Complexes 2a Research Articles

Photodegradation of rhodamine-B and methyl orange employing nano-alumina developed from new aluminium(III) complex(es) associated with phenanthridine-salicylaldehyde derived ligands

A series of five new heteroleptic mononuclear derivatives of aluminium(III) have been synthesized and characterized. Complexes [(CH3COCH2COCH3)2Al(1a)] 2a, [(CH3COCH2COCH3)2Al(1b)] 2b, [(CH3COCH2COCH3)2Al(1c)] 2c, [(CH3COCH2COCH3)2Al(1d)] 2d and [(CH3COCH2COCH3)2Al(1e)] 2e were obtained by treating Al(OPr i )3 with acetylacetone and bidentate ligands (developed by treating phenanthridine and salicylaldehyde) 1a–1e (1a = C27H21NO; 1b = C28H23NO2; 1c = C34H33NO4; 1d = C27H20BrNO; 1e = C27H20N2O3) in 1:2:1 stoichiometry using anhydrous benzene as solvent. All the newly synthesized aluminium(III) complexes were characterized by NMR (1H and 13C), FTIR, HPLC, HRMS and elemental analysis. Derivatives 2a-2e were confirmed by dept-135 and HSQC also. Complex 2a was employed as precursor for the synthesis of active alumina by well-established sol-gel technique. Nanostructured alumina was confirmed by powder XRD, FTIR, TGA-DTA and BET surface area, Fe-SEM and TEM analyses. Alumina synthesized from 2a was used for photodegradation of rhodamine-B and methyl orange dyes that resulted in remarkably high (>93%) decolorization within 140 minutes exposure of natural sunlight.

The catalytic activity difference of bis(phosphinite) pincer ligated Pt(II) thiolate and hydride complexes against hydrosilylation of aldimines

• POCOP pincer Pt thiolate and hydride complexes are good catalysts for hydrosilylation of aldimines • The thiolate complexes are more active than the hydride complexes • The reactions feature with good functional group compatibility and wide substrate scope • The expected amine products can be isolated in good to excellent yields In order to get information about the catalytic activities of bis(phosphinite) (POCOP) pincer ligated group 10 metal thiolate and hydride complexes against the hydrosilylation of unsaturated carbon-heteroatom bonds, platinum(II) complexes [2,6-( t Bu 2 PO) 2 C 6 H 3 ]PtX (X = SH, 1a; SPh, 1b; H, 1c) and [2,6-( i Pr 2 PO) 2 C 6 H 3 ]PtH (2) were applied to the catalytic hydrosilylation of aldimines. It was found that both auxiliary ligand and donor substituent play very important roles in affecting the catalytic activity of the platinum center. The hydride complex 1c is almost inactive in catalyzing the reactions; however, the hydride complex 2, which processes less bulky donor substituents ( i Pr vs t Bu), is an active catalyst. Meanwhile, the thiolate complexes 1a and 1b, which have the same donor substituents as 1c, are active catalysts and 1a is among most effective catalysts for this type of reaction. The catalytic reactions are featured with a wide substrate scope with relatively high turnover frequencies. Both aromatic and aliphatic aldimines were successfully hydrosilylated and the expected amines were isolated in good to excellent yields after basic hydrolysis of the hydrosilylation products. Functional groups such as OMe, halogens and internal C=C double bond were unaffected during the reactions. Although the hydride complex 2 is an active catalyst, it is less effective than the thiolate complex 1a despite the fact that the metal center in 2 is less sterically hindered by the donor substituents. As a result, the thiolate complexes are more active than the hydride complexes in catalyzing the reactions. The possible reasons for the different catalytic activities of these complexes are discussed.

Pd-NHC complex catalyzed C-H bond activation reactions of caffeine and 2-isobuthylthiazole

A series of new Pd-NHC complexes were synthesized, characterized, and utilized as catalysts on 8-(hetero)arylation of xanthines and C-5 (hetero)arylation of 2-isobuthylthiazole. All the synthesized derivatives were characterized by NMR, Q-TOF-LC/MS, FTIR, and X-ray (for 4a, 5a, and 5b) analysis. In addition, DFT calculations and computational NBO studies for Pd-NHC complexes were examined, and HOMO and LUMO energy levels and electron density of each Pd-NHC complex were defined. 4a-c and 5a-b complexes showed good catalytic activity in C-H bond activation reactions. DFT studies have also been conducted to examine the reaction mechanism following the CMD pathway. Complex 5a was chosen as a representative catalyst for the reaction of unsubstituted phenyl with caffeine and 2-isobuthylthiazole. Although the ΔE values of the complexes are so close, slight difference in the catalytic activity were observed for 4a-c and 5a-b. Since this low ΔE value facilitates the oxidative addition reaction of (hetero)aryl bromides, thanks to this catalytic system, new 8-(hetero)aryl xanthines and 5-(hetero)aryl thiazole derivatives could be synthesized with high yields and low catalyst loading.

Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication

Zinc pyrithione (1a), together with its analogues 1b–h and ruthenium pyrithione complex 2a, were synthesised and evaluated for the stability in biologically relevant media and anti-SARS-CoV-2 activity. Zinc pyrithione revealed potent in vitro inhibition of cathepsin L (IC50=1.88 ± 0.49 µM) and PLPro (IC50=0.50 ± 0.07 µM), enzymes involved in SARS-CoV-2 entry and replication, respectively, as well as antiviral entry and replication properties in an ex vivo system derived from primary human lung tissue. Zinc complexes 1b–h expressed comparable in vitro inhibition. On the contrary, ruthenium complex 2a and the ligand pyrithione a itself expressed poor inhibition in mentioned assays, indicating the importance of the selection of metal core and structure of metal complex for antiviral activity. Safe, effective, and preferably oral at-home therapeutics for COVID-19 are needed and as such zinc pyrithione, which is also commercially available, could be considered as a potential therapeutic agent against SARS-CoV-2.

Synthesis, structural characterization and catalytic application of zinc and cadmium sulfur complexes with imidazol-2-ylidene-N’-phenylthiourea ligand scaffold

We report the synthetic and structural studies of a series of zinc metal complexes, [(ImRNCSN(H)Ph)2ZnX2] (R = Mesityl (Mes), X = Cl (1a), Br (1b), I (1c); R = 2,6-Diisopropylphenyl (Dipp), X = Cl (2a), Br (2b), I (2c)) and the cadmium metal complexes [(ImRNCSN(H)Ph)2CdX2] (R = Mes, X = Cl (3a), I (3b)] and [(ImRNCSN(H)Ph)CdX]2 [R = Dipp, X = Cl (4a), I (4b)). The solid-state structures of metal complexes 1c, 2c, 3a, 4a, and 4b were established by single-crystal X-ray diffraction analysis. The zinc complexes 1c, 2c, and cadmium complex 3a are isostructural in solid-state, and in each case, the metal ion is ligated with two ligand moieties in a monodentate fashion via the sulfur atom. Despite similar coordination features, they exhibited a marked variation in the orientation of phenylthiourea scaffold as well as hydrogen-bonding interactions. The solid-state structures of cadmium complexes 4a and 4b involve a centrosymmetric dimer containing four-membered ring –[Cd-X−]2, formed by μ2-coordination of the halide group on each cadmium atom. In all the complexes, the metal ion (Zn2+/Cd2+) adopts a distorted tetrahedral MS2X2 environment. Additionally, the catalytic activity of [(ImMesNCSN(H)Ph)2ZnI2] (1c) as an active pre-catalyst is reported in the NH addition of amines to readily available carbodiimides to produce a series of substituted guanidine derivatives in an excellent yield. The zinc complex 1c showed very good conversion and tolerance of a broad and valuable substrate scope during the guanidine formation.

Synthesis and biological evaluation of Au‐NHC complexes

New seven Au‐N‐heterocyclic carbene (NHC) complexes have been synthesized via transmetalation from Ag‐NHC complexes. NHC salts, Ag‐NHC, and Au‐NHC complexes were fully characterized by widely used spectroscopic techniques. The molecular and crystal structures of3band3fAu‐NHC complexes were clarified through the single‐crystal X‐ray diffraction method. According to X‐ray diffraction analysis results, the coordination geometry around Au(I) atoms in the complexes are revealed to be almost linear with C–Au–Cl angle. Anticancer activity, DNA binding, xanthine oxidase (XO) inhibitory activity studies, and molecular docking studies were evaluated for all Au‐NHC complexes to explore the binding mechanism at the active site. The IC50value of Au‐NHC complexes against human colorectal cancer (Caco‐2) and breast cancer (MCF‐7) cell lines was defined by MTT assay. The IC50values for MCF‐7 in the range of 5.2 ± 2 to 152.4 ± 1 μM and Caco‐2 5.2 ± 1 to 152.7 ± 2 μM showed that3a,3b,3c,3d, and3ghave better anticancer activity than Cisplatin incredibly complex3aagainst both cancer cell line. All Au‐NHC complexes showed excellent antimicrobial activity against different bacteria and fungi.3awas the complex that exhibited the best antimicrobial activity here as well. The XO inhibitory activity experimental results indicated that all gold complexes showed remarkable inhibition activity against XO compared to the generally used standard, allopurinol. The range of IC50value was determined from 0.407 to 2.681 μM.3dcomplex showed the lowest IC50 value at 0.407 μM. DNA binding experiments were performed using agarose gel electrophoresis to observe the ability of synthesized Au‐NHC complexes to interact with the supercoiled pUC19 plasmid DNA. Molecular docking studies were performed to determine the binding mode of all active compounds against the XO enzyme, antibacterial, antifungal, and MCF‐7 cell lines.

Physical–chemical studies of new, versatile carbazole derivatives and zinc complexes: Their synthesis, investigation of in vitro inhibitory effects on α‐glucosidase and human erythrocyte carbonic anhydrase I and II isoenzymes

In this study, two novel zinc–phthalocyanine complexes (4a and 6a), containing carbazole rings, were investigated. The first phthalocyanine 4a has been synthesized from 4‐(2‐(3‐acetyl‐9H‐carbazol‐9‐yl)ethoxy at the peripheral position. Likewise, the second phthalocyanine 6a has been synthesized from 4‐(2‐(3‐cinnamoyl‐9H‐carbazol‐9‐yl)ethoxy at the same position. The new phthalocyanines (Pcs) and their ligands are soluble in organic solvents, such as dimethylformamide, dimethyl sulfoxide, dichloromethane, ethyl acetate, and methanol/ethanol. The Zn (II) complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR) (except 13C NMR for complexes), elemental analysis, mass spectrometry, and UV–Vis spectroscopy. Also, photophysical and photochemical properties and cyclic voltammogram for the N‐substituted carbazole zinc–Pcs have been reported. The evaluation of carbazole Zn (II) complexes (4a and 6a) and ligands (3, 4, 5, and 6) for in vitro α‐glucosidase inhibitory activities was performed compared to standard drugs acarbose, and kinetic studies were also carried out to determine their inhibition modes. The inhibitory effects of these new Pcs (4a and 6a) and their ligands (3, 4, 5, and 6) on human erythrocytes carbonic anhydrase I (hCA I) and II (hCA II) isoenzymes were investigated. Moreover, in silico studies were also carried out to better investigate the interactions of N‐substituted carbazole containing zinc Pcs with the active sites of hCA I and II isoforms.

Chirality influence on the cytotoxic properties of anionic chiral bis(N-heterocyclic carbene)silver complexes

Complexes Na3[Ag(NHCR)2], 2a-e and 2b’-c’, where NHCR is a N-heterocyclic carbene of the 2,2′-(1H-2λ3,3λ4-imidazole-1,3-diyl)dicarboxylate type, were prepared by treatment of compounds HLR, 1a-e and 1b’-c’ (2-(1-(carboxyalkyl)-1H-imidazol-3-ium-3-yl)carboxylate), with silver oxide in the presence of aqueous sodium hydroxide. They were characterized by analytical, spectroscopic (infrared, IR, 1H and 13C nuclear magnetic resonance, NMR, and circular dichroism) and X-ray methods (2a). In the solid state, the anionic part of complex 2a, [Ag(NHCH)2]3−, shows a linear disposition of Ccarbene-Ag-Ccarbene atoms and an eclipsed conformation of the two NHC ligands. The proposed bis(NHC) nature of the silver complexes was maintained in solution according to NMR and density functional theory (DFT) calculations. The cytotoxic activity of compounds 2 was evaluated against four cancer cell lines and one non-cancerous cell line and several structure-activity correlations were found for these complexes. For instance, the activity decreased when the bulkiness of the R alkyl group in Na3[Ag(NHCR)2] increased. More interesting is the detected chirality-anticancer relationship, where complexes Na3[Ag{(S,S)-NHCR}2] (R = Me, 2b; iPr, 2c) showed better anticancer activity than those of their enantiomeric derivatives Na3[Ag{(R,R)-NHCR}2] (R = Me, 2b’; iPr, 2c’).

Ruthenium indenylidene complexes bearing bis(N-Alkyl/N’-Mesityl)-sided heterocyclic carbene ligands

We report on the synthesis and characterization of new ruthenium indenylidene complexes bearing two unsymmetrical N-heterocyclic carbene (NHC) ligands denoted as RuCl2(3-phenyl-1-indenylidene)bis(1-mesityl-3-R-4,5-dihydroimidazole-2-ylidene) in which R is methyl 7a and cyclohexyl 7b. Complexes 7a and 7b were analyzed using single-crystal X-ray diffraction analysis, elemental analysis, IR, NMR spectroscopy, and HRMS. The catalytic activities of complexes 7a and 7b were evaluated in olefin metathesis reactions: ring-opening metathesis polymerization (ROMP) of cis,cis-1,5-cyclooctadiene (COD) and ringclosing metathesis (RCM) of diethyl diallyl malonate (DEDAM) as well as in the isomerization of allylic alcohols. Complexes 7a and 7b failed to initiate the reactions at room temperature in all tested reactions, which might be due to the high thermal stability and low degree of lability of the Ru-CNHC bonds. At 80 °C, the complex 7a showed the best performance due to an increased initiation and a decreased steric obstruction towards the incoming substrates.

N-heterocyclic carbene platinum-butadiyne Click/iClick complexes. Towards blue-violet phosphorescence

By employing two different methods, namely, Click and iClick, a series of four trans-NHC-Pt(II) triazole-acetylide complexes containing benzyl (3a), methylnaphthalene (3b), methylanthracene (3c), and phenyl (3d) substituents at the terminal triazole ring were synthesized and characterized. The traditional click approach involves first synthesizing a triazole-acetylene and then attaching to the Pt ion. In the iClick approach, the triazole is formed via cycloaddition by combining a trans-platinum butadiyne with the corresponding organic azide. The complexes were interrogated to determine the effects of conjugation and ligand substituent on their photophysical properties. Complex 3a exhibits a photoluminescence lifetime of 4.3 μs at 77 K. Ascribed to emission from conformers differing due to the torsion of the aryl acetylide ligands, employing different excitation wavelengths results in different emission spectra. Complex 3a emits in the violet region with CIE coordinates of (0.159, 0.021) under 290 nm excitation and shifts to CIE coordinates of (0.161, 0.019) under 320 nm excitation. Complex 3d, having a photoluminescence lifetime of 13.1 μs at room temperature, emits in the sky-blue region with CIE coordinates of (0.237, 0.355).

Supramolecular chemistry of organoplatinum(IV) complexes: A syndiotactic polymer with uracil substituents

The reaction of RCH2X with [PtMe2(DPA)], 1, (DPA = di-2-pyridylamine) has given [PtXMe2(CH2R)(DPA)] by cis oxidative addition to give 2a, when R = 6-uracil, X = Cl, or 3a, when R = CO2H, X = Br, but by a mixture of cis and trans oxidative addition to give 4a/4b when R = 4-C6H4CO2H, X = Br. The unusual cis stereochemistry of oxidative addition is rationalized thermodynamically by the formation of an intramolecular hydrogen bond in 2a and 3a but not 4a, and kinetically by the role of the ligand DPA NH group in hydrogen bonding to halide. Complex 2a in the solid state forms an unusual supramolecular syndiotactic polymer by forming two different intermolecular NH..O=C hydrogen bonds to neighbouring molecules.

Mononuclear Tricoordinate Copper(I) and Silver(I) Halide Complexes of a Sterically Bulky Thiourea Ligand and a Computational Insight of Their Interaction with Human Insulin.

Reaction of two equivalents of the bulky 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with MX (being M = Cu+, Ag+; and X = Cl−, Br−, I−) in acetonitrile afforded neutral complexes of the type [MXL2] [CuClL2].2CH3CN (1a); [CuBrL2].2CH3CN (1b); [CuIL2] (1c): [AgClL2] (2a); [AgBrL2] (2b) and [AgIL2] (2c). The two aromatic groups in free ligand were found to be trans with respect to the thiourea unit, which was a reason to link the ligand molecules via intermolecular hydrogen bonding. Intramolecular hydrogen bonding was observed in all metal complexes. The copper complexes 1a and 1b are acetonitrile solvated and show not only intra- but also intermolecular hydrogen bonding between the coordinated thiourea and the solvated acetonitrile molecules. Silver complexes reported here are the first examples of structurally characterized tricoordinated thiourea-stabilized monomeric silver(I) halides. Molecular docking studies were carried out to analyze the binding modes of the metal complexes inside the active site of the human insulin (HI) protein. Analysis of the docked conformations revealed that the electrostatic and aromatic interactions of the protein N-terminal residues (i.e., Phe and His) may assist in anchoring and stabilizing the metal complexes inside the active site. According to the results of docking studies, the silver complexes exhibited the strongest inhibitory capability against the HI protein, which possesses a deactivating group, directly bonded to silver. All compounds were fully characterized by elemental analysis, NMR spectroscopy, and molecular structures of the ligand, and five out of six metal complexes were also confirmed by single-crystal X-ray diffraction.

Formation of Iridium(III) and Rhodium(III) Amine, Imine, and Amido Complexes Based on Pyridine-Amine Ligands: Structural Diversity Arising from Reaction Conditions, Substituent Variation, and Metal Centers.

Herein, we present the different coordination modes of half-sandwich iridium(III) and rhodium(III) complexes based on pyridine-amine ligands. The pyridyl-amine iridium(III) and rhodium(III) complexes, the corresponding oxidation pyridyl-imine products, and 16-electron pyridyl-amido complexes can be obtained through the change in reaction conditions (nitrogen/adventitious oxygen atmosphere, reaction time, and solvents) and structural variations in the metal and ligand. Overall, the reaction of pyridine-amine ligands with [(η5-C5(CH3)5)MCl2]2 (M = Ir or Rh) in the presence of adventitious oxygen afforded the oxidized pyridyl-imine complexes. The possible mechanism for the oxidation of iridium(III) and rhodium(III) amine complexes was confirmed by the detection of the byproduct hydrogen peroxide. Moreover, the formation of pyridyl-amine complexes was favored when nonpolar solvent CH2Cl2 was used instead of CH3OH. The rarely reported complex with [(η5-Cp*)IrCl3] anions can also be obtained without the addition of NH4PF6. The introduction of the sterically bulky i-Bu group on the bridge carbon of the ligand led to the formation of stable 16-electron pyridyl-amido complexes. The pyridyl-amine iridium(III) and rhodium(III) complexes were also synthesized under a N2 atmosphere, and no H2O2 was detected in the whole process. In particular, the aqueous solution stability and in vitro cytotoxicity toward A549 and HeLa human cancer cells of these complexes were also evaluated. No obvious selectivity was observed for cancer cells versus normal cells with these complexes. Notably, the represented complex 5a can promote an increase in the reactive oxygen species level and induce cell death via apoptosis.

Copper(II) complexes supported by 8-hydroxyquinoline-imine ligands: Synthesis, characterization and catalysis in aerobic alcohols oxidation

Treatment of Cu(OAc)2·4H2O with 8-hydroxylquinoline-imine ligands [2-(ArN = HC)-8-OH]C9H5N (Ar = 2,6-iPr2C6H3, L1H; Ar = 4-ClC6H4, L2H; Ar = 4-BrC6H4, L3H and Ar = 4-OMeC6H4, L4H) in refluxing EtOH gave the dual-ligand coordinated copper complexes [L2Cu] 1a-1d in good yields, respectively. All the four Cu complexes were characterized by IR, EPR, elemental analysis and HR-MS. Furthermore, the molecular structures of complexes 1a and 1d were further confirmed by X-ray crystallographic analysis. These complexes displayed high catalytic activity and good selectivity for aerobic oxidation of primary and secondary alcohols in the presence of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl) as the co-catalyst. The yields of desired aldehydes are decent (up to 84%) and the corresponding yields of ketones are in the range of 78–91%.

Coordination Polymerization of Renewable (E)‐4,8‐Dimethyl‐1,3,7‐Nonatriene by Rare‐Earth Metal Catalysts

Comprehensive SummaryCoordination polymerization of renewable (E)‐4,8‐dimethyl‐1,3,7‐nonatriene (DMNT) has been performed using pyridyl‐methylene‐ fluorenyl scandium complex 1, half‐sandwich scandium complex 2, diiminophosphinato rare‐earth metal complexes 3a—3c and 4a—4b, bis(phosphino)carbazolide yttrium complex 5 and β‐diketiminato yttrium complex 6. Fluorenyl scandium complexes 1 and 2, activated by [Ph3C][B(C6F5)4] and AliBu3, are moderately active and show perfect 1,2‐regioselective (1,2 > 99%). Conversely, asymmetric diiminophophinato complexes 3a—3c promote the DMNT polymerization to produce high trans‐1,4 regulated products with the activity trend: Sc < Lu < Y. Complexes 4—6 are virtually inactive for the DMNT polymerization although they are highly active in isoprene polymerization. A diblock copolymer bearing 3,4‐polyisoprene block and trans‐1,4‐poly(DMNT) block is obtained using complex 3c in one‐pot reaction. Hydrogenation of trans‐1,4‐poly(DMNT) affords an elastomer with a Tg of –10°C. The epoxidation reaction of trans‐1,4‐poly(DMNT) with 3‐chloroperbenzoic acid transfers the pendant double bonds in the cis configuration into the epoxy groups.

Enhancing quantum efficiency in Pt-based emitters using a pendant closo-monocarborane cluster to enforce charge neutrality

The use of organometallic triplet emitters in OLED applications may be complicated when the luminescent complex bears a formal charge. By designing ligands containing pendant closo-monocarborane clusters [CB11H11]−, it is possible to neutralize the otherwise cationic cores of cyclometalated Pt(II) complexes bearing bis-carbenes, resulting in significantly enhanced photophysical properties. Herein, we report four Pt(II) complexes decorated with a monoanionic closo-monocarborane by coupling the cluster to the classic cyclometallating moiety, phenylpyridine (ppy). All four complexes were fully characterized by NMR, HR-MS, UV–Vis, and cyclic voltammetry. Complexes 1b, 1c and 2a were characterized by single-crystal X-ray diffraction. Moreover, all four complexes show interesting photophysical behaviors, with complex 1a exhibiting a photoluminescent quantum yield of 97% in a 2 wt% PMMA film. This high efficiency prompted the incorporation of 1a and 1c into an OLED device using solution processing, resulting in green emission with CIE coordinates of (0.28, 0.55) for 1a and yellow emission with CIE coordinates of (0.44, 0.50) for 1c. The measured maximum external quantum efficiency (EQEmax) was 18.51% for 1a, an EQEmax that is among the highest for solution-processed OLED devices containing Pt(II) complexes with simple cyclometalated ppy ligands.

Biotin-Targeted Au(I) Radiosensitizer for Cancer Synergistic Therapy by Intervening with Redox Homeostasis and Inducing Ferroptosis.

The search for highly selective sensitizers with a novel mechanism for tumor targeting therapy is of considerable interest. In this work, we have developed a series of new biotin-targeted Au(I) complexes. Through systematic biological evaluation and comparison, biotinylated Au(I) complex 3a containing a triphenylphosphine ligand was screened, as it realized both prominent efficient inhibition and selective cytotoxicity to cancer cells, and the effect was better than that of popularly used auranofin. Meanwhile, complex 3a, as a potent radiosensitizer, enhances anticancer effects in vitro and in vivo and has sensitization selectivity. From the action mechanism study, we provide evidence that complex 3a could intervene in redox homeostasis through targeted binding and strong suppression of thioredoxin reductase (TrxR) and induce the ferroptosis death process, enabling it to sensitize tumor cells to radiotherapy. Thus, complex 3a has enormous potential as an efficient and specific radiosensitizing agent in cancer therapy.

Target Profiling of an Iridium(III)-Based Immunogenic Cell Death Inducer Unveils the Engagement of Unfolded Protein Response Regulator BiP.

Clinical chemotherapeutic drugs have occasionally been observed to induce antitumor immune responses beyond the direct cytotoxicity. Such effects are coined as immunogenic cell death (ICD), representing a "second hit" from the host immune system to tumor cells. Although chemo-immunotherapy is highly promising, ICD inducers remain sparse with vague drug-target mechanisms. Here, we report an endoplasmic reticulum stress-inducing cyclometalated Ir(III)-bisNHC complex (1a) as a new ICD inducer, and based on this compound, a clickable photoaffinity probe was designed for target identification, which unveiled the engagement of the master regulator protein BiP (binding immunoglobulin protein)/GRP78 of the unfolded protein response pathway. This has been confirmed by a series of cellular and biochemical studies including fluorescence microscopy, cellular thermal shift assay, enzymatic assays, and so forth, showing the capability of 1a for BiP destabilization. Notably, besides 1a, the previously reported ICD inducers including KP1339, mitoxantrone, and oxaliplatin were also found to engage BiP interaction, suggesting the important role of BiP in eliciting anticancer immunity. We believe that the ICD-related target information in this work will help to understand the mode of action of ICD that is beneficial to designing new ICD agents with high specificity and improved efficacy.

Phosphorus-nitrogen compounds: Part 61. The novel sodium complexes of monoferrocenylspirocyclotriphosphaza-crown ethers

In the present investigation, it is observed that condensation reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (HCCP, trimer) and four different diamines (1–4) yielded tetrachloromono (5, 7 and 8) and bisferrocenyl (6) spirocyclotriphosphazenes. Reactions of 5, 7 and 8 with two equimolar amounts of 1-aza-15-crown-5 ether (L) produced new monoferrocenylspirocyclotriphosphazabis(crown ethers) (9, 10 and 12) in THF, respectively. The only monoferrocenylspirocyclotriphosphazatris(crown ether) (13) was obtained from the reaction of 8 with three equimolar amounts of L. However, reactions of 7 and 8 with four equimolar amounts of L resulted in the formation of monoferrocenylspirocyclotriphosphaza-tetrakis(crown ethers) 11 and 14. In addition, the complexation reactions of ditopic phosphaza-crown ethers (9, 10 and 11) with NaClO4 yielded novel mononuclear sandwich-type sodium complexes (9a, 10a and 11a). Tri- and tetranuclear complexes (13a and 14a) were obtained as a result of the complexation reactions of tri- and tetratopic phosphaza-crown ethers (13 and 14) with NaClO4. Characterizations of phosphaza-crown ethers and complexes were performed using elemental analysis, mass spectrometry, FTIR, and 1H, 13C and 31P NMR techniques. Ditopic phosphazenes (9, 10 and 12) and complexes (9a, 10a and 11a) have a stereogenic P center. While the tritopic ligand (13) and complex (13a) have two stereogenic P centers. They are expected to be in racemic mixtures. In addition, crystal structures of phosphazenes 6 and 9 were elucidated using X-ray crystallography. The absolute configurations of the enantiomers of 9 were determined as R and S. Furthermore, intermolecular interactions in crystal structures of 6 and 9 were determined by Hirshfeld surface (HS) analysis.

1,2σ3λ3-Oxaphosphetanes and Their P-Chalcogenides-A Combined Experimental and Theoretical Study.

Although 1,2σ5λ5-oxaphosphetanes have been known for a long time, the “low-coordinate” 1,2σ3λ3-oxaphosphetanes have only been known since their first synthesis in 2018 via decomplexation. Apart from ligation of this P-heterocycle to gold(I)chloride and the oxidation using ortho-chloranil, nothing on their chemistry has been reported so far. Herein, we describe the synthesis of new 1,2σ3λ3-oxaphosphetane complexes (3a–e) and free derivatives (4a–e), as well as reactions of 4a with chalcogens and/or chalcogen transfer reagents, which yielded the P-chalcogenides (14–16a; Ch = O, S, Se). We also report on the theoretical results of the reaction pathways of C-phenyl-substituted 1,2 σ3λ3-oxaphosphetanes and ring strain energies of 1,2σ4λ5-oxaphosphetane P-chalcogenides.