Search Results (50)

Reverse micelles (RMs) are versatile nanostructures traditionally formed in low-polarity organic solvents, but the need for greener alternatives has limited their broader applicability. Here, we demonstrate for the first time that a hydrophobic Natural Deep Eutectic Solvent (NADES), prepared from a simple 1:1 mixture of camphor and menthol (CM), can act as the continuous external phase for RM formation. Remarkably, CM dissolves the benchmark surfactant sodium dioctyl sulfosuccinate (AOT) at concentrations up to 0.5 M without co-surfactants and supports water solubilization up to W₀ = [H₂O]/[AOT] = 5, yielding thermodynamically stable systems. 1H and DOSY NMR analyses reveal clear structural rearrangements of the micellar interface, confirm the encapsulation of water in the polar core, and provide quantitative evidence of size modulation as a function of W₀. The resulting CM/AOT/water assemblies represent the first example of NADES-based reverse micelles, offering an easily prepared, sustainable, and biocompatible platform. This breakthrough opens new perspectives for the development of green self-assembled systems with promising applications in areas such as food technology, pharmaceuticals, and nanomedicine. Full article

The cationic chloro-P-{[4-(diphenylphosphanyl)phenyl]-N,N-dimethylmethanammonio(norbornadiene)rhodium(I) complex was encapsulated inside a self-assembled hexameric capsule. This capsule was obtained through a reaction involving 2,8,14,20-tetra-undecyl-resorcin[4]arene and water in chloroform. The formation of an inclusion complex was deduced from a combination of spectral measurements (UV-visible spectroscopy, ¹H, ³¹P{¹H} NMR and DOSY). The rhodium complex was evaluated in the [2+2+2] cycloaddition between N,N-dipropargyl-p-toluenesulfonamide and arylacetylene derivatives. In the presence of two equivalents of arylacetylenes in water-saturated chloroform at 60 °C for 24 h, the 4-methyl-N-(prop-2-yn-1-yl)-N-((2-tosylisoindolin-5-yl)methyl)benzenesulfonamide, the homocycloaddition product of 1,6-diyne is predominantly formed. In the presence of the supramolecular capsule, a selectivity inversion in favor of 5-aryl-2-tosylisoindoline is observed, with heterocycloaddition products formed in proportions between 53 and 69%. Full article

The [PdCl₂(cod)] complex was encapsulated inside a self-assembled hexameric capsule obtained via a reaction of 2,8,14,20-tetra-undecyl-resorcin[4]arene and water. The formation of an inclusion complex was deduced from a combination of spectral measurements (UV-visible, ¹H NMR and DOSY spectroscopies). The latter proved effective in the dimerization of styrene derivatives under mild conditions, with a catalyst loading of 0.5 mol% at 60 °C. Electronically enriched vinyl arenes underwent cyclization of the catalytic products, leading to the quasi-quantitative formation of indanes from 4-tert-butylstyrene and 9-vinylanthracene. In the instance of 9-vinylanthracene, the rearrangement product is tribenzo–pentaphene, which is formed in 50% of conversions. Full article

The complexation of nabumetone (NAB) and naproxen (NAP) with cucurbit[7]uril (CB7) was investigated in aqueous solution by isothermal titration microcalorimetry, mass spectrometry, NMR spectroscopy, and computation methods. High-resolution mass spectrometry was used for the determination of the binding stoichiometry and the gas-phase stability of the drug–CB7 complex. The doubly charged NH₄⁺ or Na⁺ adducts of the 1:1 complex were observed in the mass spectra. The dissociation of complexes was monitored at different collision energies, (1–16) eV, leading to the neutral loss of NH₃ and the drug, with charge retention observed on CB7. By performing ITC experiments, all the thermodynamic parameters were determined for the NAB-CB7 complex in water at 25 °C. The corresponding values amounted to the following: logK = 4.66 ± 0.01; Δ_rG° = −26.7 ± 0.1 kJ/mol; Δ_rH° = −20.2 ± 0.7 kJ/mol; TΔ_rS° = 6.4 ± 0.8 kJ/mol, i.e., the formation of the inclusion complex is enthalpy driven and has a favorable entropy. The inclusion phenomena were further confirmed by NMR spectroscopy (¹H, ROESY, and DOSY), suggesting the encapsulation of the naphthalene ring of both drugs inside the CB7 cavity. The results of the DFT calculations and the IGMH analysis were in accordance with the experimental ones, suggesting that van der Waals interactions play a major role in drug–CB7 complexation. Full article

Xanthones are a group of polyphenolic compounds widely known to have antitumor, anti-inflammatory, antibacterial, antifungal, antiviral, and antioxidant properties. To fully utilize their therapeutic potential, this study aimed to enhance the solubility of a poorly soluble xanthone by preparing a 1:1 molar ratio of xanthone–urea complex utilizing a cogrinding method via a vibration rod mill. DSC analysis revealed the disappearance of the characteristic endothermic peaks of xanthone (177 °C) and urea (136 °C) in the ground mixture (GM), along with the appearance of a new endothermic peak at 185 °C, indicating potential complexation. Additionally, new peaks were observed in the PXRD patterns of the GM at 9.1°, 12.0°, 14.0°, 18.6°, 19.6°, and 24.6°, suggesting structural changes that were also observed in SEM morphology. FTIR spectroscopy revealed significant shifts in the -NH and C=O peaks of xanthone and urea, as well as the disappearance of a -CN peak. Altered diffusion coefficients for both xanthone and urea were measured using DOSY-NMR, accompanied by notable improvements in solubility and dissolution profiles. The GM exhibited nearly a 2-fold increase in solubility, reaching 88.08 ± 1.25 µg/mL at 24 h and 90.97 ± 0.98 µg/mL at 72 h, alongside a 2-fold and 5-fold increase in dissolution at 0.21 µg/mL and 0.51 µg/mL for the physical mixture (PM) and GM, respectively. Furthermore, an enhanced antioxidant capacity was observed, as demonstrated in the calculated Trolox equivalent (TE) value, which increased from 1.48 ± 1.12 for xanthone alone to 1.65 ± 1.03 in the xanthone–urea complex. These findings confirm the successful complexation of xanthone and urea in a 1:1 molar ratio. Full article

Deep eutectic solvents (DESs) are environmentally friendly solvents formed by combining hydrogen bond donors and acceptors, resulting in a eutectic mixture with a lower melting point than the individual components. While there is extensive research on the electrochemical synthesis of platinum nanoparticles in DESs, to the best of our knowledge, there are no studies on the chemical reactivity of platinum(II) complexes in these systems. This study investigates the simple model reaction between K₂PtCl₄ and ethylenediamine (en), exploring the behaviour in DES environment, to optimize the synthesis of simple cisplatin-like platinum compounds with the potential objective of improving the traditional methods, decreasing the number of steps required for obtaining target compounds and reducing chemical waste. The reactions were performed in two hydrophilic DESs: choline chloride:glycerol 1:2 (glyceline, GL) and choline chloride:ethylene glycol 1:2 (ethaline, EG). The experiments, conducted in a 70% (v/v) DES and 30% 1:1 H₂O/D₂O mixture to allow for direct NMR analysis, revealed that en quickly formed [PtCl₂(en)], which further reacted to produce [Pt(en)₂]Cl₂. Reaction products were characterised by 1D (¹H and ¹⁹⁵Pt{¹H}) and 2D ([¹H,¹³C]-HSQC and [¹H,¹⁵N]-HSQC) NMR experiments. The discolouration of solutions, due to the consumption of K₂PtCl₄, and the precipitation of the purple Magnus salt [Pt(en)₂][PtCl₄] occurred over time. The main observed difference between the two solvent mixtures was the slower reactivity in glyceline, due to the much higher viscosity of the solution. Diffusion-ordered spectroscopy (DOSY) indicated lower water mobility in DES mixtures than pure water, with the reaction products closely associated with DES molecules. Full article

Covalent organic frameworks (COFs) hold promising potential as high-temperature proton conductors due to their highly ordered nanostructures and high specific surface areas. However, due to their limited functional groups and poor membrane-engineering properties, finding practical applications for COF-based proton-conducting materials still remains challenging. Herein, we proposed a universal strategy to fabricate proton-conducting composite membranes by the incorporation of sulfonic acid-bearing COFs and zwitterionic poly(ionic liquid)s (PILs) via in situ polymerization. Zwitterionic PILs with methanesulfonate counter ions can work as the intrinsic proton sources, and the sulfonic acid groups on the COF nanochannels can act as the extrinsic proton suppliers. Benefiting from the spatial nanoconfinement of long-range ordered nanochannels and the enhanced electrostatic interactions with PILs, the COFs with high densities of sulfonic acid groups can endow the as-prepared composite membrane (PIL@TpBD(SO₃H)₂) with a comparable anhydrous proton conductivity of 3.20 × 10⁻³ S cm⁻¹ at 90 °C, which is much higher than that of conventional Nafion (~10⁻⁵ S cm⁻¹ at 90 °C under anhydrous condition). ¹H NMR DOSY spectra reveal that both the diffusion and dissociation of protons can be drastically facilitated upon nanoconfinement, demonstrating the promising efficiency of nanochannels in proton conduction. Moreover, the obtained composite membranes possess outstanding mechanical and thermal stability, which is crucial for their practical application. This study demonstrates proton conduction elevation in nanoconfined PILs and provides a promising insight into the engineering of stable COF-based proton-conducting materials. Full article

Background/Objectives: Doxorubicin (Dox) is an anticancer drug used in the treatment of a wide range of solid tumors; however, Dox causes systemic toxicity and irreversible cardiotoxicity. The design of a new nanosystem that allows for the control of Dox loading and delivery results is a powerful tool to control Dox release only in cancer cells. For this reason, supramolecular self-assembly was performed between a poly(amidoamine) (PAMAM) dendrimer decorated with four β-cyclodextrin (βCD) units (PAMAM-βCD) and an adamantane–hydrazone–doxorubicin (Ad-h-Dox) prodrug. Methods: The formation of inclusion complexes (ICs) between the prodrug and all the βCD cavities present on the surface of the PAMAM-βCD dendrimer was followed by ¹H-NMR titration and corroborated by 2D NOESY experiments. A full characterization of the supramolecular assembly was performed in the solid state by thermal analysis (DSC/TGA) and scanning electron microscopy (SEM) and in solution by the DOSY NMR technique in D₂O. Furthermore, the Dox release profiles from the PAMAM-βCD/Ad-h-Dox assembly at different pH values was studied by comparing the efficiency against a native βCD/Ad-h-Dox IC. Additionally, in vitro cytotoxic activity assays were performed for the nanocarrier alone and the two supramolecular assemblies in different carcinogenic cell lines. Results: The PAMAM-βCD/Ad-h-Dox assembly was adequately characterized, and the cytotoxic activity results demonstrate that the nanocarrier alone and its hydrolysis product are innocuous compared to the PAMAM-βCD/Ad-h-Dox nanocarrier that showed cytotoxicity equivalent to free Dox in the tested cancer cell lines. The in vitro drug release assays for the PAMAM-βCD/Ad-h-Dox system showed an acidic pH-dependent behavior and a prolonged profile of up to more than 72 h. Conclusions: The design of PAMAM-βCD/Ad-h-Dox consists of a new controlled and prolonged Dox release system for potential use in cancer treatment. Full article

The Nd-mediated coordinative chain transfer polymerization (CCTP) of dienes represents one of the state-of-the-art techniques in the current synthetic rubber field. Besides having well-controlled polymerization behaviors as well as high atom economies, it also allows for the generation of highly reactive Al-capped polydienyl chain-ends, which hold great potential, yet much less explored up to date, in achieving end functionalization to mimic the structure of natural rubber. In this study, we demonstrate an efficient in situ method to realize end-functionalizing polyisoprene by introducing epoxide compounds into a CCTP system. The end functionalization efficiency was 92.7%, and the obtained polymers were systematically characterized by ¹H NMR, ¹H,¹H-COSY NMR, DOSY NMR, and MALDI TOF. NMR studies revealed that a maximum of two EO units were introduced to the chain ends, and based on density functional theory (DFT) studies, an energy barrier of 33.3 kcal/mol was required to be overcome to open the ring of the EO monomer. Increasing the ratio of [Ip]/[Nd] resulted in gradually increased viscosities for the reaction medium and therefore gave rise to an end functionalization efficiency that decreased from 92.7% to 74.2%. The end hydroxyl group can also be readily converted to other functionalities, as confirmed by NMR spectroscopy. Full article

The amount of free ions, ion pairs, and higher aggregate of the possible species present in a solution during the gold(I)-catalyzed alkoxylation of unsaturated hydrocarbon, i.e., ISIP (inner sphere ion pair) [(NHC)AuX] and OSIP (outer sphere ion pairs) [(NHC)Au(TME)X] [NHC 1,3-bis(2,6-di-isopropylphenyl)-imidazol-2-ylidene; TME = tetramethylethylene (2,3-bis methyl-butene); X⁻ = Cl⁻, BF₄⁻, OTf⁻; and OTs⁻ BArF₄⁻ (ArF = 3,5-(CF₃)₂C₆H₃)], has been determined. The ¹H and ¹⁹F DOSY NMR measurements conducted in catalytic conditions indicate that the dissociation degree (α) of the equilibrium ion pair/free ions {[(NHC)Au(TME)X] [(NHC)Au(TME)]⁺ + X⁻} depends on the nature of the counterion (X⁻) when chloroform is the catalytic solvent: while the compounds containing OTs⁻ and OTf⁻ as the counterion gave a low α (which means a high number of ion pairs) of 0.13 and 0.24, respectively, the compounds containing BF₄⁻ and BArF₄⁻ showed higher α values of 0.36 and 0.32, respectively. These results experimentally confirm previous deductions based on catalytic and theoretical data: the lower the α value, the greater the catalytic activity because the anion that can activate methanol during a nucleophilic attack, although the lower propensity to activate methanol of BF₄⁻ and BArF₄⁻, as suggested by the DFT calculations, cannot be completely overlooked. As for the effect of the solvent, α increases as the dielectric constant increases, as expected, and in particular, green solvents with high dielectric constants show a very high α (0.90, 0.84, 0.80, and 0.70 for propylene carbonate, γ-valerolactone, acetone, and methanol, respectively), thus confirming that the moderately high activity of NHC-Au-OTf in these solvents is due to the specific effect of polar functionalities (O-H, C=O, O-R) in activating methanol. Finally, the DOSY measurements conducted in p-Cymene show the formation of quadrupole species: under these conditions, the anion can better exercise its ‘template’ and ‘activating’ roles, giving the highest TOF. Full article

With direct application to current and future consumer healthcare products, this research sheds light on the importance of packaging and its potential effects on both Active Pharmaceutical Ingredient (API) delivery and stability. Industrially sourced, proprietary experimental formulations (PEFs), specifically oral cleansers, based on salicylic acid and hydrogen peroxide, discolored over time at different rates, depending on packaging type used. This discoloration stemmed from an interplay of two factors, involving both spontaneous formulation degradation and the interaction of both degradants and salicylic acid with the internal surface of the packaging. This manuscript reports on the investigation to uncover the origins of discoloration. To investigate this real-world, industrial pipeline problem, we exploited the high dimensionality and simple sample preparation uniquely afforded by NMR. Using a combination of 1D/2D NMR and diffusion-ordered NMR spectroscopy (DOSY) to leverage molecular mass estimations from, we not only quickly confirmed the identities of these degradants, but also assessed their formation as a function of temperature and pH, providing insight into the mechanisms underlying their formation. We were able to identify catechol as the main source of discoloration over a period of several weeks, being formed at the ppm level. Furthermore, we evaluated the formulation–container interaction, employing NMR, ICP-MS, and ATR-IR. Despite this comprehensive analysis, the root causes of discoloration could only tentatively be assigned to a surface Ti complex of salicylic acid and other hydroxy carboxylic acids. Through the understanding of formulation degradation pathways, we were able to support further toxicology assessment, vital to both consumer safety and the manufacturer. This work underscores the invaluable role of NMR in the analysis of intricate proprietary mixtures with a consumer-centric purpose. Our findings demonstrate that conventional analytical techniques falter in the face of such complexity, requiring extensive preparation and pre-analytical processing, highlighting the novelty and crucial relevance of NMR research to manufacturers and consumers. Such an analysis is of value in the pursuit of materials within the consumer-healthcare space, which meet the requirements for successful recycling or re-use. Full article

Abiraterone acetate (AbirAc) is the most used steroidal therapeutic agent for treatment of prostate cancer. The mainly hydrophobic molecular surface of AbirAc results in its poor solubility and plays an important role for retention of abiraterone in the cavity of the receptor formed by peptide chains and heme fragments. In order to evaluate the hydrolytic stability of AbirAc, to modify its solubility by formation of new solid forms and to model bonding of this medication with the heme, a series of d-metal complexes with AbirAc was obtained. AbirAc remains stable in water, acetonitrile, tetrahydrofuran, and ethanol, and readily interacts with dications as a terminal ligand to create discrete complexes, including [FePC(AbirAc)₂] and [ZnTPP(AbirAc)] (H₂PC = phthalocyanine and H₂TPP = 5,10,15,20-tetraphenylporphyrine) models for ligand–receptor bonding. In reactions with silver(I) nitrate, AbirAc acts as a bridge ligand. Energies of chemical bonding between AbirAc and these cations vary from 97 to 235 kJ mol⁻¹ and exceed those between metal atoms and water molecules. This can be indicative of the ability of abiraterone to replace solvent molecules in the coordination sphere of biometals in living cells, although the model [ZnTPP] complex remains stable in CDCl₃, CD₂Cl₂, and 1,1,2,2-tetrachloroethane-d₂ solvents and decomposes in polar dimethylsulfoxide-d₆ and methanol-d₄ solvents, as follows from the ¹H DOSY spectra. Dynamics of its behavior in 1,1,2,2-tetrachloroethane-d₂ were studied by ROESY and NMR spectra. Full article

Malaria is one of the major life-threatening health problems worldwide. Artesunate is the most potent antimalarial drug to combat severe malaria. However, development of drug resistance, short plasma half-life, and poor bioavailability limit the efficacy of this drug. Here, we applied the dimerization concept to synthesize dimeric artesunate glycerol monocaprylate conjugate (D-AS-GC) by conjugating artesunate (AS) with glycerol monocaprylate (GC) via esterification reaction. D-AS-GC conjugate, AS, and GC were well characterized by ¹H NMR, attached proton test (APT) ¹³C NMR and 2D NMR spectroscopy. D-AS-GC conjugate was further analyzed by ESI-TOF MS. Finally, a series of nanoemulsion preconcentrate (F1–F6) of D-AS-GC was prepared by mixing different ratios of oil and surfactant/cosurfactant and evaluated after dilution with an aqueous phase. The optimized formulation (F6) exhibits a clear nanoemulsion and the hydrodynamic diameter of the dispersed phase was determined by DLS and DOSY NMR spectroscopy. The morphology of the nanoemulsion droplets of F6 was investigated by AFM, which revealed the formation of tiny nanoemulsion droplets on a hydrophilic mica substrate. Moreover, using a less polar silicon wafer led to the formation of larger droplets with a spherical core shell-like structure. Overall, the rational design of the dimeric artesunate-based nanoemulsion preconcentrate could potentially be used in more efficient drug delivery systems. Full article

The copolymerization of carbon dioxide (CO₂) with epoxides demonstrates promise as a new synthetic method for low-carbon polymer materials, such as aliphatic polycarbonate materials. In this study, a binary Schiff base cobalt system was successfully used to catalyze the copolymerization of 1,2-butylene oxide (BO) and CO₂ and its terpolymerization with other epoxides such as propylene oxide (PO) and cyclohexene oxide (CHO). ¹H nuclear magnetic resonance (¹H NMR), diffusion-ordered spectroscopy (DOSY), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC) confirmed the successful synthesis of the alternating terpolymer. In addition, the effects of the polymerization reaction conditions and copolymerization monomer composition on the polymer structure and properties were examined systematically. By regulating the epoxide feed ratio, polycarbonates with an adjustable glass transition temperature (T_g) (11.2–67.8 °C) and hydrophilicity (water contact angle: 85.2–95.2°) were prepared. Thus, this ternary polymerization method provides an effective method of modulating the surface hydrophobicity of CO₂-based polymers and their biodegradation properties. Full article

To date, nickel(II) complexes have not been practically investigated as catalysts in ring-opening polymerization (ROP) of lactide to produce biodegradable poly(lactic acid), which is in demand in biomedicine and industry. In this study, carboxylate complexes of nickel(II) containing various N-donor ligands with different nuclearity, metal core rigidity and nature of carboxylate ligands were synthesized and studied by infrared spectroscopy, X-ray diffraction, elemental and thermogravimetric analyses. The obtained complexes were examined in the ROP of the rac-lactide in bulk and in toluene solution with and without the addition of a benzyl alcohol initiator. In the series of complexes studied, the complex [Ni(DBED)₂(O₂CC(CH₃)₃)₂]·(CH₃)₃CCO₂H (DBED is N,N′-dibenzylethylenediamine) was a syndioselective catalyst and showed the highest catalytic ability in the polymerization without the addition of benzyl alcohol. For this complex, according to 1D DOSY ¹H NMR spectroscopy and mass spectrometry with electrospray ionization, polymerization is initiated by a free secondary amine, DBED, leaving the metal’s inner coordination sphere. Based on the experimental data obtained, a comprehensive density functional theory (DFT) study of the ROP pathways including the initiation and first chain growth cycle steps with a detailed description of the intermediates and evaluation of the energy barriers of the steps was carried out. It was shown that one of the key roles in the reaction process is played by carboxylate ligands, which act as proton carriers from the initiator molecule and have a significant influence on the reactivity of the catalytic metal complexes. Full article