 2b and 3b carried out in a CO2-saturated MeCN/TEOA (4 : 1 v/v) solution containing a mixture of the catalyst and [Ru(bipy)3]2+ as the photosensitizer under continuous irradiation (light intensity of 150 mW cm-2 at 25 °C, λ > 300 nm) show that compounds 1b, 2b and 3b allowed CO2 reduction catalysis, producing CO and trace amounts of formate. The combined turnover number for the production of formate and CO is ca. 100 after 8 h and follows the order 1b < 2b ≈ 3b.

Synthesis, structure and characterisation of late transition metal complexes with 2-(tetrazol-1-yl)pyridine

Complexes [MII(2-pytz)Cl2] (M(II) = Pt, Pd; 2-pytz = 2-(tetrazol-1-yl)pyridine) were synthesised via direct interaction of the corresponding metal chlorides (K2PtCl4 or PdCl2) with 2-pytz under ambient conditions. RuCl3 does not react with 2-pytz under reflux in the protic media, while under reflux in N, N-dimethylformamide in the presence of LiCl, decomposition of the tetrazole cycle occurred leading to the formation of Ru(III)-coordinated N, N-dimethyl-N ′-(pyridin-2-yl)formimidamide derivative Li[RuIII(Py — N =C — NMe2)2Cl2]. The complex [Ru(2-pytz)(DMSO)3Cl2] ⋅ MeOH, where DMSO is dimethyl sulfoxide, was synthesised by reacting a specially prepared precursor cis-[Ru(DMSO)4Cl2] with 2-pytz in methanol under reflux conditions. The complex [Ru(2-pytz)(DMSO)2Cl2] was synthesised by reacting cis-[Ru(DMSO)4Cl2] with 2-pytz in ethanol under reflux conditions. The resulting complexes were characterised by elemental analyses, electrospray ionisation mass-spectrometry with detection of positive and negative ions, infrared spectroscopy, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, and simultaneous thermal analysis. The structures of complexes [Pd(2-pytz)Cl2] and [Ru(2-pytz)(DMSO)3Cl2] ⋅ MeOH were investigated by single-crystal X-ray analysis. In the former, 2-pytz shows a N,N-chelating coordination via the pyridine ring N and the tetrazole ring N2 atoms. In the latter, 2-pytz coordinates as a monodentate ligand via the tetrazole ring N4 atom. According to 1H NMR spectroscopy data, in complex [Ru(2-pytz)(DMSO)2Cl2], 2-pytz coordinates as a N, N-chelating ligand via the pyridine ring N and the tetrazole ring N2 atoms.

Repurposing potential of rimantadine hydrochloride and development of a promising platinum(II)-rimantadine metallodrug for the treatment of Chikungunya virus infection

Most of the patients infected with Chikungunya virus (CHIKV) develop chronic manifestations characterized by pain and deformity in joints, impacting their quality of life. The aminoadamantanes, in their turn, have been exploited due to their biological activities, with amantadine and memantine recently described with anti-CHIKV activities. Here we evaluated the antiviral activity of rimantadine hydrochloride (rtdH), a well-known antiviral agent against influenza A, its platinum complex (Pt-rtd), and the precursor cis-[PtCl2(dmso)2], against CHIKV infection in vitro. The rtdH demonstrated significant antiviral activity in all stages of CHIKV replication (29% in pre-treatment; 57% in early stages of infection; 60% in post-entry stages). The Pt-rtd complex protected the cells against infection in 92%, inhibited 100% of viral entry, mainly by a virucidal effect, and impaired 60% of post-entry stages. Alternatively, cis-[PtCl2(dmso)2] impaired viral entry in 100% and post-entry steps in 60%, but had no effect in protecting cells when administered prior to CHIKV infection. Collectively, the obtained data demonstrated that rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, with the strongest effect observed to Pt-rtd complex, which reduced up to 100% of CHIKV infection. Moreover, molecular docking analysis and infrared spectroscopy data (ATR-FTIR) suggest an interaction of Pt-rtd with CHIKV glycoproteins, potentially related to the mechanism of inhibition of viral entry by Pt-rtd. Through a migration retardation assay, it was also shown that Pt-rtd and cis-[PtCl2(dmso)2] interacted with the dsRNA in 87% and 100%, respectively. The obtained results highlight the repurposing potential of rtdH as an anti-CHIKV drug, as well as the synthesis of promising platinum(II) metallodrugs with potential application for the treatment of CHIKV infections.Importance Chikungunya fever is a disease that can result in persistent symptoms due to the chronic infection process. Infected patients can develop physical disability, resulting and high costs to the health system and significant impacts on the quality of life of affected individuals. Additionally, there are no licensed vaccines or antivirals against the Chikungunya virus (CHIKV) and the virus is easily transmitted due to the abundance of viable vectors in epidemic regions. In this context, our study highlights the repurposing potential of the commercial drug rimantadine hydrochloride (rtdH) as an antiviral agent for the treatment of CHIKV infections. Moreover, our data demonstrated that a platinum(II)-rimantadine metallodrug (Pt-rtd) poses as a potent anti-CHIKV molecule with potential application for the treatment of Chikungunya fever. Altogether, rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, reducing up to 100% of CHIKV infection in vitro.

The jasmonate biosynthesis Gene OsOPR7 can mitigate salinity induced mitochondrial oxidative stress

Salinity poses a serious threat to global agriculture and human food security. A better understanding of plant adaptation to salt stress is, therefore, mandatory. In the non-photosynthetic cells of the root, salinity perturbs oxidative balance in mitochondria, leading to cell death. In parallel, plastids accumulate the jasmonate precursor cis (+)12-Oxo-Phyto-Dienoic Acid (OPDA) that is then translocated to peroxisomes and has been identified as promoting factor for salt-induced cell death as well. In the current study, we probed for a potential interaction between these three organelles that are primarily dealing with oxidative metabolism. We made use of two tools: (i) Rice OPDA Reductase 7 (OsOPR7), an enzyme localised in peroxisomes converting OPDA into the precursors of the stress hormone JA-Ile. (ii) A Trojan Peptoid, Plant PeptoQ, which can specifically target to mitochondria and scavenge excessive superoxide accumulating in response to salt stress. We show that overexpression of OsOPR7 as GFP fusion in tobacco (Nicotiana tabacum L. cv. Bright Yellow 2, BY-2) cells, as well as a pretreatment with Plant PeptoQ can mitigate salt stress with respect to numerous aspects including proliferation, expansion, ionic balance, redox homeostasis, and mortality. This mitigation correlates with a more robust oxidative balance, evident from a higher activity of superoxide dismutase (SOD), lower levels of superoxide and lipid peroxidation damage, and a conspicuous and specific upregulation of mitochondrial SOD transcripts. Although both, Plant PeptoQ and ectopic OsOPR7, were acting in parallel and mostly additive, there are two specific differences: (i) OsOPR7 is strictly localised to the peroxisomes, while Plant PeptoQ found in mitochondria. (ii) Plant PeptoQ activates transcripts of NAC, a factor involved in retrograde signalling from mitochondria to the nucleus, while these transcripts are suppressed significantly in the cells overexpressing OsOPR7. The fact that overexpression of a peroxisomal enzyme shifting the jasmonate pathway from the cell-death signal OPDA towards JA-Ile, a hormone linked with salt adaptation, is accompanied by more robust redox homeostasis in a different organelle, the mitochondrion, indicates that cross-talk between peroxisome and mitochondrion is a crucial factor for efficient adaptation to salt stress.

Scavenging capacity and cytotoxicity of new Ru(II)-diphosphine/α-amino acid complexes

Reaction of α-amino acids (HL) with the precursor cis-[RuCl2(dppe)2] [HL = tyrosine (Tyr) or serine (Ser); dppe = 1,2-bis(diphenylphosphino)ethane] afforded the complexes [Ru(L−)(dppe)2]Cl {[Ru(Tyr-)(dppe)2]Cl (1) and [Ru(Ser-)(dppe)2]Cl (2)}. The new ruthenium complexes, with formulae [Ru(Tyr-)(dppe)2]Cl (1) and [Ru(Ser-)(dppe)2]Cl (2) were synthesized and characterized on the basis of elemental analysis, molar conductivity, IR/UV–Vis and 31P{1H} NMR spectra. The in vitro cytotoxicities of the complexes against the MDA-MB-231 (breast adenocarcinoma) cell line were determined by the MTT assay. Complexes (1) and (2) show good cytotoxicity profiles against the MDA-MB-231 cell line with IC50 values of 2.05 ± 0.71 μM and 5.64 ± 0.72 μM, respectively, which are in the same order of values obtained for the metallodrug cisplatin (2.44 ± 0.20 μM) in the same assay. The selectivity indexes were significant for both complexes, showing lower cytotoxicity activity against the non-tumor breast cell line MCF-10A, with SI of 5.0 and 3.2, respectively. In addition, the lipophilicities of these complexes were determined and their interactions with human serum albumin (HSA) protein were investigated by fluorescence. The lipophilicities of the complexes suggest that this property has a significant effect on their cytotoxicity and the interaction measurements of the complexes with HSA indicate that the static fluorescence quenching mechanism is the main one involved in the formation of (1)-HSA and (2)-HSA adducts. Moreover, Van der Waalś interactions and hydrogen bonds in (1)-HSA and electrostatic interaction in (2)-HSA are the predominant intermolecular forces between the complexes and the biomolecule. Furthermore, the antioxidant activity of the complexes was determined using the superoxide radical scavenging method, in vitro. Complex (1) was found to present a higher antioxidative activity, showing to be better than the standard antioxidant, vitamin C. In vivo toxicity assessment on zebrafish embryos showed that although the higher concentration of complex (1) has caused lethality of embryos, the effects of the concentration equivalent to the IC50 of complex (1) and cisplatin were similar in the hatching rate, mortality rate and morphological changes, showing a potential of complex (1) as a new anticancer agent.

Stereoisomeric Control in [RuCl2(PTA)2(2L)] Complexes (2L=2py or bpy): From Theoretical Calculations to a 2+2 Metallacycle of Pyridylporphyrins

AbstractTreatment of the Ru(II) precursor cis,cis,trans‐[RuCl2(dmso‐S)2(PTA)2] (1, PTA=1,3,5‐triaza‐7‐phosphaadamantane) with 2,2′‐bipyridine (bpy) in refluxing ethanol selectively affords cis,cis‐[Ru(bpy)Cl2(PTA)2] (2), whereas with pyridine (py), under the same conditions, it gives trans,cis,cis‐[RuCl2(PTA)2(py)2] (6). The slightly less stable stereoisomer of 2, cis,trans‐[Ru(bpy)Cl2(PTA)2] (3), is obtained selectively through a different synthetic route. Isomers 2 and 3 are thermally stable, but cleanly equilibrate upon irradiation of an aqueous solution of either one with blue light. Intrigued by the stereoisomeric outcome in the preparations of this homogeneous set of complexes, we also investigated 2, 3, and 6 (and the mono‐pyridine complex trans,mer‐[RuCl2(py)(PTA)3] (7)) through a topological analysis of the electron density map using the quantum theory of atoms in molecules (QTAIM). The wealth of acquired experimental and calculated data allow us to discuss the stereochemical preferences of the [RuCl2(PTA)2(2 L)] complexes (2 L=bpy or 2py) in terms of electronic and steric contributions. The results of this speculative study on model complexes are transferable to similar systems. As an example, our findings from the reactivity of 1 towards pyridine allowed us to prepare the 2+2 pyridylporphyrin metallacycle trans,cis,cis‐[RuCl2(PTA)2(4′‐cisDPyP)]2 (10, 4′‐cisDPyP=5,10‐(4′‐pyridyl)‐15,20‐(phenyl)‐porphyrin), whose X‐ray molecular structure is also reported.

Synthesis, spectroscopic characterization and computational study of Ru(II)/DMSO complexes with monocoordinated carbazate ligands

Reaction of the precursor cis,fac-[RuCl2(dmso-S)3(dmso-O)] with three carbazate ligands led to new compounds of the type cis,fac-[RuCl2(dmso-S)3(L)] (L = benzylcarbazate (bc), 1; 4-methoxybenzylcarbazate (mc), 2; or 3,5-dimethoxy-α,α-dimethylbenzylcarbazate (mmc), 3). Complexes 1–3 have been characterized by elemental analysis (CHN), FTIR, UV–vis, and 1H and 13C{1H} NMR spectroscopy. Complex 1 was also analyzed by single-crystal X-ray diffraction and theoretical calculations were performed in order to better understand its spectroscopic data and electronic structure. All collected data were consistent with substitution of one dmso ligand by a monodentate carbazate ligand. Preliminary biological assays against breast and prostate human cancer cell lines were performed in order to evaluate the cytotoxic activity of these three new complexes.

Increased ROS generation causes apoptosis-like death: Mechanistic insights into the anti-Leishmania activity of a potent ruthenium(II) complex

Some metallodrugs that exhibit interesting biological activity contain transition metals such as ruthenium, and have been extensively exploited because of their antiparasitic potential. In previous study, we reported the remarkable anti-Leishmania activity of precursor cis-[RuIICl2(dppm)2], where dppm = bis(diphenylphosphino)methane, and new ruthenium(II) complexes, cis-[RuII(η2-O2CC10H13)(dppm)2]PF6 (bbato), cis-[RuII(η2-O2CC7H7S)(dppm)2]PF6 (mtbato) and cis-[RuII(η2-O2CC7H7O2)(dppm)2]PF6 (hmxbato) against some Leishmania species. In view of the promising activity of the hmxbato complex against Leishmania (Leishmania) amazonensis promastigotes, the present work investigated the possible parasite death mechanism involved in the action of this hmxbato and its precursor. We report, for the first time, that hmxbato and precursor promoted an increase in reactive oxygen species production, depolarization of the mitochondrial membrane, DNA fragmentation, formation of a pre-apoptotic peak, alterations in parasite morphology and formation of autophagic vacuoles. Taken together, our results suggest that these ruthenium complexes cause parasite death by apoptosis. Thus, this work provides relevant knowledge on the activity of ruthenium(II) complexes against L. (L.) amazonensis. Such information will be essential for the exploitation of these complexes as future candidates for cutaneous leishmaniasis treatment.

Pyridyl based ruthenium(II) catalyst precursors and their dihydride analogues as the catalytically active species for the transfer hydrogenation of ketones

In this study we describe the one-pot and high yield synthesis of the ruthenium(II) complex cis-dichloride [RuCl2(PPh3)2(L1)] (L1 = 4-methyl-2-(2′-pyridyl)quinoline) (1). The solid state structure of L1 is described. The catalytic activity of 1 in the transfer hydrogenation of various ketones by 2-propanol at 82 °C, has been studied and compared with the activity of the known catalyst precursors cis-[RuCl2(PPh3)2(L2)] (L2 = 2-(2'-pyridyl)quinoline) (2), cis-[RuCl2(PPh3)2(L3)] (L3 = 2-(2′-pyridyl)quinoxaline) (3) and cis-[RuCl2(PPh3)2(bipy)] (bipy = 2,2′-bipyridine) (4). The ruthenium monohydride complex [RuHCl(PPh3)2(L3)] 3-H (Cl cis to H) was prepared from the reaction of 3 with 2.5 equivalents of a KOiPr solution. Reaction of 3 with 10 equivalents of KOiPr yields the cis-[RuH2(PPh3)2(L3)] (3-H2). Treatment of 1, 2 and 4 with KOiPr (in excess) affords the ruthenium cis-dihydride complexes [RuH2(PPh3)2(L1)] (1-H2), [RuH2(PPh3)2(L2)] (2-H2) and [RuH2(PPh3)2(bipy)] (4-H2). The formation of 1-H2, 2-H2, 3-H2 and 4-H2 is supported by NMR spectroscopic data. The cis-dihydrides 1-H2 to 4-H2 catalyze successfully the transfer hydrogenation of benzophenone to benzhydrol in the absence of a base, suggesting that presumably the active catalyst is a ruthenium dihydride complex (RuH2). Catalyst 1 has been potentially recovered and reused at least four times.

Molybdenum(0) tricarbonyl and tetracarbonyl complexes with a cationic pyrazolylpyridine ligand: synthesis, crystal structures and catalytic performance in olefin epoxidation.

The synthesis of molybdenum(0) tricarbonyl and tetracarbonyl complexes of the form [Mo(CO)3(ptapzpy)Br] (1) and cis-[Mo(CO)4(ptapzpy)]Br (2) is reported, where ptapzpy = 2-(1-propyltrimethylammonium-3-pyrazolyl)pyridine. Preparation of these derivatives was accomplished either through thermal replacement of CO in Mo(CO)6 (for 1) or substitution under milder conditions of piperidine ligands in the precursor cis-[Mo(CO)4(pip)2] (for 2). The crystal structures of the ligand [ptapzpy]Br and complexes 1 and 2 were determined. Thermal treatment of 2 at 125–150 °C leads to mono decarbonylation and formation of 1. On the other hand, oxidative decarbonylation of 1 and 2 by reaction with tert-butylhydroperoxide (TBHP, 10 equiv.) gives a molybdenum oxide hybrid material formulated as [Mo3O9([ptapzpy]Br)2]·nH2O (3), which was characterised by FT-IR and Raman spectroscopy, thermogravimetric analysis, and 13C{1H} CP MAS NMR spectroscopy. Compounds 1–3 were effective (pre)catalysts for the epoxidation of cis-cyclooctene at 55 °C with aqueous H2O2 or TBHP (slightly better results were obtained with the former). The characterisation of the Mo-containing solids isolated after the catalytic reaction showed that poorly soluble β-octamolybdate salts, (L)x[Mo8O26], were formed from 1–3 with TBHP and from 1 with H2O2, while soluble oxoperoxo species were formed from 3 with H2O2. These findings helped to explain the different catalytic performances obtained.

Coordinating Ability of the Iminophosphorane Group in ortho‐Carborane Derivatives

The coordinating ability of the nitrogen donor atom of C‐carboranyl iminophosphoranes was studied in different ligand systems. The analysis of organotin derivatives of the unsubstituted iminophosphorane I1 (SnMe3I1 and SnClMe2I1) and the comparison with the non‐carboranyl analog (SnClMe2I3), reveals the reduced donor capacity of the nitrogen atom due to the closo‐carborane group. To promote the coordination of this weak donor atom, new phosphine–iminophosphorane ligands (IP1 and IP2), with an extra –PPh2 group on the other cage carbon atom, were synthesized and structurally characterized. The analysis of the products formed by the reaction of these ligands with the metal precursor cis‐[PdCl2(PhCN)2] reveals that the phosphine group promotes the coordination of the iminophosphorane nitrogen atom, yielding (P, N) chelates. However, this coordination mode activates the closo‐carborane ligands towards deboronation, and the complexes evolve to the nido derivatives in response to the polar solvents. The activation is increased by the presence of extra donor groups, like in the tridentate ligand IP2, with an extra thioether group. The deboronation by coordination of (P, N) bidentate carboranyl ligands has never been reported, although it has been studied for other ligands, especially for chelating carboranyl diphosphines.

Synthesis, Characterization, Cytotoxic Activity, and Interactions with CT-DNA and BSA of Cationic Ruthenium(II) Complexes Containing Dppm and Quinoline Carboxylates.

The complexes cis-[Ru(quin)(dppm)2]PF6 and cis-[Ru(kynu)(dppm)2]PF6 (quin = quinaldate; kynu = kynurenate; dppm = bis(diphenylphosphino)methane) were prepared and characterized by elemental analysis, electronic, FTIR, 1H, and 31P{1H} NMR spectroscopies. Characterization data were consistent with a cis arrangement for the dppm ligands and a bidentate coordination through carboxylate oxygens of the quin and kynu anions. These complexes were not able to intercalate CT-DNA as shown by circular dichroism spectroscopy. On the other hand, bovine serum albumin (BSA) binding constants and thermodynamic parameters suggest spontaneous interactions with this protein by hydrogen bonds and van der Waals forces. Cytotoxicity assays were carried out on a panel of human cancer cell lines including HepG2, MCF-7, and MO59J and one normal cell line GM07492A. In general, the new ruthenium(II) complexes displayed a moderate to high cytotoxicity in all the assayed cell lines with IC50 ranging from 10.1 to 36 µM and were more cytotoxic than the precursor cis-[RuCl2(dppm)2]. The cis-[Ru(quin)(dppm)2]PF6 were two to three times more active than the reference metallodrug cisplatin in the MCF-7 and MO59J cell lines.

OPDA Has Key Role in Regulating Plant Susceptibility to the Root-Knot Nematode Meloidogyne hapla in Arabidopsis.

Jasmonic acid (JA) is a plant hormone that plays important roles in regulating plant defenses against necrotrophic pathogens and herbivorous insects, but the role of JA in mediating the plant responses to root-knot nematodes has been unclear. Here we show that an application of either methyl jasmonate (MeJA) or the JA-mimic coronatine (COR) on Arabidopsis significantly reduced the number of galls caused by the root-knot nematode Meloidogyne hapla. Interestingly, the MeJA-induced resistance was independent of the JA-receptor COI1 (CORONATINE INSENSITIVE 1). The MeJA-treated plants accumulated the JA precursor cis-(+)-12-oxo-phytodienoic acid (OPDA) in addition to JA/JA-Isoleucine, indicating a positive feedback loop in JA biosynthesis. Using mutants in the JA-biosynthetic pathway, we found that plants deficient in the biosynthesis of JA and OPDA were hyper-susceptible to M. hapla. However, the opr3 mutant, which cannot convert OPDA to JA, exhibited wild-type levels of nematode galling. In addition, mutants in the JA-biosynthesis and perception which lie downstream of opr3 also displayed wild-type levels of galling. The data put OPR3 (OPDA reductase 3) as the branch point between hyper-susceptibility and wild-type like levels of disease. Overall, the data suggests that the JA precursor, OPDA, plays a role in regulating plant defense against nematodes.

Homologs of old yellow enzyme in plants

Old Yellow Enzyme (OYE) is a flavin mononucleotide-dependent oxidoreductase. 12-oxophytodienoic acid reductases (OPRs) are OYE homologs and are represented by multigene families in plants. OPRs catalyze the reduction of double bonds in α,β-unsaturated aldehydes or ketones. They belong to the octadecanoid pathway, which converts linolenic acid to jasmonic acid (JA). Individual OPR family members may have distinct functions due to their different substrate specificity, subcellular localization, tissue distribution, and differential regulation of their expression in response to specific environmental cues. Based on their differential preferences for 12-oxophytodienoate (OPDA) stereoisomers, these enzymes are classified into two subgroups: OPRI and OPRII. OPRI enzymes preferentially catalyze the reduction of cis-(−)OPDA over the JA precursor cis-(+)OPDA , and therefore, they are not involved in JA biosynthesis. Although a significant progress has been made to understand the exact physiological roles of OPR enzymes, the function of OPRI subgroup members in plants remains largely unknown. Enzymes belonging to this subgroup are possibly involved in defense responses and signaling. The members of the OPRII subgroup are required for JA biosynthesis because they catalyze the reduction of the JA precursor cis-(+)OPDA. This review will highlight some characteristics of this family in Arabidopsis and other species and discuss the physiological role of OPR family members in plants.

A previously undescribed jasmonate compound in flowering Arabidopsis thaliana – The identification of cis-(+)-OPDA-Ile

Jasmonates (JAs) are plant hormones that integrate external stress stimuli with physiological responses. (+)-7-iso-JA-L-Ile is the natural JA ligand of COI1, a component of a known JA receptor. The upstream JA biosynthetic precursor cis-(+)-12-oxo-phytodienoic acid (cis-(+)-OPDA) has been reported to act independently of COI1 as an essential signal in several stress-induced and developmental processes. Wound-induced increases in the endogenous levels of JA/JA-Ile are accompanied by two to tenfold increases in the concentration of OPDA, but its means of perception and metabolism are unknown. To screen for putative OPDA metabolites, vegetative tissues of flowering Arabidopsis thaliana were extracted with 25% aqueous methanol (v/v), purified by single-step reversed-phase polymer-based solid-phase extraction, and analyzed by high throughput mass spectrometry. This enabled the detection and quantitation of a low abundant OPDA analog of the biologically active (+)-7-iso-JA-L-Ile in plant tissue samples. Levels of the newly identified compound and the related phytohormones JA, JA-Ile and cis-(+)-OPDA were monitored in wounded leaves of flowering Arabidopsis lines (Col-0 and Ws) and compared to the levels observed in Arabidopsis mutants deficient in the biosynthesis of JA (dde2-2, opr3) and JA-Ile (jar1). The observed cis-(+)-OPDA-Ile levels varied widely, raising questions concerning its role in Arabidopsis stress responses.

A ruthenium(II) complex with the propionate ion: Synthesis, characterization and cytotoxic activity

The complex [Ru(η 2 -O 2 CCH 2 CH 3 )(dppe) 2 ]PF 6 (dppe = 1,2-bis(diphenylphosphino)ethane) was prepared and characterized by elemental analysis, spectroscopic techniques, X-ray crystallography, HRESIMS and HRESIMS/MS. The characterization data are consistent with a cis arrangement for the dppe ligands and a bidentate coordination of the propionate ligand through carboxylate oxygens. Cytotoxicity assays were carried out on human and murine cancer and normal cell lines. In general, the [Ru(η 2 -O 2 CCH 2 CH 3 )(dppe) 2 ]PF 6 complex was more cytotoxic than both its precursor cis –[RuCl 2 (dppe) 2 ] and the reference metallodrug cisplatin. The best results against the HepG2 human tumour cell line and S180 murine tumour cell line were found with IC 50 values of 6.5 ± 0.2 and 0.18 ± 0.03 μM, respectively.

New Cationic and Neutral Ru(II)- and Os(II)-dmso carbonyl Compounds

The preparation and structural characterization of three cationic Ru(II)-dmso carbonyls and of four neutral mono- and dicarbonyl Os(II)-dmso derivatives is reported. The two monocarbonyl species fac-[Ru(CO)(dmso-O)3(dmso-S)2][PF6]2 (11) and cis,cis,cis-[RuCl(CO)(dmso-O)2(dmso-S)2][PF6] (12) were obtained from the neutral monocarbonyl precursor cis,trans,cis-[RuCl2(CO)(dmso-O)(dmso-S)2] (3) upon stepwise replacement of the chlorides with dmso, that binds in each case through the oxygen atom. The dicarbonyl cationic complex cis,cis,trans-[Ru(CO)2(dmso-O)2(dmso-S)Cl][PF6] (13) was instead obtained upon treatment of the neutral tricarbonyl precursor fac-[RuCl2(CO)3(dmso-O)] (8) with AgPF6 in the presence of DMSO: replacement of a Cl(-) with a dmso-O implied also the substitution of one CO ligand by another dmso (that binds through S trans to Cl). The Os(II) carbonyls trans,trans,trans-[OsCl2(CO)(dmso-O)(dmso-S)2] (17), trans,cis,cis-[OsCl2(CO)2(dmso-O)2] (18), cis,mer-[OsCl2(CO)(dmso-S)3] (19), and cis,trans,cis-[OsCl2(CO)(dmso-O)(dmso-S)2] (20) were obtained by treatment of the Os(II)-dmso precursors trans-[OsCl2(dmso-S)4] (14) and cis,fac-[OsCl2(dmso-O)(dmso-S)3] (15) with CO. Each one of them is structurally similar to an already known Ru(II) analog, even though--in agreement with the expected greater inertness of Os(II)--more forcing reaction conditions were required for their preparation. Interestingly, compound 20 could not be isolated in pure form, but only as a 1:1 cocrystallized mixture with its precursor 15. The dmso ligand is always bound through the oxygen atom when trans to CO. We are confident that the new Ru(II)- and Os(II)-dmso carbonyl species described here represent a contribution to expand the pool of complexes bearing some easily replaceable dmso ligands to be used as well-behaved precursors in inorganic synthesis.