Design of New Bis(1,2,3-triazol-1-yl)methane-Based Nitrogen Ligands: Synthesis and Coordination Chemistry.

The reaction between bis(1,2,3-triazol-1-yl)methane derivatives and nBuLi and various aldehydes, yielded novel neutral ligand precursors incorporating alcohol functional groups. The resulting compounds exhibited distinct characteristics depending on the steric hindrance of the aldehyde employed. In instances where aromatic aldehydes were utilized, functionalization occurred at the methine group bridging both triazole rings. Conversely, the use of pivalic aldehyde prompted functionalization at the C5 position of the triazole ring. These compounds were subsequently employed as ligand precursors in the synthesis of organometallic aluminum and zinc complexes, yielding dinuclear complexes with high efficiency. The structural elucidation of all compounds was accomplished through spectroscopic methods and validated by X-ray crystallography. Preliminary catalytic investigations into the coupling reaction of cyclohexene oxide and CO2 revealed that aluminum and zinc complexes catalyzed the selective formation of polyether and polycarbonate materials, respectively.

One-pot terpolymerization of CHO, CO2 and L-lactide using chloride indium catalysts.

Ring-opening copolymerization reactions of epoxides, carbon dioxide and cyclic esters to produce copolymers is a promising strategy to prepare CO2-based polymeric materials. In this contribution, bimetallic chloride indium complexes have been developed as catalysts for the copolymerization processes of cyclohexene oxide, carbon dioxide and L-lactide under mild reaction conditions. The catalysts displayed good catalytic activity and excellent selectivity towards the preparation of poly(cyclohexene carbonate) (PCHC) at one bar CO2 pressure in the absence of a co-catalyst. Additionally, polyester-polycarbonate copolymers poly(lactide-co-cyclohexene carbonate) (PLA-co-PCHC) were obtained via an one-pot one-step route without the use of a co-catalyst. The degree of incorporation of carbon dioxide can be easily modulated by changing the CO2 pressure and the monomer feed, resulting in copolymers with different thermal properties.

Unexpected luminescence of non-conjugated biomass-based polymers: new approach in photothermal imaging.

Population growth, depletion of world resources and persistent toxic chemical production underline the need to seek new smart materials from inexpensive, biodegradable, and renewable feedstocks. Hence, "metal-free" ring-opening copolymerization to convert biomass carvone-based monomers into non-conventional luminescent biopolymers is considered a sustainable approach to achieve these goals. The non-conventional emission was studied in terms of steady-state and time-resolved spectroscopy in order to unravel the structure-properties for different carvone-based copolymers. The results highlighted the importance of the final copolymer folding structure as well as its environment in luminescent behavior (cluster-triggered emission). In all cases, their luminescent behavior is sensitive to small temperature fluctuations (where the minimum detected temperature is Tm ∼ 2 °C and relative sensitivity is Sr ∼ 6% °C) even at the microscopic scale, which endows these materials a great potential as thermosensitive smart polymers for photothermal imaging.

Synthesis of Nonisocyanate Poly(hydroxy)urethanes from Bis(cyclic carbonates) and Polyamines.

Nonisocyanate polyurethane materials with pending alcohol groups in the polymeric chain were synthesized by polyaddition reaction of bis(cyclic carbonates) onto diamines. For the platform molecule, 1,4-butanediol bis(glycidyl ether carbonate) (BGBC, 1) was used. The polyaddition reaction of 1 onto a wide range of diamines with different electronic and physical properties was explored. All PHUs were obtained quantitatively after 16 h at 80 °C temperature in MeCN as solvent. The low nucleophilicity of L-lysine has proven unable to ring-open the cyclic carbonate and, thus, no reaction occurred. The addition of DBU or TBD as the catalyst was tested and allows the obtention of the desired PHU. However, the presence of strong bases also led to the formation of polyurea fragments in the new PHU. The different poly(hydroxyurethane) materials were characterized using a wide range of spectroscopic techniques such as NMR, IR, MALDI-ToF, and using GPC studies. The thermal properties of the NIPUs were investigated by DSC and TGA analyses. Moreover, reactions employing different monomer ratios were performed, obtaining novel hydroxycarbamate compounds. Finally, sequential and one-pot experiments were also carried out to synthesize the PHUs polymers in one-step reaction.

Closing the loop in the synthesis of heteroscorpionate-based aluminium helicates: catalytic studies for cyclic carbonate synthesis.

Novel polynuclear helical aluminium complexes supported by bulky heteroscorpionate ligands have been developed and characterised. The use of bulkier ligands has allowed the isolation of unprecedented intermediates for the preparation of helical aluminium complexes. The catalytic activity of these aluminium complexes for cyclic carbonates formation has also been investigated under mild reaction conditions. The combination of complex 16 and Bu4NBr catalysed the synthesis of a broad range of monosubstituted cyclic carbonates from their corresponding epoxides and CO2 at 25 °C and one bar of CO2 pressure. This catalyst system also showed good catalytic activity for the preparation of disubstituted cyclic carbonates from internal epoxides and CO2.

Synthesis of High Molecular Weight Stereo-Di-Block Copolymers Driven by a Co-Initiator Free Catalyst.

Stereo-diblock copolymers of high molecular weight polylactide (PLA) were synthetized by the one pot-sequential addition method assisted by a heteroscorpionate catalyst without the need of a co-initiator. The alkyl zinc organometallic heteroscorpionate derivative (Zn(Et)(κ3-bpzteH)] (bpzteH = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1-para-tolylethoxide) proved to assist in the mechanism of reaction following a coordination-insertion process. Kinetic studies along with the linear correlation between monomer and number average molecular weight (Mn) conversion, and the narrow polydispersities supported the truly living polymerization character of the initiator, whereas matrix-assisted laser desorption/Ionization-time of flight (MALDI-TOF) studies showed a very low order of transesterification. The high stereo-control attained for the afforded high molecular weight derivatives was revealed by homonuclear decoupled 1H NMR spectra and polarimetry measurements. The nanostructure of the PLA derivatives was studied by both wide-angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC) and the stereocomplex phase of the PLA stereo-diblock copolymers was successfully identified.

A novel bis(pyrazolyl)methane compound as a potential agent against Gram-positive bacteria.

This study was designed to propose alternative therapeutic compounds to fight against bacterial pathogens. Thus, a library of nitrogen-based compounds bis(triazolyl)methane (1T-7T) and bis(pyrazolyl)methane (1P-11P) was synthesised following previously reported methodologies and their antibacterial activity was tested using the collection strains of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Moreover, the novel compound 2P was fully characterized by IR, UV-Vis and NMR spectroscopy. To evaluate antibacterial activity, minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) assays were carried out at different concentrations (2-2000 µg/mL). The MTT assay and Resazurin viability assays were performed in both human liver carcinoma HepG2 and human colorectal adenocarcinoma Caco-2 cell lines at 48 h. Of all the synthesised compounds, 2P had an inhibitory effect on Gram-positive strains, especially against S. aureus. The MIC and MBC of 2P were 62.5 and 2000 µg/mL against S. aureus, and 250 and 2000 µg/mL against E. faecalis, respectively. However, these values were > 2000 µg/mL against E. coli and P. aeruginosa. In addition, the MBICs and MBECs of 2P against S. aureus were 125 and > 2000 µg/mL, respectively, whereas these values were > 2000 µg/mL against E. faecalis, E. coli, and P. aeruginosa. On the other hand, concentrations up to 250 µg/mL of 2P were non-toxic doses for eukaryotic cell cultures. Thus, according to the obtained results, the 2P nitrogen-based compound showed a promising anti-Gram-positive effect (especially against S. aureus) both on planktonic state and biofilm, at non-toxic concentrations.

Ring-Opening Copolymerization of Cyclohexene Oxide and Cyclic Anhydrides Catalyzed by Bimetallic Scorpionate Zinc Catalysts.

The catalytic activity and high selectivity reported by bimetallic heteroscorpionate acetate zinc complexes in ring-opening copolymerization (ROCOP) reactions involving CO2 as substrate encouraged us to expand their use as catalysts for ROCOP of cyclohexene oxide (CHO) and cyclic anhydrides. Among the catalysts tested for the ROCOP of CHO and phthalic anhydride at different reaction conditions, the most active catalytic system was the combination of complex 3 with bis(triphenylphosphine)iminium as cocatalyst in toluene at 80 °C. Once the optimal catalytic system was determined, the scope in terms of other cyclic anhydrides was broadened. The catalytic system was capable of copolymerizing selectively and efficiently CHO with phthalic, maleic, succinic and naphthalic anhydrides to afford the corresponding polyester materials. The polyesters obtained were characterized by spectroscopic, spectrometric, and calorimetric techniques. Finally, the reaction mechanism of the catalytic system was proposed based on stoichiometric reactions.

Zinc-Catalyzed Hydroalkoxylation/Cyclization of Alkynyl Alcohols.

Despite the great interest in zinc catalysis for hydroelementation reactions, the use of zinc complexes as catalysts for the hydroalkoxylation of alkynyl alcohols has not been reported to date. Scorpionate zinc complexes have been successfully designed as precatalysts for the hydroalkoxylation reaction of alkynyl alcohols under mild reaction conditions. Zinc amide complex 8 has been shown to be an excellent precatalyst for the highly selective intramolecular hydroalkoxylation process to yield the corresponding exocyclic enol ethers. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl alcohol]. NMR spectroscopy and X-ray diffraction analysis provided evidence for the formation of an alkynyl zinc compound which has been shown to be a key intermediate in the hydroalkoxylation process. On the basis of the experimental results, a catalytic cycle is proposed.

Efficient Synthesis of Cyclic Carbonates from Unsaturated Acids and Carbon Dioxide and their Application in the Synthesis of Biobased Polyurethanes.

Bio-derived furan- and diacid-derived cyclic carbonates have been synthesized in high yields from terminal epoxides and CO2 . Furthermore, four highly substituted terpene-derived cyclic carbonates were isolated in good yields with excellent diastereoselectivity in some cases. Eleven new cyclic carbonates derived from 10-undecenoic acid under mild reaction conditions were prepared, providing the corresponding carbonate products in excellent yields. The catalyst system also performed the conversion of an epoxidized fatty acid n-pentyl ester into a cyclic carbonate under relatively mild reaction conditions (80 °C, 20 bar, 24 h). This bis(cyclic carbonate) was obtained in high yields and with different cis/trans ratios depending on the co-catalyst used. An allyl alcohol by-product was only observed as a minor product when bis(triphenylphosphine)iminium chloride was used as co-catalyst. Finally, two cyclic carbonates were used as building blocks for the preparation of non-isocyanate poly(hydroxy)urethanes by reaction with 1,4-diaminobutane.

Efficient Production of Poly(Cyclohexene Carbonate) via ROCOP of Cyclohexene Oxide and CO2 Mediated by NNO-Scorpionate Zinc Complexes.

New mono- and dinuclear chiral alkoxide/thioalkoxide NNO-scorpinate zinc complexes were easily synthesized in very high yields, and characterized by spectroscopic methods. X-ray diffraction analysis unambiguously confirmed the different nuclearity of the new complexes as well as the variety of coordination modes of the scorpionate ligands. Scorpionate zinc complexes 2, 4 and 6 were assessed as catalysts for polycarbonate production from epoxide and carbon dioxide with no need for a co-catalyst or activator under mild conditions. Interestingly, at 70 °C, 10 bar of CO2 pressure and 1 mol % of loading, the dinuclear thioaryloxide [Zn(bpzaepe)2{Zn(SAr)2}] (4) behaves as an efficient and selective one-component initiator for the synthesis of poly(cyclohexene carbonate) via ring-opening copolymerization of cyclohexene oxide (CHO) and CO2, affording polycarbonate materials with narrow dispersity values.

Bimetallic Zinc Catalysts for Ring-Opening Copolymerization Processes.

Novel bimetallic zinc acetate complexes supported by heteroscorpionate ligands have been developed for the ring-opening copolymerization of cyclohexene oxide and CO2 and the terpolymerization of cyclohexene oxide, phthalic anhydride, and CO2. Heteroscorpionate ligands precursors L1-L3 were reacted with two equivalents of zinc acetate to afford the dinuclear zinc complexes [{Zn(κ3-bpzappe)}(µ-O2CCH3)3-{Zn(HO2CCH3)}] (1), [{Zn(κ3-bpzbdmape)}(µ-O2CCH3)3-{Zn(HO2CCH3)}] (2), and [{Zn(κ3-bpzbdeape)}(µ-O2CCH3)3{Zn(HO2CCH3)}] (3) in excellent yields. The molecular structure of these compounds was determined spectroscopically and confirmed by X-ray diffraction analysis. Zinc acetate complexes 1-3 were screened as catalysts for the copolymerization of cyclohexene oxide and CO2 to produce poly(cyclohexene)carbonate, and complex 3 was found to be the most active catalyst for this process in the absence of a cocatalyst. Furthermore, the terpolymerization of cyclohexene oxide, phthalic anhydride, and CO2 was studied using the combination of complex 3 and 4-dimethylaminopyridine as catalyst system yielding the corresponding polyester-polycarbonate materials.

Efficient CO2 fixation into cyclic carbonates catalyzed by NNO-scorpionate zinc complexes.

A series of new chiral zwitterionic NNO-scorpionate mononuclear zinc alkyls [Zn(R)(κ3-NNO)]Br was developed in very high yields via suitable quaternization in the scorpionate ligand. These zwitterionic complexes performed as bifunctional catalysts and exhibited improved catalytic activity for the fixation of CO2 into cyclic carbonates compared to the neutral analog mononuclear [Zn(R)(κ3-NNO)] and binuclear [Zn(R)(κ2-NNµ-O)Zn(R)2] compounds. The catalyst system showed a broad substrate scope and functional group tolerance under mild and solvent-free conditions.

Synthesis of helical aluminium catalysts for cyclic carbonate formation.

Helical aluminium complexes [Al2X4(µ-nbptam)] (X = Me 1, Et 2), [Al2X4(µ-fbpam)] (R = Me 3, Et 4), [Al3X7(µ-nbptam)] (X = Me 5, Et 6) and [Al3X7(µ-fbpam)] (X = Me 7, Et 8) have been prepared by treatment of scorpionate ligand precursors with two or three equivalents of the corresponding trialkylaluminium derivative. The structures of these complexes have been determined by spectroscopic methods and the X-ray crystal structure of complex 1 has also been established. These complexes have been studied as catalysts for the chemical fixation of carbon dioxide into cyclic carbonates displaying good catalytic activity. When cyclohexene oxide was used as a substrate, polyether-polycarbonate was obtained in a ratio which is highly dependent on the cocatalyst and the catalyst to cocatalyst ratio used.

Influence of the Counterion on the Synthesis of Cyclic Carbonates Catalyzed by Bifunctional Aluminum Complexes.

New bifunctional aluminum complexes have been prepared with the aim of studying the effect of a counterion on the synthesis of cyclic carbonates from epoxides and carbon dioxide (CO2). Neutral ligand 1 was used as a precursor to obtain four novel mesylate, chloride, bromide, and iodide zwitterionic NNO ligands (2-5). The reaction of these ligands with 1 or 2 equiv of AlR3 (R = Me, Et) allowed the synthesis of mono- and bimetallic bifunctional aluminum complexes [AlR2(κ2-mbpzappe)]X [X = Cl, R = Me (6), Et (7); X = Br, R = Me (8), Et (9); X = I, R = Me (10), Et (11)] and [{AlR2(κ2-mbpzappe)}(µ-O){AlR3}]X [X = MeSO3, R = Me (12), Et (13); X = Cl, R = Me (14), Et (15); X = Br, R = Me (16), Et (17); X = I, R = Me (18), Et (19)] via alkane elimination. These complexes were studied as catalysts for the synthesis of cyclic carbonates from epoxides and CO2. Iodide complex 11 showed to be the most active catalyst for terminal epoxides, whereas bromide complex 9 was found to be the optimal catalyst when internal epoxides were used, showing the importance of the nucleophile cocatalyst on the catalytic activity.

Assessment of doxorubicin delivery devices based on tailored bare polycaprolactone against glioblastoma.

Bare polycaprolactones with controlled molar mass and dispersity were employed to manufacture biodegradable devices, which were applied for doxorubicin delivery in glioblastoma. Micro- and nanoscale devices were prepared by emulsion formation or by a combination of precipitation and hydrolysis. The carriers were characterized by scanning electron microscopy, dynamic light scattering techniques, thermogravimetric analysis and differential scanning calorimetry. The encapsulation parameters and drug-release profiles are discussed in order to evaluate the influence of different fundamental parameters, such as molar mass and dispersity value, pH, morphology or crystallinity, on the efficiency of the doxorubicin delivery systems. The ability of doxorubicin-loaded micro- and nanoscale devices to induce cellular toxicity in glioblastoma cells was also explored. A cell viability assay against C6 cells of doxorubicin-loaded nanocarriers showed higher cytotoxicity than doxorubicin-loaded microcarriers. In addition, doxorubicin-loaded nanocarriers also showed good antitumor profile in human tumoral cells and improved the security profile in relation to free doxorubicin in non-tumoral cells. Consistent with the assessment study described in this manuscript, the results provide a proof of concept for the suitability of the approach, based on bare polycaprolactone, to local controlled-sustained release of doxorubicin for the treatment of glioblastoma.

Study of the Coordination Modes of Hybrid NNCp Cyclopentadienyl/Scorpionate Ligands in Ir Compounds.

A new coordination mode for the hybrid scorpionate/cyclopentadienyl ligand bpzcp, [bpzcp = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1,1-diphenylethylcyclopentadienyl] is observed in iridium complexes. The reaction of the lithium precursor, [Li(bpzcp)(THF)], with a range of [IrCl(diene)]2 compounds leads to an unprecedented binding mode of the hybrid scorpionate/cyclopentadienyl ligand as η5-Cp-coordinated and the formation of Ir(I) derivatives [Ir(η5-Cp-bpzcp)(η4-cod)] (1), [Ir(η5-Cp-bpzcp){η4-CH2═C(Me)C(Me)═CH2}] (2), [Ir(η5-Cp-bpzcp)(η2-coe)2] (3), and [Ir(η5-Cp-bpzcp)(η2-CH2═CH2)2] (4). The Ir(I) complex 4 reacts with CO or bromine to afford the compound [Ir(η5-Cp-bpzcp)(CO)2] (5) and the 18e- Ir(III) complex [Ir(κ-N-η5-Cp-bpzcpBr2)Br2] (6), respectively. Reaction of the iridium compounds (2-4) with CuI or [PdCl2(CH3CN)2] yields the heterobimetallic iridium-copper or iridium-palladium complexes [Ir(η5-Cp-bpzcp){η4-CH2═C(Me)C(Me)═CH2}(µ-bpzcp){CuI(κ2-NN-bpzcp)}] (7), [Ir(η5-Cp-bpzcp)(η2-coe)2}(µ-bpzcp){CuI(κ2-NN-bpzcp)}] (8), [Ir(η5-Cp-bpzcp)(η2-CH2═CH2)2}(µ-bpzcp){CuI(κ2-NN-bpzcp)}] (9), [Ir(η5-Cp-bpzcp)(coe)2}(µ-bpzcp){PdCl2(κ2-NN-bpzcp)}] (10), and [Ir(η5-Cp-bpzcp)(η2-CH2═CH2)2(µ-bpzcp){PdCl2(κ2-NN-bpzcp)}] (11). All products were characterized by spectroscopic methods and the X-ray crystal structures of 1, 2, 3, 4, and 6 were also established.

Alternating Copolymerization of Epoxides and Anhydrides Catalyzed by Aluminum Complexes.

The optimization of an organoaluminum catalytic system for the copolymerization of epoxides and anhydrides is presented. For this purpose, the influence of different variables in the process, such as catalysts, cocatalyst, solvent, or substrates, has been analyzed. Kinetic studies, a proposal for the catalytic mechanism, and full characterization of the copolymers obtained are also discussed. Finally, a new copolymer, poly(limonene succinate), obtained by the optimized catalytic system is reported.

An Efficient and Versatile Lanthanum Heteroscorpionate Catalyst for Carbon Dioxide Fixation into Cyclic Carbonates.

A new lanthanum heteroscorpionate complex has shown exceptional catalytic activity for the synthesis of cyclic carbonates from epoxides and carbon dioxide. This catalyst system also promotes the reaction of bio-based epoxides to give an important class of bis(cyclic carbonates) that can be further used for the production of bio-derived non-isocyanate polyurethanes. The catalytic process requires low catalyst loading and mild reaction conditions for the synthesis of a wide range of cyclic carbonates.

One-Component Aluminum(heteroscorpionate) Catalysts for the Formation of Cyclic Carbonates from Epoxides and Carbon Dioxide.

New neutral and zwitterionic chiral NNO-donor scorpionate ligands 1 and 2 were designed to obtain new mononuclear and dinuclear NNO-heteroscorpionate aluminum complexes. Reaction of 1 with [AlR3 ] (R=Me, Et) in a 1:1 or 1:2 molar ratio afforded the neutral mononuclear alkyl complexes [AlR2 (κ2 -bpzappe)] {R=Me (3), Et (4); bpzappeH=2,2-bis(3,5-dimethylpyrazol-1-yl)-1-[4-(dimethylamino)phenyl]-1-phenylethanol} and bimetallic complexes [{AlR2 (κ2 -bpzappe)}(µ-O){AlR3 }] [R=Me (5), Et (6)]. By reaction of complexes 3-6 with PhCH2 Br, mononuclear and dinuclear cationic aluminum complexes [AlR2 (κ2 -bbpzappe)]Br {R=Me (7), Et (8); bbpzappeH=N-benzyl-4-[2,2-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1-hydroxy-1-phenylethyl]-N,N-dimethylbenzenaminium bromide} and [{AlR2 (κ2 -bbpzappe)}(µ-O){AlR3 }]Br [R=Me (9), Et (10)] were synthesized. Both neutral aluminum complexes in the presence of Bu4 NBr and cationic aluminum complexes were investigated as catalysts for cyclic carbonate formation from epoxides and carbon dioxide. Amongst them, complex 10 was found to be an efficient one-component catalyst for the synthesis of cyclic carbonates from both monosubstituted and internal epoxides and was shown to have broad substrate scope.