Benzyl Units Research Articles

N‐heterocyclic carbene complexes RuII(arene) and their application as ROMP catalysts, antioxidant and anticancer agents

N‐Heterocyclic carbenes (NHCs) play an important role in metal complex catalysis and stabilisation, providing stability under non‐inert conditions and a high σ‐donor capacity. They are crucial ligands for the synthesis of organometallic compounds like RuII‐complexes, which can operate as very active catalysts for a variety of chemical transformations and functionalizations. RA(Ruthenium‐arene)NHC complexes, known for their piano‐stool structure, stabilise Ru(II) oxidation by occupying three ruthenium coordination sites with a η6‐coordinated arene ligand. The development of dual‐acting RuII‐arene complexes has sparked increased interest in their catalytic and biological properties. Because of their broad spectrum, metal complexes can give distinct mechanisms of pharmacological action than organic drugs. This study aimed to explore the impact of ligand amphiphilicity and counterion on bioactivity, designing a family of compounds with the NHC ligand bearing an ester moiety and switching the wingtip substituent from methyl to benzyl units. All synthesized compounds were tested in norbornene ROMP, a benchmark reaction for RuII potential catalysts and as anticancer and antioxidant compounds.

Investigation of cholinesterase and α-glucosidase enzyme activities, and molecular docking and dft studies for 1,2-disubstituted cyclopentane derivatives with phenyl and benzyl units.

Six known products (4-9) were prepared from reaction of adipoyl chloride with 1,2,3-trimethoxybenzene according to the literature. From (2,3,4-trimethoxyphenyl)(2-(2,3,4-trimethoxyphenyl)cyclopent-1-en-1-yl)methanone (4) of them, four new 1,2-disubstituted cyclopentane derivatives (10-13) with phenyl and benzyl units were synthesized by reactions such as hydrazonation, catalytic hydrogenation and bromination. The obtained compounds 4-13 were examined for their in vitro inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. All compounds 4-13 showed inhibition at nanomolar level with Ki values in the range of 45.53 ± 7.35-631.96 ± 18.88nM for AChE, 84.30 ± 9.92-622.10 ± 35.14nM for BChE, and 25.47 ± 4.46-48.87 ± 7.33 for α-Glu. In silico molecular docking studies of the potent compounds were performed in the active sites of AChE (PDB: 1E66), BChE (PDB: 1P0I), and α-glucosidase (PDB: 5ZCC) to compare the effect of bromine atom on the inhibition mechanism. The optimized molecular structures, HOMO-LUMO energies and molecular electrostatic potential maps for the compounds were calculated by using density functional theory with B3LYP/6-31 + G(d,p).

Chiroptical Properties of a Cryptophane Soluble at Neutral pH

AbstractThis article reports the synthesis of the two enantiomers of a water‐soluble cryptophane 3 enabling cesium and thallium complexation at neutral or basic pH. The two enantiomers of 3 were obtained in a two steps synthesis from cryptophane 4, a molecule decorated with three phenol groups and three other phenol groups protected by benzyl units. The two enantiomers of 4 were isolated from liquid chromatography using chiral stationary phase. The absolute configuration of the two enantiomers of 3 was determined by vibrational circular dichroism combined with theoretical calculations. Contrary to cryptophane 1 that present large spectroscopic changes upon cesium and thallium complexation, the electronic circular dichroism spectra of compound 3 exhibit moderate spectral changes suggesting that this compound cannot change the conformation of its linkers as easily as cryptophane 1.

Synthesis, Theoretical, in Silico and in Vitro Biological Evaluation Studies of New Thiosemicarbazones as Enzyme Inhibitors.

Eleven new thiosemicarbazone derivatives (1-11) were designed from nine different biologically and pharmacologically important isothiocyanate derivatives containing functional groups such as fluorine, chlorine, methoxy, methyl, and nitro at various positions of the phenyl ring, in addition to the benzyl unit in the molecular skeletal structure. First, their substituted-thiosemicarbazide derivatives were synthesized from the treatment of isothiocyanate with hydrazine to synthesize the designed compounds. Through a one-step easy synthesis and an eco-friendly process, the designed compounds were synthesized with yields of up to 95 % from the treatment of the thiosemicarbazides with aldehyde derivatives having methoxy and hydroxy groups. The structures of the synthesized molecules were elucidated with elemental analysis and FT-IR, 1 H-NMR, and 13 C-NMR spectroscopic methods. The electronic and spectroscopic properties of the compounds were determined by the DFT calculations performed at the B3LYP/6-311++G(2d,2p) level of theory, and the experimental findings were supported. The effects of some global reactivity parameters and nucleophilic-electrophilic attack abilities of the compounds on the enzyme inhibition properties were also investigated. They exhibited a highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (KI values are in the range of 23.54±4.34 to 185.90±26.16 nM, 103.90±23.49 to 325.90±77.99 nM, and 86.15±18.58 to 287.70±43.09 nM for AChE, hCA I, and hCA II, respectively). Furthermore, molecular docking simulations were performed to explain each enzyme-ligand complex's interaction.

Design of Statistical Copolypeptides as Multipurpose Hydrogel Resins in 3D Printing

AbstractHydrogels possess desirable properties for the additive manufacturing of 3D objects, but a significant challenge is to expand the range of hydrogel feedstocks with defined molecular structure and functionality while retaining mechanical properties. To this end, the design of photopolymerizable copolypeptides, derived from linear or star‐shaped architectures which can be tailored to provide control over mechanical properties and associated 3D printing performance, are reported. Based on hydroxy ethyl‐L‐glutamine and vinylbenzyl‐L‐cysteine residues, physical crosslinking via β‐motif assembly is shown to afford hydrogels with viscoelastic properties that allow their use as resins for direct ink writing (DIW) and/or direct laser writing (DLW). The strategic incorporation of vinyl benzyl units permits rapid photocrosslinking of the self‐assembled hydrogels leading to mechanically robust 3D objects. Significantly, copolypeptide architecture directly influences hydrogel resin viscosity, which affords materials with tailorable characteristics for different 3D printing techniques, highlighting the intrinsic versatility of these systems.

Effect of disubstitution pattern of the terminal alkyl chains on the mesophase of liquid crystals based on lanthanide(III) complexes: A study of the thermal, emission and dielectric behavior

In the present work, new luminescent lanthanide complexes with extended mesomorphic range were prepared by coordination to lanthanide ions (Eu3+, Sm3+ and Tb3+) of the new 4-pyridone based organic ligands (L) with 3,4- (7-n) and 3,5-di(alkyloxy)benzyl (8-n) mesogenic groups and variable length (n = 12 or 14 carbon atoms) onto the benzyl unit. The cumulative results of the elemental analyses as well as the 1H, 13C NMR and IR spectroscopies support the structure of the organic derivatives and their lanthanide complexes [LnL3(NO3)3] (9-n/Ln and 10-n/Ln) described in this work. These complexes show characteristic lanthanide solid state emission, both at room and elevated temperatures corresponding to crystalline, glassy or liquid crystal states. The long range SmA phases displayed by all complexes were supported by a combination of characterization methods, including: differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and variable-temperature powder X-ray diffraction (XRD). This work shows that the number, substitution pattern and length of flexible alkoxy chains are important parameters to control the phase-transition characteristics of the lanthanide complexes. Complexes with 3,4-disubstituted pattern (9-n/Ln) show higher clearing temperatures (nearly 60 °C for Eu3+, 70 °C for Sm3+ and 85 °C for Tb3+ complexes) compared to their counterparts with 3,5-disubstituted pattern (10-n/Ln). Moreover, complexes 9-n/Ln crystallize when cooling their LC phase while complexes 10-n/Ln are stable in glassy state at room temperature as a consequence of the different close interdigitated molecular packing evidenced by XRD measurements. Dielectric spectroscopy was employed to detect the changes of order degree specific to each phases (crystalline, LC or isotropic). The variation of dielectric constant and the electrical conductivity versus temperature shows three transition intervals for selected complexes 10-14/Sm and 10-14/Tb, which delimit the main intervals: 45–60 °C, 90–110 °C; 140–160 °C corresponding to the Cr1-Cr2, Cr2 – SmA and SmA-Iso transitions, and agree very well with the DSC results. The change of characteristic time, obtained by Havriliak-Negami fit function, with temperature also provides a very good correlation with the DSC and POM results.

Effect of Substituent of Roof Shape Amines on the Molecular Recognition of Optically Active Acids by NMR Spectroscopy

AbstractOptically active roof shape derivatives of benzyl amines were synthesized and screened as chiral solvating agents for the study of molecular recognition of chiral compounds by NMR and UV spectroscopy. The effect of substituents on the aromatic ring of benzyl unit is investigated to assess the binding ability with the analyte and an experimental correlation is observed. Altering the substituents on the ring of benzyl amine and the acidic substrates, significantly influence the CSA interactions. The supramolecular interactions between acid and amine in the single crystal X‐ray analysis of the diastereomeric salts provide further insight of the mode of molecular recognition.

Synthesis and thermal, emission and dielectric properties of liquid crystalline Eu(III), Sm(III) and Tb(III) complexes based on mesogenic 4-pyridone ligands functionalized with cyanobiphenyl groups

New thermotropic lanthanidomesogens based on Eu(III), Sm(III) and Tb(III) with N-alkylated 4-pyridones mesogenic ligands, having two cyanobiphenyl groups attached via long alkoxy spacers, with 6, 9 and 10 carbons atoms in 3,5 - positions of a benzyl unit, have been designed and investigated. The liquid crystal behavior was assessed by differential scanning calorimetry, the mesophases being assigned by polarized light microscopy based on their characteristic textures and confirmed by variable temperature X-ray powder diffraction analysis. The three N-alkylated 4-pyridones nematic ligands reacted with lanthanide nitrates to yield new lanthanidomesogens with a stable and reproducible smectic A phase up to 125°C. The emission spectra of the complexes have shown the characteristic emission of the lanthanide trivalent ions, over the entire temperature range of SmA phase up to isotropic state. The dielectric spectroscopy measurements performed in the temperature range of existence of the liquid crystal phase, both in the low frequency (LF) domain 0.01–10MHz and in the high frequency (HF) range, 1MHz–3GHz, revealed three dipolar relaxation processes. The characteristic times have been obtained by fitting the spectra of the dielectric loss with a two component Havriliak-Negami function. The activation constant/energy was determined from the Vogel-Fülcher-Tammann law.

Bright perovskite light-emitting diodes with improved film morphology and reduced trap density via surface passivation using quaternary ammonium salts

Abstract Organic-inorganic hybrid perovskite light-emitting diodes (PeLEDs) have emerged as one of the promising candidates for display and illumination devices with low-cost and high color purity. However, PeLEDs exhibit bad film uniformity and high defect density, which lead to poor device performance. Herein, we introduce an additive engineering strategy employing quaternary ammonium salts, namely benzyltrimethylammonium bromide (BTABr), phenyltrimethylammonium bromide (PTABr) and benzyltrimethylammonium chloride (BTACl), in the precursor solution to prepare uniform and dense MAPbBr3 perovskite films with reduced grain sizes. These quaternary ammonium salts, which have cations containing a bulky benzyl unit, are more effective at reducing the grain sizes of MAPbBr3 perovskites. More importantly, the BTABr additive performs a dual-passivation effect to the MAPbBr3, effectively reducing the trap density within the perovskite layer as well as the proportion of non-radiative recombination of PeLEDs, and balancing the charge injection. Consequently, PeLEDs incorporating a BTABr-modified MAPbBr3 layer exhibit a reduced turn-on voltage from 4.2 to 2.6 V, and the maximum luminance and current efficiency are enhanced from 3490 Cd/m2 and 0.24 Cd/A of the reference device to 12026 Cd/m2 and 1.27 Cd/A, respectively.

Aromatic C\u2013H\u22ef\u03c0, C\u2013H\u22efO and parallel aromatic\u2013aromatic interactions in the crystal structure of meso-tetrakis[4-(benzyloxy)phenyl]porphyrin

Analysis of the crystal packing of the title porphyrin derivative (C72H54N4O4) suggests no classical hydrogen bonds between neighbor molecules. X-ray crystal structure shows that all benzyl units of this porphyrin have close C–H⋯π weak contacts with phenyl or porphyrinyl units forming a network of porphyrin rings. Also C–H⋯O and parallel aromatic–aromatic weak interactions play an important role in structure extension. All of these interactions control the crystal packing of molecules. X-ray diffraction was used to perform single crystal analysis. The structure was solved in the triclinic space group P-1, with unit cell parameters: a = 8.0597(3) Å, b = 11.6862(4) Å, c = 14.2572(5) Å, α = 96.173(3)°, β = 93.150(4)°, and γ = 93.679(3)°, V = 1329.72(8) Å3, Z = 1.Graphical abstractThe lack of strong intermolecular hydrogen bonds and presence of numerous weak hydrogen bonds are decisive factors in crystal structure of the examined meso-tetrakis[4-(benzyloxy)-phenyl]porphyrin.

Nickel-catalysed carbonylative homologation of aryl iodides

Homologation is an important organic transformation which extends the carbon chain of a parent molecule, and many procedures have been established. However, although carbonylation reactions are now well developed as valuable methods for the synthesis of carbonyl-containing compounds, studies of carbonylative homologation are limited. Here we report a nickel-catalysed carbonylative homologation of aryl iodides. With molybdenum hexacarbonyl as the solid carbon monoxide source and silane as the deoxygenation reagent, benzylic units can be effectively produced. Various (hetero)arenes can be successfully benzylated and give the corresponding products in moderate to excellent yields.

Synthesis and crystal structure of an M4L6 tetrahedral cage with outward-facing pockets from a substituted pyrazolyl-pyridine ligand.

The self-assembly of metal-polydentate ligands to give supramolecular tetrahedral complexes is of considerable current interest. A new ligand, 4-benzyl-2-[1-(2-{[3-(4-benzylpyridin-2-yl)-1H-pyrazol-1-yl]methyl}benzyl)-1H-pyrazol-3-yl]pyridine (L), with chelating pyrazolyl-pyridine units substituted on the 4-position of the pyridyl ring with benzyl units, has been synthesized and fully characterized. The self-assembly of L with cobalt(II) gave rise to a tetrahedral cage (hexakis{μ-4-benzyl-2-[1-(2-{[3-(4-benzylpyridin-2-yl)-1H-pyrazol-1-yl]methyl}benzyl)-1H-pyrazol-3-yl]pyridine}perchloratotetracobalt(II) octakis(perchlorate) acetonitrile undecasolvate, [Co4(ClO4)(C38H32N6)6](ClO4)7·11CH3CN) with approximate T symmetry. The X-ray crystal structure of the cage, i.e. [Co4L6-ClO4](ClO4)7, shows that the substituted benzyl groups are oriented away from the centres of their respective ligands towards the CoII vertices, making small outward-facing pockets from three benzyl rings at the corners of the tetrahedron.

2:2 Complexes from Diphenylpyridiniums and Cucurbit[8]uril: Encapsulation‐Promoted Dimerization of Electrostatically Repulsing Pyridiniums

Rigid linear compounds G1 and G2, which contained two 4-phenylpyridinium (PhPy+ ) units, have been prepared to investigate their binding with cucurbit[8]uril (CB[8]). X-ray crystallographic structures revealed that in the solid state both compounds were included by CB[8], through antiparallel stacking, to form 2:2 quaternary complexes (G1)2 @(CB[8])2 and (G2)2 @(CB[8])2 . For the former complex, CB[8] entrapped G1 by holding two heterodimers of its Py+ and benzyl units, which were at opposite ends of the backbone. In contrast, for the first time, the second complex disclosed parallel stacking of two cationic Py+ units of G2 in the cavity of CB[8] in the solid state, despite the generation of important electrostatic repulsion. Isothermal titrations in water afforded high apparent association constants of 4.36×106 and 6.43×106 m-1 for 1:1 complexes G1@CB[8] and G2@CB[8], respectively, and 1 H NMR spectroscopy experiments in D2 O confirmed a similar stacking pattern to that observed in the solid state. A previous study and crystal structures of the 2:1 complexes formed between three new controls, G3-5, and CB[8] did not display such unusual stacking of the cationic Py+ unit; this may be attributed to the multivalency of the two CB[8] encapsulation interactions.

Dual-mode cross-coupling on aromatic imino compounds by dihydridoruthenium catalysts

In the catalytic cross-coupling reaction of ketimines, derived from 1-acetonaphthone or acetophenone derivatives and benzylamine, with trialkoxyvinylsilanes RuH2(PPh3)4 or RuH2(CO)(PPh3)3 catalyst caused the selective alkenylation and alkylation on each aromatic ring of the ketimines separately (i.e. dual-mode coupling). Alkenylation occurred at the ortho-position(s) of the benzyl unit and alkylation occurred at the ortho-position(s) of 1-arylethylidene moiety of the substrates. By the stoichiometric reaction of N-1-(4-methylphenyl)ethylidene-4-methylbenzylamine with RuH2(CO)(PPh3)3 in the presence of three equivalents of vinylsilane, a novel ruthenium bismetallacylclic complex with two ruthenium-carbon bonds was isolated. This (C,N,C)-bismetallacycle complex was converted to the alkenylated complex by the reaction with two equiv. of vinylsilane. These observations indicate that the dual-mode coupling proceeds in a sequence of alkenylation followed by alkylation via intermediary bismetallacyclic complex formation.

Photocatalytic Oxygen Evolution from Functional Triazine-Based Polymers with Tunable Band Structures.

Conjugated polymers (CPs) are emerging and appealing light harvesters for photocatalytic water splitting owing to their adjustable band gap and facile processing. Herein, we report an advanced mild synthesis of three conjugated triazine-based polymers (CTPs) with different chain lengths by increasing the quantity of electron-donating benzyl units in the backbone. Varying the chain length of the CTPs modulates their electronic, optical, and redox properties, resulting in an enhanced performance for photocatalytic oxygen evolution, which is the more challenging half-reaction of water splitting owing to the sluggish reaction kinetics. Our results could stimulate interest in these functional polymers where a molecular engineering strategy enables the production of suitable semiconductor redox energetics for oxygenic photosynthesis.

Two new algal bromophenols from Odonthalia corymbifera

Two new algal bromophenols, odonthalol and odonthadione, were isolated from the alga Odonthalia corymbifera. Odonthalol was determined as a trimer of brominated hydroxylated benzyl (BHB) units. Three units were connected via ether and methylene bridges. Odonthadione was identified as a hybrid compound of the BHB unit and a unique cyclopentenedione. The cyclopentenedione unit has not been reported from natural origin.

Compartmentalization Technologies via Self-Assembly and Cross-Linking of Amphiphilic Random Block Copolymers in Water.

Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random block copolymers in water afforded an approach to tailor-make well-defined compartments and domains in single polymer chains and nanoaggregates. For a double compartment single-chain polymer, an amphiphilic random block copolymer bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl, and olefin pendants was synthesized by living radical polymerization (LRP) and postfunctionalization; the dodecyl and benzyl units were incorporated into the different block segments, whereas PEG pendants were statistically attached along a chain. The copolymer self-folded via the orthogonal self-assembly of hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular cross-linking, to form a single-chain polymer carrying double yet distinct hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine terminal served as a globular macroinitiator for LRP to provide an amphiphilic tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic polymer tail; the tadpole thus self-assembled into multicompartment aggregates in water.

Photochemically Assisted Introduction of a Benzyl Unit into Isoquinolines Using Benzyltrifluoroborates

Isoquinoline was photochemically benzylated at its 1 position with benzyltrifluoroborate reagents in the presence of methyl chloroformate. When a benzyl group substituted by an electron-donating group was employed, the benzylation thermally proceeded. The present reaction allowed straightforward synthesis of the skeleton for the benzylisoquinoline alkaloid.

Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

The alkylation of one of the nitrogen atoms of the molecule 1,3,5,triaza‐7‐phosphaadamantane (PTA) with para‐substituted benzylic units and the l‐phenylalanine methyl ester moiety are reported. The crystalline structures of the two alkylated PTA species [PTA‐CH2‐p‐COOH‐C6H4]Br (1a) and [PTA‐CH2‐p‐CH2COOH‐C6H4]Br (2) reveal the presence of interactions between the bromide anion and the OH group of the acid moiety. Bis‐phosphane derivatives were prepared by the alkylation of two PTA molecules with a dibromide salt to afford more water‐soluble species. The corresponding mono‐ and dinuclear chloro‐, thiocyanato‐ and pentafluorophenyl gold(I) derivatives are described. Most of the new complexes have been tested as anticancer agents, exhibiting higher cytotoxicity than cisplatin against human colon cancer cell lines. Some of them display low cytotoxicity towards differentiated cells (non‐carcinogenic), as determined from viability studies, thereby demonstrating a significant specificity in this type of cancer.

Macrocyclic Se4N2[7,7]ferrocenophane and Se2N[10]ferrocenophane containing benzyl unit: synthesis, complexation, crystal structures, electrochemical and optical properties.

Two novel macrocyclic polyselena[n]ferrocenophanes containing a pendent benzyl unit, 20-membered Se4N2[7,7]ferrocenophane (L1) and 10-membered Se2N[10]ferrocenophane (L2), were designed and synthesized. The reaction of L1 with two molar amounts of metal salts (M = Cu(+), Cu(2+), Pd(2+) and Hg(2+)) led to six dimetallic complexes 1-6. A crystallographic study revealed that each metal center in 1-5 was tetracoordinated to two selenium atoms from different ferrocene units, one aliphatic nitrogen atom and one co-ligand. The structures of the complexes contain a two-fold axis perpendicular to the molecular plane with two pendant benzyl moieties in an anti-conformation. Macrocycle L1 gives significant electrochemical, linear and third-order nonlinear optical responses to Cu(2+) and Hg(2+). The DFT/B3LYP calculations of 4 demonstrated a small HOMO-LUMO energy gap and delocalization of the π-electron cloud in the frontier molecular orbitals, which led to the enhancement of molecular NLO properties after complexation. The results show that the oxidation state of the ferrocene unit is accompanied by significant differences in the corresponding absorption spectra and third-order NLO properties.