Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes.

Cu(II) complexes with 2,2':6',2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl2(Ln)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (Cu1a and Cu1b) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).

Copper(II) Complexes with 2,2':6',2″-Terpyridine Derivatives Displaying Dimeric Dichloro-µ-Bridged Crystal Structure: Biological Activities from 2D and 3D Tumor Spheroids to In Vivo Models.

Eight 2,2':6',2″-terpyridines, substituted at the 4'-position with aromatic groups featuring variations in π-conjugation, ring size, heteroatoms, and methoxy groups, were employed to enhance the antiproliferative potential of [Cu2Cl2(R-terpy)2](PF6)2. Assessing the cytotoxicity in A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), and HCT116DoxR (colorectal carcinoma resistant to doxorubicin) and normal primary fibroblasts revealed that Cu(II) complexes with 4-quinolinyl, 4-methoxy-1-naphthyl, 2-furanyl, and 2-pyridynyl substituents showed superior therapeutic potential in HCT116DoxR cells with significantly reduced cytotoxicity in normal fibroblasts (42-129× lower). Besides their cytotoxicity, the Cu(II) complexes are able to increase intracellular ROS and interfere with cell cycle progression, leading to cell death by apoptosis and autophagy. Importantly, they demonstrated antimetastatic and antiangiogenic properties without in vivo toxicity. In accordance with their nuclear accumulation, the Cu(II) complexes are able to cleave pDNA and interact with bovine serum albumin, which is a good indication of their ability for internalization and transport toward tumor cells.

Flexible, Transparent, and Cytocompatible Nanostructured Indium Tin Oxide Thin Films for Bio-optoelectronic Applications.

Electrical stimulation has been used successfully for several decades for the treatment of neurodegenerative disorders, including motor disorders, pain, and psychiatric disorders. These technologies typically rely on the modulation of neural activity through the focused delivery of electrical pulses. Recent research, however, has shown that electrically triggered neuromodulation can be further enhanced when coupled with optical stimulation, an approach that can benefit from the development of novel electrode materials that combine transparency with excellent electrochemical and biological performance. In this study, we describe an electrochemically modified, nanostructured indium tin oxide/poly(ethylene terephthalate) (ITO/PET) surface as a flexible, transparent, and cytocompatible electrode material. Electrochemical oxidation and reduction of ITO/PET electrodes in the presence of an ionic liquid based on d-glucopyranoside and bistriflamide units were performed, and the electrochemical behavior, conductivity, capacitance, charge transport processes, surface morphology, optical properties, and cytocompatibility were assessed in vitro. It has been shown that under selected conditions, electrochemically modified ITO/PET films remained transparent and highly conductive and were able to enhance neural cell survival and neurite outgrowth. Consequently, electrochemical modification of ITO/PET electrodes in the presence of an ionic liquid is introduced as an effective approach for tailoring the properties of ITO for advanced bio-optoelectronic applications.

A method for the synthesis of unsymmetric bisphosphoric analogs of α-amino acids.

Herein, we describe the first universal strategy for the synthesis of unsymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogs of N-protected 1-aminobisphosphonates. The proposed user-friendly procedure, based on a one-pot reaction of the α-ethoxy derivatives of phosphorus analogs of protein and non-protein α-amino acids with triphenylphosphonium tetrafluoroborate and an appropriate phosphorus nucleophile (diethyl phenylphosphonite or methyl diphenylphosphinite), provides good to very good yields of 53-91% under mild catalyst-free conditions (temperature: rt to 40 °C, time: 1 to 6 hours). The progress of the transformation, running through the corresponding phosphonium salt as a reactive intermediate, was monitored by 31P NMR spectroscopy, which is a convenient tool for the identification of the transient species formed here. In this paper, we present the full characteristics of the spectroscopic properties of all 13 synthesized models of structurally diverse N-protected unsymmetric bisphosphoric analogs of α-amino acids. Therefore, these results contribute to increasing the practical applicability of our recently reported synthesis protocol of symmetric models of α-aminobisphosphonates derivatives and thus justify its universality.

S/Se-Terchalcogenophene-C60 Dyads: Synthesis and Characterization of Optical and Photosensitizing Properties.

Fullerenes have been long investigated for application as singlet oxygen sources. Even though they possess high photosensitizing efficiency, their practical use is still limited, mostly because of insufficient absorption of visible and/or near-infrared light. This limitation can be overcome by introducing organic chromophores that absorb longer-wavelength light, either by covalent attachment to C60 or by its encapsulation in a polymeric matrix. In this work, we investigated the photosensitizing properties of the C60 molecule functionalized with organic units comprising thiophene or selenophene rings. The chemical structures of the synthesized dyads were characterized by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The influence of the S/Se atoms and vinyl linkage between the organic unit and C60 on the absorptive and emissive properties of the dyads was investigated and correlated with their photosensitizing activity. For the latter, we used a standard chemical singlet oxygen trap. A selected dyad C60ThSe2 was also applied as a source of singlet oxygen in a model photocatalyzed synthesis of the fine chemical juglone from 1,5-dihydroxynapthalene.

1-Hydroxyalkylphosphonium Salts-Synthesis and Properties.

An efficient and convenient method for the synthesis of 1-hydroxyalkylphosphonium salts is described. Reactions were carried out at room temperature, in a short time, and without chromatography for product isolation. The properties of the obtained phosphonium salts were examined and discussed. In this paper, primary attention was paid to the stability of phosphonium salts, depending on the structure of the aldehydes used as substrates in their preparation. Other conditions such as the type of solvent, temperature, and molar ratio of the substrates were also investigated. Finally, the high reactivity of 1-hydroxyalkylphosphonium salts was demonstrated in reactions with amide-type substrates and (hetero)aromatic compounds. The developed step-by-step procedure (with the isolation of 1-hydroxyphosphonium salts) was compared to the one-pot protocol (in situ formation of such phosphonium salts).

Eco-Conscious Approach to Thermoresponsive Star-Comb and Mikto-Arm Polymers via Enzymatically Assisted Atom Transfer Radical Polymerization Followed by Ring-Opening Polymerization.

This study explores the synthesis, characterization, and application of a heterofunctional initiator derived from 2-hydroxypropyl cyclodextrin (HP-ß-CD), having eight bromoester groups and thirteen hydroxyl groups allowing the synthesis of mikto-arm star-shaped polymers. The bromoesterification of HP-ß-CD was achieved using α-bromoisobutyryl bromide as the acylation reagent, modifying the cyclodextrin (CD) molecule as confirmed by electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy analysis, and differential scanning calorimetry (DSC) thermograms. The initiator's effectiveness was further demonstrated by obtaining star-comb and mikto-arm polymers via an enzymatically assisted atom transfer radical polymerization (ATRP) method and subsequent ring-opening polymerization (ROP). The ATR polymerization quality and control depended on the type of monomer and was optimized by the way of introducing the initiator into the reaction mixture. In the case of ATRP, high conversion rates for poly(ethylene oxide) methyl ether methacrylate (OEOMA), with molecular weights (Mn) of 500 g/mol and 300 g/mol, were achieved. The molecular weight distribution of the obtained polymers remained in the range of 1.23-1.75. The obtained star-comb polymers were characterized by different arm lengths. Unreacted hydroxyl groups in the core of exemplary star-comb polymers were utilized in the ROP of ε-caprolactone (CL) to obtain a hydrophilic mikto-arm polymer. Cloud point temperature (TCP) values of the synthesized polymers increased with arm length, indicating the polymers' reduced hydrophobicity and enhanced solvation by water. Atomic force microscopy (AFM) analysis revealed the ability of the star-comb polymers to create fractals. The study elucidates advancements in the synthesis and utilization of hydrophilic sugar-based initiators for enzymatically assisted ATRP in an aqueous solution for obtaining complex star-comb polymers in a controlled manner.

Photoinduced Processes in Rhenium(I) Terpyridine Complexes Bearing Remote Amine Groups: New Insights from Transient Absorption Spectroscopy.

Photophysical properties of two Re(I) complexes [ReCl(CO)3(R-C6H4-terpy-κ2N)] with remote amine groups, N-methyl-piperazinyl (1) and (2-cyanoethyl)methylamine (2), were investigated. The complexes show strong absorption in the visible region corresponding to metal-to-ligand charge transfer (1MLCT) and intraligand-charge-transfer (1ILCT) transitions. The energy levels of 3MLCT and 3ILCT excited-states, and thus photoluminescence properties of 1 and 2, were found to be strongly affected by the solvent polarity. Compared to the parent chromophore [ReCl(CO)3(C6H5-terpy-κ2N)] (3), both designed complexes show significantly prolonged (by 1-2 orders of magnitude) phosphorescence lifetimes in acetonitrile and dimethylformamide, contrary to their lifetimes in less polar chloroform and tetrahydrofuran, which are comparable to those for 3. The femtosecond transient absorption (fsTA) measurements confirmed the interconversion between the 3MLCT and 3ILCT excited-states in polar solvents. In contrast, the emissive state of 1 and 2 in less polar environments is of predominant 3MLCT nature.

Impact of the Anthryl Linking Mode on the Photophysics and Excited-State Dynamics of Re(I) Complexes [ReCl(CO)3(4'-An-terpy-κ2N)].

Rhenium(I) complexes with 2,2':6',2″-terpyridines (terpy) substituted with 9-anthryl (1) and 2-anthryl (2) were synthesized, and the impact of the anthryl linking mode on the ground- and excited-state properties of resulting complexes [ReCl(CO)3(4'-An-terpy-κ2N)] (An─anthryl) was investigated using a combination of steady-state and time-resolved optical techniques accompanied by theoretical calculations. Different attachment positions of anthracene modify the overlap between the molecular orbitals and thus the electronic coupling of the anthracene and {ReCl(CO)3(terpy-κ2N)} chromophores. Following the femtosecond transient absorption, the lowest triplet excited state of both complexes was found to be localized on the anthracene chromophore. The striking difference between 1 and 2 concerns the triplet-state formation dynamics. A more planar geometry of 2-anthryl-terpy (2), and thus better electronic communication between the anthracene and {ReCl(CO)3(terpy-κ2N)} chromophores, facilitates the formation of the 3An triplet state. In steady-state photoluminescence spectra, the population ratio of 3MLCT and 3An was found to be dependent not only on the anthryl linking mode but also on solvent polarity and excitation wavelengths. In dimethyl sulfoxide (DMSO), compounds 1 and 2 excited with λexc > 410 nm show both 3MLCT and 3An emissions, which are rarely observed. Additionally, the abilities of the designed complexes for 1O2 generation and light emission under the external voltage were preliminary examined.

A fundamental role of the solvent polarity and remote substitution of the 2-(4-R-phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline framework in controlling the ground- and excited-state properties of Re(I) chromophores [ReCl(CO)3(R-C6H4-imphen)].

A series of Re(I) carbonyl complexes with the 1H-imidazo[4,5-f][1,10]phenanthroline (imphen) ligand functionalized with electron-donating amine groups attached to the imidazole ring via phenylene linkages were designed to investigate the impact of remote amine substituents on the ground- and excited-state properties of [ReCl(CO)3(R-C6H4-imphen)]. The complexes [ReCl(CO)3(R-C6H4-imphen)] belong to the family of [ReCl(CO)3(diimine)] systems, but contrary to strongly related phenanthroline Re(I) carbonyl complexes with a rich history in coordination chemistry, they are really sparse. The effects of electron-rich N-donor groups in [ReCl(CO)3(R-C6H4-imphen)] were fully studied with the use of cyclic voltammetry, absorbance and emission spectroscopy, and transient absorption spectroscopy, and they were simulated by density functional theory. The attachment of electron-rich amine groups to C6H5-imphen resulted in a decrease in oxidation potentials and a noticeable bathochromic shift of the longest absorption wavelength of [ReCl(CO)3(R-C6H4-imphen)] compared with the parent compound [ReCl(CO)3(C6H5-imphen)] due to a significant destabilization of the HOMO energy level. Regarding the excited-state properties, the triplet emission red-shift of [ReCl(CO)3(R-C6H4-imphen)] induced by appended electron-rich N-donor groups was accompanied by a significant increase in excited state lifetimes, up to a 12-fold enhancement compared with the parent chromophore. The lifetime prolongation of [ReCl(CO)3(R-C6H4-imphen)] bearing amine substituents was rationalized by the population of the ligand-localized triplet state, while the solvent-dependent photoluminescence characteristics of [ReCl(CO)3(R-C6H4-imphen)] were correlated with strong hydrogen bonding interactions between the acidic imidazole NH proton and highly polar solvents. The present findings are of high importance for understanding and controlling the excited-state nature of transition metal complexes.

PA-12-Zirconia-Alumina-Cenospheres 3D Printed Composites: Accelerated Ageing and Role of the Sterilisation Process for Physicochemical Properties.

The aim of this study was to conduct artificial ageing tests on polymer-ceramic composites prepared from polyamide PA-12 polymer matrix for medical applications and three different variants of ceramic fillers: zirconia, alumina and cenospheres. Before ageing, the samples were subjected to ethyl oxide sterilization. The composite variants were prepared for 3D printing using the fused deposition modeling method. The control group consisted of unsterilized samples. Samples were subjected to artificial ageing in a high-pressure autoclave. Ageing conditions were calculated from the modified Hammerlich Arrhenius kinetic equation. Ageing was carried out in artificial saliva. After ageing the composites were subjected to mechanical (tensile strength, hardness, surface roughness) testing, chemical and structural (MS, FTIR) analysis, electron microscopy observations (SEM/EDS) and absorbability measurements.

Design, Synthesis and Preliminary Evaluation of the Cytotoxicity and Antibacterial Activity of Novel Triphenylphosphonium Derivatives of Betulin.

For several decades, natural products have been widely researched and their native scaffolds are the basis for the design and synthesis of new potential therapeutic agents. Betulin is an interesting biologically attractive natural parent molecule with a high safety profile and can easily undergo a variety of structural modifications. Herein, we describe the synthesis of new molecular hybrids of betulin via covalent linkage with an alkyltriphenylphosphonium moiety. The proposed strategy enables the preparation of semi-synthetic derivatives (28-TPP⊕ BN and 3,28-bisTPP⊕ BN) from betulin through simple transformations in high yields. The obtained results showed that the presence of a lipophilic cation improved the solubility of the tested analogs compared to betulin, and increased their cytotoxicity. Among the triphenylphosphonium derivatives tested, analogs 7a (IC50 of 5.56 µM) and 7b (IC50 of 5.77 µM) demonstrated the highest cytotoxicity against the colorectal carcinoma cell line (HCT 116). TPP⊕-conjugates with betulin showed antimicrobial properties against Gram-positive reference Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis ATCC 12228 bacteria, at a 200 µM concentration in water. Hence, the conjugation of betulin's parent backbone with a triphenylphosphonium moiety promotes transport through the hydrophobic barriers of the mitochondrial membrane, making it a promising strategy to improve the bioavailability of natural substances.

One-Pot and Catalyst-Free Transformation of N-Protected 1-Amino-1-Ethoxyalkylphosphonates into Bisphosphonic Analogs of Protein and Non-Protein α-Amino Acids.

Herein, we describe the development of one-pot transformation of α-ethoxy derivatives of phosphorus analogs of protein and non-protein α-amino acids into biologically important N-protected 1-aminobisphosphonates. The proposed strategy, based on the three-component reaction of 1-(N-acylamino)-1-ethoxyphosphonates with triphenylphosphonium tetrafluoroborate and triethyl phosphite, facilitates good to excellent yields under mild reaction conditions. The course of the reaction was monitored by 31P NMR spectroscopy, allowing the identification of probable intermediate species, thus making it possible to propose a reaction mechanism. In most cases, there is no need to use a catalyst to provide transformation efficiency, which increases its attractiveness both in economic and ecological terms. Furthermore, we demonstrate that the one-pot procedure can be successfully applied for the synthesis of structurally diverse N-protected bisphosphonic analogs of α-amino acids. As shown, the indirect formation of the corresponding phosphonium salt as a reactive intermediate during the conversion of 1-(N-acylamino)-1-ethoxyphosphonate into a 1-aminobisphosphonate derivative is a crucial component of the developed methodology.

Synthesis and Preliminary Evaluation of the Cytotoxicity of Potential Metabolites of Quinoline Glycoconjugates.

The design of prodrugs is one of the important strategies for selective anti-cancer therapies. When designing prodrugs, attention is paid to the possibility of their targeting tumor-specific markers such as proteins responsible for glucose uptake. That is why glycoconjugation of biologically active compounds is a frequently used strategy. Glycoconjugates consisting of three basic building blocks: a sugar unit, a linker containing a 1,2,3-triazole ring, and an 8-hydroxyquinoline fragment was described earlier. It is not known whether their cytotoxicity is due to whole glycoconjugates action or their metabolites. To check the biological activity of products that can be released from glycoconjugates under the action of hydrolytic enzymes, the synthetically obtained potential metabolites were tested in vitro for the inhibition of proliferation of HCT-116, MCF-7, and NHDF-Neo cell lines using the MTT assay. Research shows that for the full activity of glycoconjugates, the presence of all three building blocks in the structure of a potential drug is necessary. For selected derivatives, additional tests of targeted drug delivery to tumor cells were carried out using polymer nanocarriers in which they are encapsulated. This approach significantly lowered the determined IC50 values of the tested compounds and improved their selectivity and effectiveness.

Electrochemically Deposited Zinc (Tetraamino)phthalocyanine as a Light-activated Antimicrobial Coating Effective against S. aureus.

Light-activated antimicrobial coatings are currently considered to be a promising approach for the prevention of nosocomial infections. In this work, we present a straightforward strategy for the deposition of a photoactive biocidal organic layer of zinc (tetraamino)phthalocyanine (ZnPcNH2) in an electrochemical oxidative process. The chemical structure and morphology of the resulting layer are widely characterized by microscopic and spectroscopic techniques, while its ability to photogenerate reactive oxygen species (ROS) is investigated in situ by UV-Vis spectroscopy with α-terpinene or 1,3-diphenylisobenzofuran as a chemical trap. It is shown that the ZnPcNH2 photosensitizer retained its photoactivity after immobilization, and that the reported light-activated coating exhibits promising antimicrobial properties towards Staphyloccocus aureus (S. aureus).

In-Depth Studies of Ground- and Excited-State Properties of Re(I) Carbonyl Complexes Bearing 2,2':6',2″-Terpyridine and 2,6-Bis(pyrazin-2-yl)pyridine Coupled with π-Conjugated Aryl Chromophores.

In the current work, comprehensive photophysical and electrochemical studies were performed for eight rhenium(I) complexes incorporating 2,2':6',2″-terpyridine (terpy) and 2,6-bis(pyrazin-2-yl)pyridine (dppy) with appended 1-naphthyl-, 2-naphthyl-, 9-phenanthrenyl, and 1-pyrenyl groups. Naphthyl and phenanthrenyl substituents marginally affected the energy of the MLCT absorption and emission bands, signaling a weak electronic coupling of the appended aryl group with the Re(I) center. The triplet MLCT state in these complexes is so low lying relative to the triplet 3ILaryl that the thermal population of the triplet excited state delocalized on the organic chromophore is ineffective. The attachment of the electron-rich pyrenyl group resulted in a noticeable red shift and a significant increase in molar absorption coefficients of the lowest energy absorption of the resulting Re(I) complexes due to the contribution of intraligand charge-transfer (ILCT) transitions occurring from the pyrenyl substituent to the terpy/dppy core. At 77 K, the excited states of [ReCl(CO)3(Ln-κ2N)] with 1-pyrenyl-functionalized ligands were found to have predominant 3ILpyrene/3ILCTpyrene→terpy character. The 3IL/3ILCT nature of the lowest energy excited state of [ReCl(CO)3(4'-(1-pyrenyl)-terpy-κ2N)] was also evidenced by nanosecond transient absorption and time-resolved emission spectroscopy. Enhanced room-temperature emission lifetimes of the complexes [ReCl(CO)3(Ln-κ2N)] with 1-pyrenyl-substituted ligands are indicative of the thermal activation between 3MLCT and 3IL/3ILCT excited states. Deactivation pathways occurring upon light excitation in [ReCl(CO)3(4'-(1-naphthyl)-terpy-κ2N)] and [ReCl(CO)3(4'-(1-pyrenyl)-terpy-κ2N)] were determined by femtosecond transient absorption studies.

Vanadium(IV) Complexes with Methyl-Substituted 8-Hydroxyquinolines: Catalytic Potential in the Oxidation of Hydrocarbons and Alcohols with Peroxides and Biological Activity.

Methyl-substituted 8-hydroxyquinolines (Hquin) were successfully used to synthetize five-coordinated oxovanadium(IV) complexes: [VO(2,6-(Me)2-quin)2] (1), [VO(2,5-(Me)2-quin)2] (2) and [VO(2-Me-quin)2] (3). Complexes 1-3 demonstrated high catalytic activity in the oxidation of hydrocarbons with H2O2 in acetonitrile at 50 °C, in the presence of 2-pyrazinecarboxylic acid (PCA) as a cocatalyst. The maximum yield of cyclohexane oxidation products attained was 48%, which is high in the case of the oxidation of saturated hydrocarbons. The reaction leads to the formation of a mixture of cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone. When triphenylphosphine is added, cyclohexyl hydroperoxide is completely converted to cyclohexanol. Consideration of the regio- and bond-selectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicates that the oxidation proceeds with the participation of free hydroxyl radicals. The complexes show moderate activity in the oxidation of alcohols. Complexes 1 and 2 reduce the viability of colorectal (HCT116) and ovarian (A2780) carcinoma cell lines and of normal dermal fibroblasts without showing a specific selectivity for cancer cell lines. Complex 3 on the other hand, shows a higher cytotoxicity in a colorectal carcinoma cell line (HCT116), a lower cytotoxicity towards normal dermal fibroblasts and no effect in an ovarian carcinoma cell line (order of magnitude HCT116 > fibroblasts > A2780).

Dialkyl Succinates and Adipates as Alternative Plasticizers-Even More Efficient Synthesis.

As a result of strict regulations of phthalate plasticizers, alternative non-phthalate forms are desired and increasingly used. This work presents a synthetic method for alternative plasticizers (dialkyl succinates and adipates) via esterification of succinic and adipic acid with alcohols: butan-1-ol and 2-ethylhexan-1-ol. Ionic liquids were synthesized by the reaction of triethylamine with over-equimolar (1:2.7) amounts of sulfuric(VI) acid, which were used as an acidic catalyst and solvent. The two-phase liquid-liquid system was formed during the reaction due to immiscibility of the esters with the ionic liquid. This phenomenon is a driving force of this process, shifting the equilibrium toward the product formation. As a result, dialkyl succinates and adipates were obtained in high yields (99%) and selectivities (>99%), under mild reaction conditions at 70-80 °C and using a 4:1 molar ratio of alcohol to acid and 15 mol% of catalyst. The catalyst was recycled 10 times without any loss of activity. This alternative method is highly competitive: it involves a simple procedure for product isolation as well as a high yield and purity of the resulting esters. These advantages make this method sustainable and promising for industrial applications.

Outperformance in Acrylation: Supported D-Glucose-Based Ionic Liquid Phase on MWCNTs for Immobilized Lipase B from Candida antarctica as Catalytic System.

This study presents a highly efficient method of a synthesis of n-butyl acrylate via esterification of acrylic acid and n-butanol in the presence of supported ionic liquid phase (SILP) biocatalyst consisting of the lipase B from Candida antarctica (CALB) and multi-walled carbon nanotubes (MWCNTs) modified by D-glucose-based ionic liquids. Favorable reaction conditions (acrylic acid: n-butanol molar ratio 1:2, cyclohexane as a solvent, biocatalyst 0.150 g per 1 mmol of acrylic acid, temperature 25 °C) allowed the achievement of a 99% yield of n-butyl acrylate in 24 h. Screening of various ionic liquids showed that the most promising result was obtained if N-(6-deoxy-1-O-methoxy-α-D-glucopyranosyl)-N,N,N-trimethylammonium bis-(trifluoromethylsulfonyl)imide ([N(CH3)3GlcOCH3][N(Tf)2]) was selected in order to modify the outer surface of MWCNTs. The final SILP biocatalyst-CNTs-[N(CH3)3GlcOCH3][N(Tf)2]-CALB contained 1.8 wt.% of IL and 4.2 wt.% of CALB. Application of the SILP biocatalyst led to the enhanced activity of CALB in comparison with the biocatalyst prepared via physical adsorption of CALB onto MWCNTs (CNTs-CALB), as well as with commercially available Novozyme 435. Thus, the crucial role of IL in the stabilization of biocatalysts was clearly demonstrated. In addition, a significant stability of the developed biocatalytic system was confirmed (three runs with a yield of ester over 90%).

Synthesis of N-Protected 1-Aminoalkylphosphonium Salts from Amides, Carbamates, Lactams, or Imides.

This report describes the development and optimization of the one-pot method for the synthesis of N-protected 1-aminoalkylphosphonium salts based on the three-component coupling of aldehydes and either amides, carbamates, lactams, imides, or urea in the presence of triarylphosphonium salts. The proposed strategy is very efficient and easy to carry out even on a larger scale (20 g) in any typical laboratory. Most reactions occur at temperatures between 50 and 100 °C in a short time (1-2 h) without requiring any catalyst, and simple workup procedures afford good to excellent yields. The exceptions are condensations with imides, which require much higher temperatures (150-170 °C) and longer reaction times (even 30 h). The possibility of carrying out the synthesis under solvent-free conditions (neat reactions) is also demonstrated. It is especially important for less reactive substrates (imides), and reactions required high temperature (or generally harsher conditions). Finally, we prove the developed one-pot methodology can be successfully applied for the synthesis of structurally diverse N-protected 1-aminoalkylphosphonium salts. Mechanistic studies showed the intermediate products of described couplings are 1-hydroxyalkylphosphonium salts, not N-hydroxyalkylamides, -imides, etc., as initially expected.