Altering the structures of 3D supramolecular assemblies from melamine and cyanuric acid derivatives in water.

Herein, we obtained two supramolecular assemblies with layered structures from melamine, N-methylmelamine, and hexynyl-cyanuric acid in water. By combination of X-ray diffraction, electron microscopy, and molecular dynamics studies, we found that introducing one methyl group in melamine alters the arrangement of the layers in these structures.

Observation of a chemical reaction in a levitating microdroplet cluster and droplet-generated music.

Ordered clusters of water droplets levitating over a heated water surface can be used as chemical microreactors and computational devices. Here we show that a chemical reaction between melamine and cyanuric acid can occur during coalescence of pairs of droplets containing these reagents and lead to the sedimentation of the product, crystals of melamine cyanurate. In rotating droplets, the crystals flash with frequencies dependent mostly on the rotational velocity of the droplets defined by the rotor of the velocity field of the air-vapor flow above the heated water surface. With the Machine Learning (ML) approach, we trace the brightness and frequencies of individual crystals and convert the frequencies into musical notes thus making a "micro-orchestra" of the levitation cluster.

Calix[4]arene-pyrazole conjugates as potential cancer therapeutics.

Tumor selectivity is yet a challenge in chemotherapy-based cancer treatment. A series of calixarenes derivatized at the lower rim with 3-phenyl-1H-pyrazole units with variable upper-rim substituent and conformations of macrocyclic core, alkyl chain length between heterocycle and core, as well as phenolic monomer (5-(4-tert-butylphenyloxy)methoxy-3-phenyl-1H-pyrazole) have been synthesized and characterized in a range of therapeutically relevant cellular models (M-HeLa, MCF7, A-549, PC3, Chang liver, and Wi38) from different target organs/systems. Specific cytotoxicity for M-HeLa cells has been observed in tert-butylcalix[4]arene pyrazoles in 1,3-alternate (compound 7b) and partial cone (compound 7c) conformations with low mutagenicity and haemotoxicity and in vivo toxicity in mice. Compounds 7b,c have induced mitochondrial pathway of apoptosis of M-HeLa cells through caspase-9 activation preceded by the cell cycle arrest at G0/G1 phase. A concomitant overexpression of DNA damage markers in pyrazole-treated M-HeLa cells suggests that calixarene pyrazoles target DNA, which was supported by the presence of interactions between calixarenes and ctDNA at the air-water interface.

Uricase Crowding via Polyelectrolyte Layers Coacervation for Carbon Fiber-Based Electrochemical Detection of Uric Acid.

Urate oxidase (UOx) surrounded by synthetic macromolecules, such as polyethyleneimine (PEI), poly(allylamine hydrochloride) (PAH), and poly(sodium 4-styrenesulfonate) (PSS) is a convenient model of redox-active biomacromolecules in a crowded environment and could display high enzymatic activity towards uric acid, an important marker of COVID-19 patients. In this work, the carbon fiber electrode was modified with Prussian blue (PB) redox mediator, UOx layer, and a layer-by-layer assembled polyelectrolyte film, which forms a complex coacervate consisting of a weakly charged polyelectrolyte (PEI or PAH) and a highly charged one (PSS). The film deposition process was controlled by cyclic voltammetry and scanning electron microscopy coupled with energy-dispersive X-ray analysis (at the stage of PB deposition) and through quartz crystal microbalance technique (at latter stages) revealed uniform distribution of the polyelectrolyte layers. Variation of the polyelectrolyte film composition derived the following statements. (1) There is a linear correlation between electrochemical signal and concentration of uric acid in the range of 10-4-10-6 M. (2) An increase in the number of polyelectrolyte layers provides more reproducible values for uric acid concentration in real urine samples of SARS-CoV-2 patients measured by electrochemical enzyme assay, which are comparable to those of spectrophotometric assay. (3) The PAH/UOx/PSS/(PAH/PSS)2-coated carbon fiber electrode displays the highest sensitivity towards uric acid. (4) There is a high enzyme activity of UOx immobilized into the hydrogel nanolayer (values of the Michaelis-Menten constant are up to 2 µM) and, consequently, high affinity to uric acid.

Piezo-Responsive Hydrogen-Bonded Frameworks Based on Vanillin-Barbiturate Conjugates.

A concept of piezo-responsive hydrogen-bonded π-π-stacked organic frameworks made from Knoevenagel-condensed vanillin-barbiturate conjugates was proposed. Replacement of the substituent at the ether oxygen atom of the vanillin moiety from methyl (compound 3a) to ethyl (compound 3b) changed the appearance of the products from rigid rods to porous structures according to optical microscopy and scanning electron microscopy (SEM), and led to a decrease in the degree of crystallinity of corresponding powders according to X-ray diffractometry (XRD). Quantum chemical calculations of possible dimer models of vanillin-barbiturate conjugates using density functional theory (DFT) revealed that π-π stacking between aryl rings of the vanillin moiety stabilized the dimer to a greater extent than hydrogen bonding between carbonyl oxygen atoms and amide hydrogen atoms. According to piezoresponse force microscopy (PFM), there was a notable decrease in the vertical piezo-coefficient upon transition from rigid rods of compound 3a to irregular-shaped aggregates of compound 3b (average values of d33 coefficient corresponded to 2.74 ± 0.54 pm/V and 0.57 ± 0.11 pm/V), which is comparable to that of lithium niobate (d33 coefficient was 7 pm/V).

Thermodynamic vs. Kinetic Control in Synthesis of O-Donor 2,5-Substituted Furan and 3,5-Substituted Pyrazole from Heteropropargyl Precursor.

Elaboration of a convenient route towards donor-substituted pyrazoles from heteropropargyl precursors is challenging due to a number of thermodynamically favorable side reactions (e.g., acetylene-allene isomerization and Glaser homocoupling). In this work, Sonogashira cross-coupling conditions of 4-tert-butylphenyl propargyl ether with benzoyl chloride followed by tandem Michael addition/cyclocondensation with hydrazine into 3,5-disubstituted pyrazole (kinetic control), as well as cycloisomerization conditions of ketoacetylene intermediate into 2,5-disubstituted furan (thermodynamic control), were established through a variation of the catalyst loading, solvent polarity, excess of triethylamine, and time of reaction. During the optimization of process parameters, a number of by-products represented by a monophosphine binuclear complex (PPh3PdI2)2 with two bridging iodine atoms and diyne were identified and isolated in the pure form. The quantum-chemical calculations and solution-state 1H/13C NMR spectroscopy suggested that the 5(3)-(4-tert-butylphenyloxy)methoxy-3(5)-phenyl-1H-pyrazole exists in the tautomeric equilibrium in a polar methanol solvent and that individual tautomers could be characterized in case aprotic solvents employed. The pyrazole features a unique tetramer motif in the crystal phase formed by alternating 3(5)-phenyl-1H-pyrazole tautomers, which was stabilized by N-H···N bonds and stacking interactions of pyrazole rings, whereas pyrazole dimers were identified in the gas phase.

Thiacalixarenes with Sulfur Functionalities at Lower Rim: Heavy Metal Ion Binding in Solution and 2D-Confined Space.

Sulfur-containing groups preorganized on macrocyclic scaffolds are well suited for liquid-phase complexation of soft metal ions; however, their binding potential was not extensively studied at the air-water interface, and the effect of thioether topology on metal ion binding mechanisms under various conditions was not considered. Herein, we report the interface receptor characteristics of topologically varied thiacalixarene thioethers (linear bis-(methylthio)ethoxy derivative L2, O2S2-thiacrown-ether L3, and O2S2-bridged thiacalixtube L4). The study was conducted in bulk liquid phase and Langmuir monolayers. For all compounds, the highest liquid-phase extraction selectivity was revealed for Ag+ and Hg2+ ions vs. other soft metal ions. In thioether L2 and thiacalixtube L4, metal ion binding was evidenced by a blue shift of the band at 303 nm (for Ag+ species) and the appearance of ligand-to-metal charge transfer bands at 330-340 nm (for Hg2+ species). Theoretical calculations for thioether L2 and its Ag and Hg complexes are consistent with experimental data of UV/Vis, nuclear magnetic resonance (NMR) spectroscopy, and single-crystal X-ray diffractometry of Ag-thioether L2 complexes and Hg-thiacalixtube L4 complex for the case of coordination around the metal center involving two alkyl sulfide groups (Hg2+) or sulfur atoms on the lower rim and bridging unit (Ag+). In thiacrown L3, Ag and Hg binding by alkyl sulfide groups was suggested from changes in NMR spectra upon the addition of corresponding salts. In spite of the low ability of the thioethers to form stable Langmuir monolayers on deionized water, one might argue that the monolayers significantly expand in the presence of Hg salts in the water subphase. Hg2+ ion uptake by the Langmuir-Blodgett (LB) films of ligand L3 was proved by X-ray photoelectron spectroscopy (XPS). Together, these results demonstrate the potential of sulfide groups on the calixarene platform as receptor unit towards Hg2+ ions, which could be useful in the development of Hg2+-selective water purification systems or thin-film sensor devices.

Periodic Self-Assembly of Poly(ethyleneimine)-poly(4-styrenesulfonate) Complex Coacervate Membranes.

Coacervation is a self-assembly strategy based on the complexation of polyelectrolytes, which is utilized in biomedicine and agriculture, as well as automotive and textile industries. In this paper, we developed a new approach to the on-demand periodic formation of polyelectrolyte complexes through a Liesegang-type hierarchical organization. Adjustment of reaction conditions allows us to assemble materials with a tunable spatiotemporal geometry and establish materials' production cycles with a regulated periodicity. The proposed methodology allows the membrane to self-assemble when striving to reach balance and self-heal after exposure to external stimuli, such as potential difference and high pH. Using chronopotentiometry, K+ ion permeability behavior of the PEI-PSS coacervate membranes was demonstrated. The periodically self-assembled polyelectrolyte nanomembranes could further be integrated into novel energy storage devices and intelligent biocompatible membranes for bionics, soft nanorobotics, biosensing, and biocomputing.

Switching Ion Binding Selectivity of Thiacalix[4]arene Monocrowns at Liquid-Liquid and 2D-Confined Interfaces.

Understanding the interaction of ions with organic receptors in confined space is of fundamental importance and could advance nanoelectronics and sensor design. In this work, metal ion complexation of conformationally varied thiacalix[4]monocrowns bearing lower-rim hydroxy (type I), dodecyloxy (type II), or methoxy (type III) fragments was evaluated. At the liquid-liquid interface, alkylated thiacalixcrowns-5(6) selectively extract alkali metal ions according to the induced-fit concept, whereas crown-4 receptors were ineffective due to distortion of the crown-ether cavity, as predicted by quantum-chemical calculations. In type-I ligands, alkali-metal ion extraction by the solvent-accessible crown-ether cavity was prevented, which resulted in competitive Ag+ extraction by sulfide bridges. Surprisingly, amphiphilic type-I/II conjugates moderately extracted other metal ions, which was attributed to calixarene aggregation in salt aqueous phase and supported by dynamic light scattering measurements. Cation-monolayer interactions at the air-water interface were monitored by surface pressure/potential measurements and UV/visible reflection-absorption spectroscopy. Topology-varied selectivity was evidenced, towards Sr2+ (crown-4), K+ (crown-5), and Ag+ (crown-6) in type-I receptors and Na+ (crown-4), Ca2+ (crown-5), and Cs+ (crown-6) in type-II receptors. Nuclear magnetic resonance and electronic absorption spectroscopy revealed exocyclic coordination in type-I ligands and cation-π interactions in type-II ligands.

Thermally Stable Nitrothiacalixarene Chromophores: Conformational Study and Aggregation Behavior.

Achieving high thermal stability and control of supramolecular organization of functional dyes in sensors and nonlinear optics remains a demanding task. This study was aimed at the evaluation of thermal behavior and Langmuir monolayer characteristics of topologically varied nitrothiacalixarene multichromophores and phenol monomers. A nitration/azo coupling alkylation synthetic route towards partially O-substituted nitrothiacalixarenes and 4-nitrophenylazo-thiacalixarenes was proposed and realized. Nuclear magnetic resonance (NMR) spectroscopy and X-ray diffractometry of disubstituted nitrothiacalix[4]arene revealed a rare 1,2-alternate conformation. A synchronous thermal analysis indicated higher decomposition temperatures of nitrothiacalixarene macrocycles as compared with monomers. Through surface pressure/potential-molecular area measurements, nitrothiacalixarenes were shown to form Langmuir monolayers at the air-water interface and, through atomic force microscopy (AFM) technique, Langmuir-Blodgett (LB) films on solid substrates. Reflection-absorption spectroscopy of monolayers and electronic absorption spectroscopy of LB films of nitrothiacalixarenes recorded a red-shifted band (290 nm) with a transition from chloroform, indicative of solvatochromism. Additionally, shoulder band at 360 nm was attributed to aggregation and supported by gas-phase density functional theory (DFT) calculations and dynamic light scattering (DLS) analysis in chloroform-methanol solvent in the case of monoalkylated calixarene 3. Excellent thermal stability and monolayer formation of nitrothiacalixarenes suggest their potential as functional dyes.

Calixarene alpha-ketoacetylenes: versatile platforms for reaction with hydrazine nucleophile.

Late stage diversification of calix[4]arenes and thiacalix[4]arenes with heterocycles remains a significant synthetic challenge and hampers further exploitation of the scaffolds. Here we describe the development of a short and facile synthetic route to conformationally diverse novel calix[4]arene and thiacalix[4]arene ynones using a palladium cross coupling approach (5% Pd(ii) + 10% Cu(i)) with benzoyl chloride. Their successful conversion to heterocycles to afford pyrazoles was demonstrated through treatment with hydrazine. Functionalisation is calixarene conformation and linker independent enabling access to a library of structures.