Effects of the ligand linkers on stability of mixed-valence Cu(I)Cu(II) and catalytic aerobic alcohol oxidation activity.

We synthesized a class of ligands that feature single (L1) and dual amine-bis(triazole) chelates (L2 with a 1,3-phenylene linker and L3 with a 1,5-naphthalene linker). Our findings which were derived from UV-Vis titrations, crystal structure analysis of relevant copper complexes, and DFT calculations indicate the formation of both mononuclear CuBr(L1) and dinuclear (µ-Ln)(CuBr)2 (Ln = L2 and L3) complexes. The catalytic activities of CuBr/Ln, in combination with TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) co-catalyst and NMI (N-methylimidazole) for aerobic alcohol oxidation, reveal the following activity trend: CuBr/L3 > CuBr/L2 > CuBr/L1. Furthermore, electrochemical data from in-situ generated CuBr complexes suggest that the higher catalytic performance of CuBr/L3 is attributed to the presence of less stable mixed-valence and more reducible Cu(I)-L3-Cu(II) species compared to Cu(I)-L2-Cu(II). This difference is a result of weaker σ interactions between Cu-Namine, larger bridging π systems, and a longer Cu···Cu distance in the presence of L3. Additionally, the catalyst system, CuBr/L3/TEMPO/NMI, efficiently promotes the aerobic oxidation of benzyl alcohol to benzaldehyde at room temperature in CH3CN with a high turnover frequency (TOF) of 38 h-1 at 1 h.

Ganopyrone A, a highly rearranged lanostane triterpenoid with antimalarial activity from artificially cultivated fruiting bodies of Ganoderma colossus.

Three previously undescribed highly modified lanostane triterpenoids, ganopyrone A, ganocolossusin I, and ganodermalactone Y, were isolated from the artificially cultivated fruiting bodies of the basidiomycete Ganoderma colossus TBRC-BCC 17711. Ganopyrone A possesses an unprecedented polycyclic carbon skeleton with an α-pyrone ring and C-18/C-23 bond. It showed antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain) with an IC50 value of 7.8 µM (positive control: dihydroartemisinin, IC50 1.4 nM), while its cytotoxicity (Vero cells) was much weaker (IC50 103 µM).

The role of organoaluminum and electron donors in propene insertion on the Ziegler-Natta catalyst.

Alkyl aluminium plays a primary role in activating Ti within Ziegler-Natta (ZN) catalysts for propylene polymerization. We performed density functional calculations to explore the additional roles of AlEt3 and AlEt2Cl, in conjunction with diisobutyl phthalate (DIBP) internal donor and dicyclopentyl dimethoxysilane (DCPDMS) external donor, to enhance the stereoselectivity of propene insertion. Based on our calculated adsorption energies on the (MgCl2)13/TiCl2iBu cluster model for the ZN catalyst, the presence of DIBP on the cluster essentially facilitated AlEt2Cl adsorption while AlEt2Cl also promoted the adsorption of DIBP. The reaction between AlEt3 and DIBP on the cluster led to the extraction of DIBP, creating an available site for DCPDMS adsorption. While the stereoselectivity, represented by the difference in the activation energies between 1,2-re and 1,2-si insertions of propene, was negligible on the cluster containing only DIBP, it became significant on the clusters containing both AlEt2Cl and DIBP (and DCPDMS). AlEt2Cl plays a pivotal role in imposing steric effects near the Ti active site, thereby increasing stereoselectivity. Our findings suggest the importance of including AlEt2Cl alongside DIBP (and DCPDMS) in the ZN cluster model to investigate stereoselective propene insertion. Considering AlEt2Cl adsorption and AlEt3 reaction with internal donors is essential in developing Ziegler-Natta catalysts.

Mechanisms of hydrogen evolution by six-coordinate cobalt complexes: a density functional study on the role of a redox-active pyridinyl-substituted diaminotriazine benzamidine ligand as a proton relay.

The hydrogen evolution reaction is an important process for energy storage. The six-coordinate cobalt complex [CoIII(L1-)(LH)]2+ (LH = N-(4-amino-6-(pyridin-2-yl)-1,3,5-triazin-2-yl)benzamidine) was found to catalyze photocatalytic hydrogen evolution. In this work, we performed density functional calculations to obtain the reduction potentials and the proton-transfer free energy of possible intermediates to determine the preferred pathways for proton reduction. The mechanism involves the metal-based reduction of Co(III) to Co(II) before the protonation at the amidinate N on the pyridinyl-substituted diaminotriazine benzamidinate ligand L1- to form [CoII(LH)(LH)]2+. Essentially, the subsequent electron transfer is not metal-based reduction, but rather ligand-based reduction to form [CoII(LH)(LH˙1-)]1+. Through a proton-coupled electron transfer process, the cobalt hydride [CoIIH(LH)(LH2˙)]1+ is formed as the key intermediate for hydrogen evolution. As the cobalt hydride complex is coordinatively saturated, a structural change is required when the hydride on Co is coupled with the proton on pyridine. Notably, the redox-active nature of the ligand results in the low acidity of the protonated pyridine moiety of LH2˙, which impedes its function as a proton relay. Our findings suggest that separating the proton relay fragment from the electron reservoir fragment of the redox-active ligand is preferred for fully utilizing both features in catalytic H2 evolution.

A highly sensitive and selective rhodamine-semicarbazide based fluorescent sensor for Cu2+ detection in real water samples and fluorescence bioimaging in HepG2 cells.

A colorimetric and fluorescent sensor, selective for Cu2+ ions, was synthesized in two steps using a rhodamine-based compound attached to the semicarbazide-picolylamine moiety (RBP). Spectroscopic measurements, including UV-Vis absorption and fluorescence emission, were conducted in the semi-aqueous medium containing acetonitrile/4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, denoted as MeCN/HEPES buffer (2:8, v/v, pH 7.0). The sensor exhibited high selectivity towards Cu2+ ions compared to other cations and demonstrated remarkable sensitivity towards Cu2+ ions, with a limit of detection at the nanomolar level. The calculated transitions indicated a 1:1 stoichiometric binding of RBP to Cu2+ ions based on a 4-coordination mode involving additional chelation in the semi-aqueous medium. The sensing mechanism for the detection of Cu2+ ions was investigated using high-resolution mass spectroscopy. The sensor could be employed as a real-time chemosensor for monitoring Cu2+ ions. Furthermore, the sensor has the potential for utilization in the detection of Cu2+ ions in actual water samples with the high precision and accuracy, as indicated by the small relative standard derivation values. The 50th percentile cytotoxicity concentration of RBP was found to be 22.92 µM. Additionally, the fluorescence bioimaging capability of RBP was demonstrated for the detection of Cu2+ ions in human hepatocellular carcinoma (HepG2) cells.

Tunable Metal-Free Imidazole-Benzimidazole Electrocatalysts for Oxygen Reduction in Aqueous Solutions.

A series of metal-free imidazole-benzimidazole catalysts (ImBenz-H, ImBenz-NO2 , ImBenz-OCH3 ) for oxygen reduction reaction (ORR) were prepared. We demonstrate that the electrocatalytic O2 reduction by ImBenz-NO2 with the electron-withdrawing group showed high selectivity toward H2 O with the number of electrons transferred (n=3.7) in a neutral aqueous solution. The highest ORR selectivity toward H2 O2 was achieved using ImBenz-H (n=2.4) in an alkaline solution. Electrochemical studies of reaction kinetics disclosed that the highest turnover frequencies were obtained from ImBenz-H in both neutral and alkaline aqueous solutions. The results prove that the ORR selectivity is tunable by modulating the substituent of the ImBenz catalysts. Furthermore, DFT calculations suggested that the ORR mechanism of ImBenz-H involves the electron transfer from imidazole-benzimidazole to O2 resulting in the formation of H2 O2 which supports the redox active properties of the catalysts ImBenz.

Oudemansin and 9-methoxystrobilurin derivatives with antimalarial activity from cultures of the basidiomycete Favolaschia minutissima: assignments of the absolute configurations of the isoprene-derived units.

Five undescribed polyketide metabolites, oudemansins E (1), M (2), P (3), and Q (4), and 9-methoxystrobilurin I (5), were isolated from cultures of basidiomycete Favolaschia minutissima TBRC-BCC 19434. A γ-lactone derivative (6) of noroudemansin A (8), which was previously reported as a semisynthetic compound, was also isolated. The absolute configuration of the isoprene-derived moiety of the known cometabolite 9-methoxystrobilurin E (9) was determined to be 2'R,6'S by comparison of the experimental and calculated ECD data, which was correlated to the new derivative 1. These compounds exhibited antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain). A putative minor natural product, namely 9-methoxystrobilurin P (13), was prepared by semisynthesis, which exhibited significant antimalarial activity (IC50 0.086 µM).

Base-catalyzed diastereodivergent thia-Michael addition to chiral ß-trifluoromethyl-α,ß-unsaturated N-acylated oxazolidin-2-ones.

Base-catalyzed diastereodivergent thia-Michael addition of thiols to chiral ß-trifluoromethyl-α,ß-unsaturated N-acylated oxazolidin-2-ones is reported. By tuning the base-catalyst (i-Pr2NEt, DABCO, or P2-t-Bu), a range of chiral thia-Michael adducts was synthesized in good yields with high diastereoselectivities. A plausible mechanism was proposed on the basis of the experimental results. This work is complementary to the existing methods offering advantages, e.g., switchable diastereoselectivity using a readily synthesized chiral starting material, a cheap and readily available base catalyst, and a simple and practical operation, enabling synthetic application in organic synthesis.

Migration of Hydride, Methyl, and Chloride Ligands between Al and M in (PAlP)M Pincer Complexes (M = Rh or Ir).

Protolysis of AlMe3 or AlBui3 with 2-diisopropylphosphinopyrrole (1) yields molecules containing two flanking phosphines and a central Al-Me (2-Me), Al-iBu (2-iBu), or Al-H (2-H) unit. The reactions of 2-Me with [L2MCl]2 (L = cyclooctene or 1/2 1,5-cyclooctadiene and M = Rh or Ir) in the presence of pyridine produces PAlClP pincer complexes (3-Rh and 3-Ir) with Al-Cl and M-Me bonds. The analogous reaction of a mixture of 2-iBu and 2-H with [L2MCl]2 and pyridine resulted in the formation of analogous Rh-H (4-Rh) and Ir-H (4-Ir) complexes. Treatment of 3-Rh with NaBEt3H produced compound 5-Rh with an Al-Me and a Rh-H bond; the analogous reaction of 3-Ir did not result in a clean product. 4-Ir accepted an equivalent of H2 to produce 6-Ir with two terminal Ir-H bonds and one bridging Al-H-Ir moiety, whereas 4-Rh did not react with H2. The density functional theoretical treatment is in accord with this finding, highlights the likely mechanism for the H2 addition, and supports the bonding picture in 6-Ir arising from NMR and X-ray diffraction (XRD) observations. Spectroscopic data and XRD studies are consistent with distorted square-pyramidal structures (about Rh or Ir) for compounds 3-5, with an alane occupying the apical position. Complexes 3 and 4 possess some of the shortest known Rh-Al or Ir-Al distances.

Incorporation of Cation Affects the Redox Reactivity of Fe-NNN Complexes on C-H Oxidation.

Cations such as Lewis acids have been shown to enhance the catalytic activity of high-valent Fe-oxygen intermediates. Herein, we present a pyridine diamine ethylene glycol macrocycle, which can form Zn(II)- or Fe(III)-complex with the NNN site, while allowing redox-inactive cations to bind to the ethylene glycol moiety. The addition of alkali, alkali earth, and lanthanum ions resulted in positive shifts to the Fe(III/II) redox potential. Calculation of dissociation constants showed the tightest binding with a Ba2+ ion. Density functional theory calculations were used to elucidate the effects of redox inactive cations toward the electronic structures of Fe complexes. Although the Fe-NNN complexes, both in the absence and presence of cations, can catalyze C-H oxidation of 9,10-dihydroanthracene, to give anthracene [hydrogen atom transfer (HAT) product], anthrone, and anthraquinone [oxygen atom transfer (OAT) products], highest overall activity and OAT/HAT product ratios were obtained in the presence of dications, that is, Ba2+ and Mg2+, respectively.

Amino-coumarin-based colorimetric and fluorescent chemosensors capable of discriminating Co2+, Ni2+, and Cu2+ ions in solution and potential utilization as a paper-based device.

New chemosensors, L1-L3, based on the coumarin Schiff base scaffold with substituent modifications, have been designed and synthesized. The chemosensors L1-L3 exhibited the absorbance and fluorescence spectral changes that can discriminate Co2+, Ni2+, and Cu2+ ions. Sensor L1 demonstrated the ability to respond to Co2+, Ni2+, and Cu2+ ions. Remarkably, the slight modification of substituent on L2 has been observed to cause selective binding to Ni2+ and Cu2+ ions while L3 can specifically detect Cu2+ ions. The in-situ formation of metal and ligand complexes was determined by Job's plot analysis. The limit of detection and the sensing ability of all probes are estimated to be within the range of safe drinking water. Incorporation of the sensing compounds into a paper-based detection system using a laminated paper-based analytical device (LPAD) was demonstrated and found to be consistent to those obtained from the batchwise solution measurements.

Color-tunable emissive heptagon-embedded polycyclic aromatic dicarboximides.

Heptagon-embedded polycyclic aromatic dicarboximides were developed as new push-pull fluorescent dyes through palladium-catalysed [4+3] annulation followed by nucleophilic substitution. The introduction of a seven-membered ring in these push-pull systems can efficiently modulate the optical properties leading to an enhancement of the fluorescence quantum yields up to 0.93 with color tunable emission covering the visible-NIR spectrum.

QM/MM Molecular Modeling Reveals Mechanism Insights into Flavin Peroxide Formation in Bacterial Luciferase.

Bacterial luciferase (Lux) catalyzes oxidation of reduced flavin mononucleotide (FMN) and aldehyde to form oxidized FMN and carboxylic acid via molecular oxygen with concomitant light generation. The enzyme is useful for various detection applications in biomedical experiments. Upon reacting with oxygen, the reduced FMN generates C4a-peroxy-FMN (FMNH-C4a-OO-) as a reactive intermediate, which is required for light generation. However, the mechanism and control of FMNH-C4a-OO- formation are not clear. This work investigated the reaction of FMNH-C4a-OO- formation in Lux using QM/MM methods. The B3LYP/6-31G*/CHARMM27 calculations indicate that Lux controls the formation of FMNH-C4a-OO- via the conserved His44 residue. The steps in intermediate formation are found to be as follows: (i) H+ reacts with O2 to generate +OOH. (ii) +OOH attacks C4a of FMNH- to generate FMNH-C4a-OOH. (iii) H+ is transferred from FMNH-C4a-OOH to His44 to generate FMNH-C4a-OO- while His44 stabilizes FMNH-C4a-OO- by forming a hydrogen bond to an oxygen atom. This controlling key mechanism for driving the change from FMNH-C4a-OOH to the FMNH-C4a-OO- adduct is confirmed because FMNH-C4a-OO- is more stable than FMNH-C4a-OOH in the luciferase active site.

Hydroboration of carbonyls and imines by an iminophosphonamido tin(II) precatalyst.

A novel three-coordinated tin(II) chloride [Ph2P(NtBu)2]SnCl (1) supported by an N,N'-di-tert-butyliminophosphonamide having two phenyl groups on the phosphorus atom was synthesized by the reaction of the starting lithium iminophosphonamide [Ph2P(NtBu)2]Li with SnCl2·(dioxane) in toluene. The molecular structure of 1 was established by X-ray diffraction analysis. Tin(II) chloride 1 can act as an efficient precatalyst for the hydroboration of a wide variety of aldehydes, ketones, and imines at -10 °C. DFT calculations propose that hydroboration involves hydride transfer from the corresponding tin(II) hydride intermediate [Ph2P(NtBu)2]SnH (10) to the carbonyl substrates via four-membered transition states (TS-12), affording three-coordinated tin(II) alkoxide intermediates [Ph2P(NtBu)2]SnOR (13), followed by the stepwise reaction of 13 with HBpin (pin = pinacolate) to release the boronate esters and regenerate the tin(II) hydride 10. The stoichiometric reaction of the in site-generated 10 with benzophenone 2a at -10 °C led to the formation of 13. Moreover, 13 also stoichiometrically reacted with HBpin at -10 °C, forming the corresponding boronate ester 3a and 10 based on the 1H NMR spectrum of the reaction mixture.

Charge neutral halogen bonding tetradentate-iodotriazole macrocycles capable of anion recognition and sensing in highly competitive aqueous media.

A series of neutral tetradentate halogen bonding (XB) macrocycles, comprising of two bis-iodotriazole XB donors were synthesised in 60-70% yields via a stepwise CuAAC-mediated cyclisation strategy. Extensive 1H NMR anion titration experiments reveal halide binding affinities are critically dependent on the substitution pattern of the xylyl spacer unit. The meta-substituted macrocycle remarkably displays cooperative tetradentate XB-halide anion recognition in highly competitive 40% aqueous-organic D2O/acetone-d6 (40 : 60, v/v) solvent mixtures. Integration of para-xylyl and naphthyl spacer units generates extended macrocyclic cavities, capable of selective oxalate recognition. Furthermore, preliminary fluorescence exeperiments reveal dicarboxylate specific sensing can be achieved through monitoring of the naphthylene centred emission.

Understanding the reactivity of geminal P/B and P/Al frustrated Lewis pairs in CO2 addition and H2 activation.

Understanding CO2 addition and H2 activation by geminal P/Z (Z = B, Al) frustrated Lewis pairs (FLPs) is crucial for the development of transition metal-free catalysts for hydrogenation of unsaturated compounds and CO2 conversion. The distortion-interaction energy decomposition and natural bond orbital were used to gain insights into the reactivity of CO2 addition and H2 activation. Remarkably, the orbital interactions in the reactions of CO2 and H2 with geminal P/B FLPs are stronger than those in the reactions with more reactive geminal P/Al FLPs, which contain a stronger Lewis acid. The fact that geminal P/B FLPs react with a higher energy barrier than geminal P/Al FLPs is actually due to the unfavorable core repulsion contribution to the interaction energy and the higher distortion energy found for the geminal P/B FLPs. In addition, we revealed that although the interaction energy is higher for H2 activation, the distortion energy is significantly lower for CO2 addition. Thus, geminal P/Z FLPs are more reactive toward CO2 than toward H2. Overall, the reactivity and thermodynamic stability for the reactions of geminal P/Z FLPs with CO2 and H2 are not affected by the type of bridging carbon (sp3-C or sp2-C) but mainly influenced by the substituents on P and Z (B or Al). An insight into the thermodynamic stability of the H2 activation product is gained by quantifying the hydride affinity, the proton affinity, and the stability of the zwitterionic product relative to the prototypical Lewis acid-base pair, PtBu3/B(C6F5)3.

Boesenmaxane Diterpenoids from Boesenbergia maxwellii.

Three new diterpenoids, boesenmaxanes A-C (1-3), with an unprecedented core skeleton consisting of an unusual C-C bond between C-12 and an exo-cyclic methylene C-13, were isolated from the rhizome extracts of Boesenbergia maxwellii. The structures were elucidated by analysis of spectroscopic and X-ray diffraction data. Electronic circular dichroism spectra were used to determine the absolute configuration. All the isolates were evaluated for their cytotoxic effects, anti-HIV activity, and antimicrobial activity. Boesenmaxanes A and C (1 and 3) showed significant inhibitory activity in the syncytium reduction assay, with EC50 values of 55.2 and 27.5 µM, respectively.

Insights into the Regioselectivity of Hydroheteroarylation of Allylbenzene with Pyridine Catalyzed by Ni/AlMe3 with N-Heterocyclic Carbene: The Concerted Hydrogen Transfer Mechanism.

The hydroheteroarylation of allylbenzene with pyridine as catalyzed by Ni/AlMe3 and a N-heterocyclic carbene ligand has recently been established. Density functional calculations revealed that the common stepwise pathway, which involves the C-H oxidative addition of pyridine-AlMe3 before the migratory insertion of allylbenzene, is unlikely as the migratory insertion needs to overcome a prohibitively high energy barrier. In contrast, the ligand-to-ligand hydrogen transfer pathway is more favorable in which the hydrogen is transferred directly from the para-position of pyridine-AlMe3 to C2 of allylbenzene. Our distortion-interaction analysis and natural bond orbital analysis indicate that the interaction energy is strongly correlated with the extent of the charge transfer from the alkene (hydrogen acceptor) to the pyridine-AlMe3 (hydrogen donor), which dictates the selectivity of the H-transfer to the C2 position of allylbenzene. Then, the subsequent C-C reductive elimination of the regioselective linear product is facilitated by the steric hindrance of the IPr ligand. Understanding these key factors affecting the product regioselectivity is important to the development of catalysts for hydroheteroarylation of alkenes.

Resistance to the "last resort" antibiotic colistin: a single-zinc mechanism for phosphointermediate formation in MCR enzymes.

MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the "last-resort" antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono- rather than multinuclear member of the alkaline phosphatase superfamily.

Alkanethiol-Mediated Cyclization of o-Alkynylisocyanobenzenes: Synthesis of Bis-Thiolated Indole Derivatives.

Reactions of o-alkynylisocyanobenzenes with a variety of alkanethiols (Alk-SH) provide the corresponding bis-thiolated indole derivatives. The advantages of the reaction include metal-free, room-temperature, mild reaction conditions and broad functional group compatibility. The reaction proceeds via nucleophilic addition of an alkanethiol to an isonitrile moiety, 5-exo cyclization, followed by nucleophilic addition of an alkanethiol to a 3-alkylidene indole intermediate. Density functional calculations on the electronic structures and relative free energies of 5-exo and 6-endo cyclization pathways support that the 5-exo cyclization is preferable.