Cations 1a Research Articles

In-silico antibacterial activity of piperazinyl-based copper(II) metallo-organic pharmacophores

The piperazinyl-based Cu(II)-Schiff base complex {[Cu(HL1′)(N3)]2∙(ClO4)2·4H2O} (1) [HL1′ is the Zwitter ionic form of (E)-2-((2-piperazin-1-ylethylimino)methyl)phenol] was synthesized and characterized by spectroscopic and single crystal X-ray diffraction studies. The X-ray single crystal structure analysis shows that the asymmetric unit of 1 contains a four-coordinate discrete complex cation, [Cu(HL1′)(N3)]+ (1a), with a perchlorate anion and a lattice water molecule. Two square planar units of 1a are dimerized by weak Cu···N intermolecular interaction, forming [Cu(HL1′)(N3)]2 2+ (1′a). DFT and TD-DFT calculations of the monomeric cationic unit, [Cu(HL1′)(N3)]+ (1a) were performed. In-silico antibacterial activities of HL1 as well as monomeric and dimeric cationic units 1a and 1'a, respectively, were performed and study shows that 1a (EC50 0.30 μM) and 1′a (EC50 0.06 μM) may be treated as antibacterial drugs after in-vivo analysis and clinical testing.

Photodynamic inactivation of a RNA-virus model using water-soluble β-octa-Substituted pyridinium-pyrazolyl phthalocyanines

Among the various groups of microorganisms, viruses have generally a greater capacity for mutation, especially RNA viruses, as was demonstrated by SARS-CoV2 virus mutations. This high mutation rate promotes the development of their resistance to traditional antivirals and establishes the resistance behaviour in virus populations, decreasing their susceptibility to these drugs. In this context, the photodynamic treatment appears as a potentially effective method against microorganisms and, considering its mode of action is not likely to lead to the development of resistance. In this work, two newly zinc(II) phthalocyanines (ZnPcs) bearing pyridinium-pyrazolyl groups (2a and 3a) were synthesized, characterized, and applied in photodynamic inactivation (PDI) of bacteriophage Φ6 (or Phage Phi6) as a RNA-virus model. These quaternized dyes were applied at different concentrations (from 5.0 to 20 μM, and under white light irradiation in the irradiance range between 50 and 150 mW/cm2) to test their efficiency for possible clinical or environmental applications. The results showed that the new cationic ZnPcs 2a and 3a efficiently inactivate the RNA-virus model (bacteriophage Φ6), even at the lowest tested irradiance. These compounds are thus promising photosensitizers to be used in various contexts.

Wodegongjieite, ideally KCa3(Al7Si9)O32, a new sheet silicate isostructural with the feldspar polymorph kokchetavite, KAlSi3O8

AbstractWodegongjieite occurs in the Cr-11 chromitite orebody of the Luobusa ophiolite in the Kangjinla district, Tibet, China. It is found in two inclusions in corundum: (1) as a partial overgrowth (holotype) up to 1.5 μm thick around a spheroid 20 μm across of wenjiite (Ti10(Si,P,□)7), kangjinlaite (Ti11(Si,P)10), zhiqinite (TiSi2) and badengzhuite (TiP), and (2) as pools up to 0.25 μm wide filling interstices between wenjiite, jingsuiite (TiB2), osbornite–khamrabaevite (Ti[N,C]) and corundum. Energy dispersive analyses gave Al2O3 34.09, SiO2 49.11, K2O 2.56, CaO 11.71, SrO 2.53, total 100.0 wt.%, corresponding to K0.58Sr0.26Ca2.25Al7.20Si8.80O31.20, ideally KCa3(Al7Si9)O32, for Si + Al = 16 cations.Single-crystal studies were carried out with three-dimensional electron diffraction providing data for an ab initio structure solution in the hexagonal space group P6/mcc (#192) with a = 10.2(2) Å, c = 14.9(3) Å, V = 1340(50) Å3 and Z = 2. Density (calc.) = 2.694 g⋅cm–3. The refinement, which assumes complete Si–Al disorder, gives average T1–O and T2–O bond lengths both as 1.65 Å. It was not practical to use unconstrained refinement for the occupancies of the large cation sites 6f and 2a. The ab initio model shows clearly that the two cation sites have different sizes and coordination. Consequently, we imposed the condition (1) that all the K occupies the 2a site as the average K–O bond length of 3.07 Å is close to the average K–O bond lengths reported in kokchetavite and (2) that all the Ca occupies the 6f site as the average Ca–O bond length of 2.60 Å (2.36 Å and 2.84 Å for Ca–O1 and Ca–O3, respectively) is reasonable for Ca–O. Assuming that all K and all Ca are located at the 2a site and 6f site, respectively, Sr occupancies of these sites could be refined. Thermal parameters are positive and in a reasonable range. The structure is a sheet silicate isostructural with the K-feldspar polymorph kokchetavite, with two crystallographically distinct sites for K, but not with the topologically identical anorthite polymorph dmisteinbergite (CaAl2Si2O8) with only a single site for Ca. Substitution of K by Ca at the 6f site is associated with marked rotation of the Si,Al tetrahedra and a collapse of the structure to accommodate the smaller Ca ion.The spheroid of intermetallic phases is believed to have formed from the interaction of mantle-derived CH4 + H2 fluids with basaltic magmas at depths of ~30–100 km, resulting in precipitation of corundum that entrapped intermetallic melts. Associated immiscible silicate melt of granodioritic composition crystallised metastably to wodegongjieite instead of a mixture of anorthite and K-feldspar.

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

Novel cationic-chalcone phthalocyanines for photodynamic therapy eradication of S. aureus and E. coli bacterial biofilms and MCF-7 breast cancer

New tetrasubstituted zinc (II) and indium (III) phthalocyanines bearing dimethylamino chalcone group (complexes 3 and 4) as well as their quaternized analogs (3a and 4a) have been assessed for their photodynamic therapy (PDT) of cancer as well as photodynamic antimicrobial chemotherapy activities against biofilms and planktonic cultures of pathogenic bacteria of Staphylococcus aureus and Escherichia coli. Compared to the non-quaternized phthalocyanines 3 and 4, the cationic phthalocyanines 3a and 4a exhibit a higher photodynamic inactivation against the planktonic cells with log reduction values above 9 at a concentration of 1.25 µM. This was attributed to the positive charge which enhances cellular uptake. More interestingly, 3a and 4a show a higher photodynamic inactivation (less than 3% of S. aureus survived) on their biofilm counterparts thanks to their stronger affinity to these cells. 3a and 4a Pcs also exhibited interesting PDT activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. The obtained results in this work show that the positively charged phthalocyanines 3a and 4a are potential antibacterial photosensitizers that show some selectivity toward the Gram-positive and Gram-negative bacteria as well as MCF-7 breasts cancer cells.

The Antimicrobial Photoinactivation Effect on Escherichia coli through the Action of Inverted Cationic Porphyrin-Cyclodextrin Conjugates.

Photodynamic action has been used for diverse biomedical applications, such as treating a broad range of bacterial infections. Based on the combination of light, dioxygen, and photosensitizer (PS), the photodynamic inactivation (PDI) approach led to the formation of reactive oxygen species (ROS) and represented a non-invasive, non-toxic, repeatable procedure for pathogen photoinactivation. To this end, different tetrapyrrolic macrocycles, such as porphyrin (Por) dyes, have been used as PSs for PDI against microorganisms, mainly bacteria. Still, there is significant room for improvement, especially new PS molecules. Herein, unsymmetrical new pyridinone (3–5) and thiopyridyl Pors (7) were prepared with α-, β-, or γ-cyclodextrin (CD) units, following their quaternization to perform the corresponding free-base Pors (3a–5a and 7a), and were compared with the already-known Pors 6a and 8a, both bearing thiopyridinium and CD units. These water-soluble porphyrins were evaluated as PSs, and their photophysical and photochemical properties and photodynamic effects on E. coli were assessed. The presence of one CD unit and three positive charges on the Por structure (3a–5a and 7a) enhanced their aqueous solubility. The photoactivity of the cationic Pors 3a–5a and 6a–8a ensured their potential against the Gram-negative bacterium E. coli. Within each series of methoxypyridinium vs thiopyridinium dyes, the best PDI efficiency was achieved for 5a with a bacterial viability reduction of 3.5 log10 (50 mW cm−2, 60 min of light irradiation) and for 8a with a total bacterial viability reduction (>8 log10, 25 mW cm−2, 30 min of light irradiation). Here, the presence of the methoxypyridinium units is less effective against E. coli when compared with the thiopyridinium moieties. This study allows for the conclusion that the peripheral charge position, quaternized substituent type/CD unit, and affinity to the outer bacterial structures play an important role in the photoinactivation efficiency of E. coli, evidencing that these features should be further addressed in the pursuit for optimised PS for the antimicrobial PDI of pathogenic microorganisms.

NHC-CDI Betaine Adducts and Their Cationic Derivatives as Catalyst Precursors for Dichloromethane Valorization.

Zwitterionic adducts of N-heterocyclic carbene and carbodiimide (NHC-CDI) are an emerging class of organic compounds with promising properties for applications in various fields. Herein, we report the use of the ICyCDI(p-Tol) betaine adduct (1a) and its cationic derivatives 2a and 3a as catalyst precursors for the dichloromethane valorization via transformation into high added value products CH2Z2 (Z = OR, SR or NR2). This process implies selective chloride substitution of dichloromethane by a range of nucleophiles Na+Z– (preformed or generated in situ from HZ and an inorganic base) to yield formaldehyde-derived acetals, dithioacetals, or aminals with full selectivity. The reactions are conducted in a multigram-scale under very mild conditions, using dichloromethane both as a reagent and solvent, and very low catalyst loading (0.01 mol %). The CH2Z2 derivatives were isolated in quantitative yields after filtration and evaporation, which facilitates recycling the dichloromethane excess. Mechanistic studies for the synthesis of methylal CH2(OMe)2 rule out organocatalysis as being responsible for the CH2 transfer, and a phase-transfer catalysis mechanism is proposed instead. Furthermore, we observed that 1a and 2a react with NaOMe to form unusual isoureate ethers, which are the actual phase-transfer catalysts, with a strong preference for sodium over other alkali metal nucleophiles.

Phenol-based styrylpyrylium dyes for trace water detection via chromogenic and fluorogenic responses

Two new styrylpyrylium cations (1a,b) have been synthesized in only two steps with high yields. The presence of an ortho-nitrophenol moiety in their structures makes them very sensitive to deprotonation by traces of water in organic solvents. The presence of humidity in solutions of those dyes in acetone, acetonitrile and THF leads to the formation of a new band at a long wavelength (ca. 600–800 nm) resulting from the formation of a quinoidal structure. In parallel to the absorption changes, fast quenching of the fluorescence emission takes place. From the quantitative point of view, the best sensitivity is displayed by compound 1a, which can detect trace water with a limit of detection (LOD) of 0.003% vol. in acetone, and 0.004% vol. in acetonitrile, as determined by fluorescence spectroscopy. An interesting advantage of the sensors here reported is that the absorption changes taking place after the addition of water occur in the range 600–800 nm, which is uncommon in this research field. And mechanistically it has been concluded that the role of water is not to act as an acid, donating protons to a previously deprotonated sensor as in most reported sensors, but to act as a base, deprotonating directly the pyrylium dye, due to the presence of a phenolic functionality in its structure.

Luminescent Rhenium(I)tricarbonyl Complexes Containing Different Pyrazoles and Their Successive Deprotonation Products: CO2 Reduction Electrocatalysts.

Cationic fac-[Re(CO)3(pz*H)(pypzH)]OTf (pz*H = pyrazole, pzH; 3,5-dimethylpyrazole, dmpzH; indazole, indzH; 3-(2-pyridyl)pyrazole, pypzH) were obtained from fac-[ReBr(CO)3(pypzH)] by halide abstraction with AgOTf and subsequent addition of the corresponding pyrazole. Successive deprotonation with Na2CO3 and NaOH gave neutral fac-[Re(CO)3(pz*H)(pypz)] and anionic Na{fac-[Re(CO)3(pz*)(pypz)]} complexes, respectively. Cationic fac-[Re(CO)3(pz*H)(pypzH)]OTf, neutral complexes fac-[Re(CO)3(pz*H)(pypz)], and fac-[Re(CO)3(pypz)2Na] were subjected to photophysical and electrochemical studies. They exhibit phosphorescent decays from a prevalently 3MLCT excited state with quantum yields (Φ) in the range between 0.03 and 0.58 and long lifetimes (τ from 220 to 869 ns). The electrochemical behavior in Ar atmosphere of cationic and neutral complexes indicates that the oxidation processes assigned to ReI → ReII occurs at lower potentials for the neutral complex compared to cationic complex. The reduction processes occur at the ligands and do not depend on the charge of the complexes. The electrochemical behavior in CO2 saturated media is consistent with CO2 electrocatalyzed reduction, where the values of the catalytic activity [icat(CO2)/icat(Ar)] ranged from 2.7 to 11.5 (compared to 8.1 for fac-[Re(CO)3Cl(bipy)] studied as a reference). Controlled potential electrolysis for the pyrazole cationic (3a) and neutral (4a) complexes after 1 h affords CO in faraday yields of 61 and 89%, respectively. These values are higher for indazole complexes and may be related to the acidity of the coordinated pyrazole.

Unsymmetrical cationic porphyrin-cyclodextrin bioconjugates for photoinactivation of Escherichia coli.

Photodynamic inactivation (PDI) of microorganisms has been used for the treatment of bacterial infection. PDI is based on the combination of three non-toxic elements: a photosensitizer (PS), light and molecular oxygen, which lead to the formation of reactive oxygen species (ROS) that cause lethal oxidative damage into the target pathogenic bacteria. For that, clinical approved tetrapyrrolic macrocycles, with particular emphasis on photoactive porphyrin (Por) dyes, have been used as PS in PDI for different biomedical applications. Two novel unsymmetrical free-base thiopyridyl Pors conjugated with α- or γ-CD units (Pors 2 and 3) were prepared and the corresponding cationic ones (Pors 2a and 3a) were assessed as water-soluble photosensitizer (PS) agents by photophysical, photochemical and E. coli photobiological studies. The presence of the CD unit and the positive charges on the Por periphery (2a and 3a) enhance their solubility in aqueous media. The photoactivity of the two cationic Pors 2a and 3a ensures their potential as PDI drugs against Gram-negative bacteria model, a bioluminescent E. coli, which the best PDI efficiency was determined for Por 3a that achieved the highest bacterial reduction of 4.0 log10 (ANOVA, p < 0.0001), reaching the detection limit of the method after 15 min.

Stimuli-Responsive Supramolecular Coaggregation and Disaggregation of Host-Guest Conjugates Having a Disulfide Linkage.

Water-soluble cationic and anionic cyclophanes (1a and 2a, respectively) having a dabsyl group with a cleavable disulfide linkage were synthesized as a host-guest conjugate covalently bound with both host and guest components. Self-inclusion phenomena but not self-aggregation behaviors were observed for each cyclophane in aqueous media. Each cyclophane includes its own dabsyl moiety (guest component) in its macrocyclic cavity (host component) through hydrophobic interaction. When 1 equiv. of cationic 1a was added to an aqueous solution of anionic 2a, however, supramolecular coaggregates formed spontaneously through host-guest complexation. As regard the supramolecular coaggregates, the existence of larger particles was confirmed by DLS measurements and TEM observation. The hydrophobic interaction between the dabsyl moiety and macrocyclic cavity and electrostatic interactions between 1a and 2a play important roles in the supramolecular coaggregate formation. Each cyclophane having a cleavable disulfide linkage was easily transformed to the corresponding thiols by reducing reagents such as DTT, which was confirmed by MALDI-TOF MS. Disaggregation of the supramolecular coaggregates composed of 1a and 2a was successfully performed upon addition of DTT, with release of the thiol derivative of dabsyl. Such disaggregation of the coaggregates was also conducted by other external stimuli such as salts and competitive guests.

Isobutene (co)polymerization initiated by rare-earth metal cationic catalysts

Isobutene (co)polymerizations by rare-earth metal cationic complexes were studied. The half-sandwich scandium and lutetium complexes 1a and 1c activated by one equivalent of [Ph3C][B(C6F5)4], displayed high activity for isobutene polymerization at −30 °C. Its yttrium analogue 1b, the constrained geometry complexes 3 and 4 and the yttrium metallocene 5 showed lower activities. Another half-sandwich scandium complex 2 and non-Cp complex 6 were nearly inert. The resultant molecular weights produced by cationic initiator 1a increased from 2.45 × 104 to 27.8 × 104 g/mol with temperature declining from 20 °C to −50 °C. Despite increment of isobutene/1a mole ratio from 3000:1 to 30000:1, the resultant molecular weights still fell within the scope of 20.0 × 104–25.0 × 104 g/mol. The cationic species 1a/[Ph3C][B(C6F5)4] is not an efficient initiator for isobutene copolymerization with isoprene, but if the cationic species is first treated by isobutene or the dicationic species 1a/2[Ph3C][B(C6F5)4] is applied, the copolymerization can reach high conversion.

Increasing Lewis acidity in perchlorophenyl derivatives of antimony

The improved synthesis of the homoleptic perchlorophenyl stibine (C6Cl5)3Sb (1a) has enabled us to obtain detailed spectroscopic and structural information. In contrast to the planar structure shown by the nitrogen homologue (C6Cl5)3N, the antimony compound 1a shows unmistakable pyramidal structure (C–Sb–C 100.9(2)°, av.) with slightly elongated Sb–C bonds (219.6(4) pm, av.) with respect to the non-chlorinated model compound Ph3Sb. The Sb–C bonds shorten upon oxidation, as it is found in the oxidized compound (C6Cl5)3SbCl2 (2a). A single isomer is stereoselectively obtained for this hypervalent compound 2a, namely that with the Cl ligands in axial positions. This neutral, hypervalent compound (2a) is found to dissociate chloride in the gas phase (MS) giving rise to the [(C6Cl5)3SbCl]+ cation (3a). According to theoretical calculations this cation should have nearly tetrahedral structure and behave as a Lewis superacid. The structural properties and Lewis acidity of compounds 1a–3a are compared with those calculated for their corresponding isoelectronic tin derivatives (1b–3b).

Heteroarylcarbene-Arylnitrene Radical Cation Isomerizations.

5-Phenyltetrazole 1e is an important source of phenylnitrene or the phenylnitrene radical cation ( m/ z 91) under thermal, photochemical, and electron impact conditions. Similarly, 3- or 4-(5-tetrazolyl)pyridines 12b,c yield pyridylnitrene radical cations 9a•+ ( m/ z 92) upon electron impact. In contrast, 2-(5-tetrazolyl)pyridine 12a•+ generates 2-pyridyldiazomethane 24•+ and 2-pyridylcarbene 26•+ radical cations ( m/ z 119 and 91) upon electron impact. The 2-pyridylcarbene radical cation undergoes a carbene-nitrene rearrangement to yield the phenylnitrene radical cation. Calculations at the B3LYP/6-311G(d,p) level have revealed facile H-transfer from the tetrazole to the pyridine ring in 2-(5-tetrazolyl)pyridine, 12a•+ → 21•+, taking place in the radical cations. Subsequent losses of N2 generate the pyridinium diazomethyl radical 22•+ or pyridinium-2-carbyne 23•+. These two ions can isomerize to 2-pyridyldiazomethane 24•+ and 2-pyridylcarbene 26•+, the latter rearranging to the phenylnitrene radical cations 9a•+. 13C-labeling of the tetrazole rings confirmed that 2-(5-tetrazolyl)pyridine 12a generates 2-pyridylcarbene/phenylnitrene radical cations retaining the 13C label, but 4-(5-tetrazolyl)pyridine 12c generates 4-pyridylnitrene 18c•+, which has lost the 13C label. 2-Pyridylcarbene/phenylnitrene radical cations ( m/ z 91) also constitute the base peak in the mass spectrum of 1,2,3-triazolo[1,5- a]pyridine 34. Similarly, 4-pyridylnitrene radical cation 18c•+ or its isomers ( m/ z 92) is obtained from 1,2,3-triazolo[1,5- a]pyrazine 36. Several other α-heteroaryltetrazoles behave in the same way as 2-(5-tetrazolyl)pyridine, yielding heteroarylcarbene/arylnitrene radical cations in the mass spectrometer, and this was confirmed by 13C-labeling in the case of 1-(5-tetrazolyl)isoquinoline 42-13C. In general, 5-aryltetrazoles generate arylnitrene radical cations under electron impact, but α-heteroaryltetrazoles generate α-heteroarylcarbene radical cations.

Anion-Binding-Induced Electrochemical Signal Transduction in Ferrocenylimidazolium: Combined Electrochemical Experimental and Theoretical Investigation.

Five ferrocene alkymethylimidazolium cations 1a–1d and 2 with different alkyl spacer lengths were reinvestigated using voltammetry and density functional theory (DFT) calculations. The voltammetric responses of ligand 2 toward various anions are described in detail. An interesting and unprecedented finding from both experimental and theoretical studies is that coupled electron and intramolecular anion (F−) transfer may be present in these molecules. In addition, it was also observed that, in these studied molecules, the electrostatic attraction interaction toward F− would effectively vanish beyond 1 nm, which was previously reported only for cations.

An Extremely Electron Poor Cationic Triazoliumylidene N-Heterocyclic Carbene: Experimental and Computational Studies

The electronic properties of the long-known cationic 1,2,4-triazoliumylidene 3a have been determined. The 77Se NMR chemical shift of its Se adduct 9 (δ = 138 ppm) indicates that 3a is only moderately π-acidic. M(CO)2Cl complexes of 3a (M = Rh, Ir) allowed the IR spectroscopic determination of a TEP value of 2073 cm–1, the highest value known to date for a N-heterocyclic carbene (NHC). The properties of cationic 3a were compared to those of the related neutral triazolylidene 5, which was prepared for comparison. Density functional theory calculations support the experimental findings. Overall, the cationic carbene 3a has to be considered a very poor σ-donor. Nevertheless, 3a is able to form di- (19) and even tricationic bis-NHC complexes (20 and 21).

Synthesis, characterization, crystal structure and DNA-binding study of four cadmium(II) pyridine-carboxamide complexes

Treatment of perchlorate or nitrate salt of cadmium(II) with carboxamide derivatives (L) generated four novel mononuclear metal complexes, represented as [Cd(L )4](ClO4)2 (1a and 1b) and [Cd(L)2(ONO2)2] (2a and 2b) in appreciable yields (L = L 1 = N-(furan-2-ylmethyl)-2-pyridine carboxamide and L = L 2 = N-(thiophen-2-ylmethyl)-2-pyridine carboxamide). The complexes have been characterized by FT-IR, UV-Visible, elemental analysis and single crystal X-ray crystallographic analysis which revealed eight coordinated cadmium ions, but in different coordination environments, depending on the counter anion used. In addition, electronic absorption, fluorescence spectroscopy and viscosity measurements revealed a significant interaction of the four complexes with CT-DNA via intercalative/groove binding mode. The intrinsic binding constant K b obtained varies from 0.4 × 10 4 to 1.11 × 10 5 M−1. The results suggest that neutral complexes 2a and 2b bind to DNA in an intercalative mode. On the other hand, cationic complexes 1a and 1b bind with DNA via weak electrostatic/covalent interaction. Synthesis and characterization of four mononuclear eight coordinated cadmium(II) complexes with newly explored carboxamide derivatives and study of interaction with calf-thymus DNA are reported. The results suggest that neutral complexes 2a and 2b bind to DNA in an intercalative mode. On the other hand, cationic complexes 1a and 1b interact with DNA via weak intercalative or groove binding mode.

Synthesis and evaluation of 18F-trifluoroborate derivatives of triphenylphosphonium for myocardial perfusion imaging

Four trifluoroborate derivatives of phosphonium cations 2a–d were radiolabeled with fluorine-18 (18F) and evaluated for imaging myocardial perfusion with positron emission tomography (PET). Tracers were radiolabeled simply via 18F–19F isotope exchange reaction in acidic (pH 2) aqueous solution. On average, [18F]2a–d were obtained in 10–17% non-decay-corrected radiochemical yield with 25.9–48.1GBq/μmol specific activity, and >96% radiochemical purity. In vitro stability study showed no decomposition of [18F]2a–d after being incubated in mouse plasma for up to 2h. Myocardial uptake in mice was visualized in PET images by using [18F]2b–d but not [18F]2a. [18F]2a–d were stable against in vivo defluorination as no significant bone uptake was observed. Despite sub-optimal heart uptake of [18F]2b–d, we successfully demonstrated that 18F–19F isotope exchange reaction on trifluoroborates could be a promising strategy for the design of potential 18F-labeled tracers even for intracellular targets.

Synthesis of coumarin-appended cyclophanes and evaluation of their complexation with myoglobin

Coumarin-appended cyclophanes bearing positively or negatively charged side chains were synthesized as a water-soluble host (1a or 1b, respectively). Host 1a and 1b showed fluorescence bands with fluorescence maxima at 404 nm originated from coumarin moiety. As a host for guest molecules by using macrocyclic cavity, cationic host 1a binds anionic guests such as 6-p-toluidinonaphthalene-2-sulfonate (TNS), 6-anilinonaphthalene-2-sulfonate (2,6-ANS), and 8-anilinonaphthalene-1-sulfonate (1,8-ANS) more strongly than anionic host 1b, reflecting intermolecular electrostatic interactions. In addition, both host 1a and 1b showed protein surface recognition and fluorescence response toward myoglobin, a small and globular protein. The fluorescence intensity originating from the hosts decreased upon the addition of myoglobin, reflecting the formation of 1a- and 1b-myoglobin complexes. On the other hand, such fluorescence response of 1a and 1b was almost negligible for other proteins such as egg white albumin, bovine serum albumin, human albumin, concanavaline A, fibrinogen, γ-globlin, peanut agglutinin, trypsin, and lysozyme.

An NHC-Stabilized Silicon Analogue of Acylium Ion: Synthesis, Structure, Reactivity, and Theoretical Studies.

The silicon analogues of an acylium ion, namely, sila-acylium ions 2a and 2b [RSi(O)(NHC)2]Cl stabilized by two N-heterocyclic carbenes (NHC = 1,3,4,5-tetramethylimidazol-2-ylidene), and having chloride as a countercation were successfully synthesized by the reduction of CO2 using the donor stabilized silyliumylidene cations 1a and 1b [RSi(NHC)2]Cl (1a, 2a; R = m-Ter = 2,6-Mes2C6H3, Mes = 2,4,6-Me3C6H2 and 1b, 2b; R = Tipp = 2,4,6-iPr3C6H2). Structurally, compound 2a features a four coordinate silicon center together with a double bond between silicon and oxygen atoms. The reaction of sila-acylium ions 2a and 2b with water afforded different products which depend on the bulkiness of aryl substituents. Although the exposure of 2a to H2O afforded a stable silicon analogue of carboxylate anion as a dimer form, [m-TerSi(O)O]2(2-)·2[NHC-H](+) (3), the same reaction with the less bulkier triisopropylphenyl substituted sila-acylium ion 2b afforded cyclotetrasiloxanediol dianion [{TippSi(O)}4{(O)OH}2](2-)·2[NHC-H](+) (4). Metric and DFT (Density Functional Theory) evidence support that 2a and 2b possess strong Si═O double bond character, while 3 and 4 contain more ionic terminal Si-O bonds. Mechanistic details of the formation of different (SiO)n (n = 2, 3, 4) core rings were explored using DFT to explain the experimentally characterized products and a proposed stable intermediate was identified with mass spectrometry.