RESUMO

One of the most recent focuses in supramolecular chemistry is developing molecules designed to exhibit programmable properties at the molecular level. Rotaxanes, which function as molecular machines with movements controlled by external stimuli, are prime candidates for this purpose. However, the controlled synthesis of rotaxanes, especially amide-benzylic rotaxanes with more than two components, remains an area ripe for exploration. In this study, we aim to elucidate the formation of amide-benzylic [3]rotaxanes using a thread that includes a conventional succinamide station and an innovative triazole-carbonyl station. Including the triazole-carbonyl station introduces new perspectives into the chemistry of rotaxanes, influencing their conformation and dynamics. The synthesis of two-station rotaxanes with varying stoppers demonstrated that the macrocycle consistently occupies the succinamide station, providing greater stability as evidenced by NMR and SC-XRD analyses. The presence of a triazole-carbonyl station facilitated the formation of a second macrocycle exclusively when a secondary amide was employed as the stopper group, presumably due to decreased steric hindrance. Moreover, the second macrocycle directly forms at the triazole-carbonyl station. This investigation reveals that slight modifications in the thread structure can dramatically impact the formation, stability, and interactions between components of rotaxanes.

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The 1-acyl thiourea family [R1C(O)NHC(S)NR2R3] exhibits the flexibility to incorporate a wide variety of substituents into their structure. The structural attributes of these compounds are intricately tied to the type and extent of substitution. In the case of 3-mono-substituted thioureas (R2=H), the conformational behavior is predominantly shaped by the presence of an intramolecular N-H ⋅ ⋅ ⋅ O=C hydrogen bond. This study delves into the structural consequences stemming from the inclusion of substituents possessing hydrogen-donor capabilities within four novel 1-acyl-3-mono-substituted thiourea derivatives. A comprehensive suite of analytical techniques, encompassing FTIR, Raman spectroscopy, multinuclear (1H and 13C) NMR spectroscopy, single-crystal X-ray diffraction, and supported by computational methods, notably NBO (Natural Bond Orbital) population analysis, Hirshfeld analysis, and QTAIM (Quantum Theory of Atoms in Molecules), was harnessed to scrutinize and characterize these compounds. In the crystalline state, these compounds exhibit an intricate interplay of intermolecular interactions, prominently featuring an expansive network of hydrogen bonds between the hydroxy (-OH) groups and the carbonyl and thiocarbonyl bonds within the 1-acyl thiourea fragment. Notably, the topological analysis underscores significant distinctions in the properties of the acyl thiourea fragment and the intramolecular >C=O ⋅ ⋅ ⋅ H-N bond when transitioning from the isolated molecule to the crystalline environment.

RESUMO

Ammeline (AM) is a molecule with a very low reputation in the field of supramolecular community, but with a recently proven potential both experimentally and theoretically. In this work, dispersion-corrected density functional theory (DFT-D) computations and molecular dynamics (MD) simulations were employed to understand the aggregation mechanism of AM in chloroform and water media. Our DFT-D and MD analyzes show that the most important interactions are those formed by the amine groups (-NH2) with both the pyridine-type nitrogen atoms and the carbonyl groups (C=O). In the more polar solvent, the interactions between water molecules and the C=O group prevent the AM from forming more interactions with itself. Nevertheless, four types of dimers involving N-H∙∙∙O interactions were found to exist in water solutions. The overlooked tetrel bond between endocyclic N and C atoms can also stabilize dimers in solution. Moreover, while most AM dimers are enthalpy-driven, our results indicate that the unique DD-AA dimer (D=donor, A=acceptor) that originates cyclic rosettes is entropy-driven.

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Aim: To develop nanoemulsions (NEs) loading amphotericin B (AmB) and to evaluate the influence of different excipients on the stability and the supramolecular organization, retention and toxicity of AmB. Materials & methods: The NEs were developed from different oils, surfactants, external media and anionic lipids (disteaoryl phosphatidylglycerol [DSPG] and dioleoyl phosphatidylglycerol [DOPG]). Their impact on the size, pH, zeta potential, AmB encapsulation efficiency, AmB retention and hemolytic potential of the NEs was evaluated. Results & conclusion: The use of soybean oil (lipid matrix), Span 80 (surfactant), phosphate buffer (external phase) and DSPG or DOPG (hydrophobic ion pair) provided better NE stability, higher AmB retention within the NEs and a safer formulation profile in hemolysis tests.

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The synthesis of a new family of ethylenediaminetetraacetic acid (EDTA) core dimers and G0 dendrimers end-capped with two and four ß-cyclodextrin (ßCD) moieties was performed by click-chemistry conjugation, varying the spacers attached to the core. The structure analyses were achieved in DMSO-d6 and the self-inclusion process was studied in D2O by 1H-NMR spectroscopy for all platforms. It was demonstrated that the interaction with adamantane carboxylic acid (AdCOOH) results in a guest-induced shift of the self-inclusion effect, demonstrating the full host ability of the ßCD units in these new platforms without any influence of the spacer. The results of the quantitative size and water solubility measurements demonstrated the equivalence between the novel EDTA-ßCD platforms and the classical PAMAM-ßCD dendrimer. Finally, we determined the toxicity for all EDTA-ßCD platforms in four different cell lines: two human breast cancer cells (MCF-7 and MDA-MB-231), human cervical adenocarcinoma cancer cells (HeLa), and human lung adenocarcinoma cells (SK-LU-1). The new EDTA-ßCD carriers did not present any cytotoxicity in the tested cell lines, which showed that these new classes of platforms are promising candidates for drug delivery.

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Herein, we describe the synthesis, crystal structure, and electronic properties of {[K2(dmso)(H2O)5][Ni2(H2mpba)3]·dmso·2H2O}n (1) and [Ni(H2O)6][Ni2(H2mpba)3]·3CH3OH·4H2O (2) [dmso = dimethyl sulfoxide; CH3OH = methanol; and H4mpba = 1,3-phenylenebis(oxamic acid)] bearing the [Ni2(H2mpba)3]2- helicate, hereafter referred to as {NiII2}. SHAPE software calculations indicate that the coordination geometry of all the NiII atoms in 1 and 2 is a distorted octahedron (Oh) whereas the coordination environments for K1 and K2 atoms in 1 are Snub disphenoid J84 (D2d) and distorted octahedron (Oh), respectively. The {NiII2} helicate in 1 is connected by K+ counter cations yielding a 2D coordination network with sql topology. In contrast to 1, the electroneutrality of the triple-stranded [Ni2(H2mpba)3] 2- dinuclear motif in 2 is achieved by a [Ni(H2O)6]2+ complex cation, where the three neighboring {NiII2} units interact in a supramolecular fashion through four R22(10) homosynthons yielding a 2D array. Voltammetric measurements reveal that both compounds are redox active (with the NiII/NiI pair being mediated by OH- ions) but with differences in formal potentials that reflect changes in the energy levels of molecular orbitals. The NiII ions from the helicate and the counter-ion (complex cation) in 2 can be reversibly reduced, resulting in the highest faradaic current intensities. The redox reactions in 1 also occur in an alkaline medium but at higher formal potentials. The connection of the helicate with the K+ counter cation has an impact on the energy levels of the molecular orbitals; this experimental behavior was further supported by X-ray absorption near-edge spectroscopy (XANES) experiments and computational calculations.

RESUMO

We describe the synthesis, crystallographic characterization of a new Cu-Salphen compound and its use as a host Lewis-acid against guest anions in two versions: a) free molecule, b) copolymerized with methyl methacrylate:n-butyl acrylate (1 : 4-wt.) as protective co-monomers. Higher contents in Cu-Salphen yielded larger and more homogeneous polymer sizes. Polymer size together with glass transitions, heat capacity, thermal degradation, guest-saturation degrees and host-guest species distribution profiles from spectrophotometric titrations explained growths of up to 630-fold in K11 and 180000-fold in K12 for the host's binding site attributable to a solvophobic protection from the macromolecular structure. Spectrofluorimetry revealed blue-shifted×13-16 larger luminescence for Cu-Salphen in the polymers (λem =488-498 nm) than that of the non-polymerized counterpart (λem =510-543 nm) and "turn-on" blue-shifted enhanced fluorescence upon guest association. We propose a cooperative incorporation of the guests occurring from the outer medium toward internally protected binding site pockets in the random coil polymer conformations.

RESUMO

A pseudo-rotaxane is a host-guest complex composed of a linear molecule encircled by a macrocyclic ring. These complexes can be assembled by sliding the host over the guest terminal groups. If there is a close match between the molecular volume of the flanking groups on the guest and the cavity size of the macrocycle, the slipping might occur slowly or even become completely hindered. We have previously shown that it is possible to overcome the restraints imposed by steric effects on the sliding process by integrating electrostatic attractive interactions during the slipping step. In this work, we extend our electrostatically assisted slipping approach (EASA) to a new host-guest system featuring a flexible macrocyclic ring and a series of asymmetric guests containing a cyclic tertiary ammonium group. Compelling evidence for pseudo-rotaxane formation is presented, along with thermodynamic and kinetic data. Experimental results suggests that the higher conformational flexibility of 24-crown-8 significantly increases the sliding rate, compared with the more rigid dibenzo-24-crown-8, without affecting complex stability. Furthermore, by combining the EASA and macrocycle flexibility, we were capable to slip a large eight-membered cyclic group across the 24-crown-8 annulus, setting a new limit on the ring molecular size that can pass through a 24-membered crown ether.

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The synthesis, crystal structure and spectroscopic and electronic properties of N-(2-methyl-5-nitrophenyl)-4-(pyridin-2-yl)pyrimidin-2-amine (NPPA), C16H13N5O2, a potential template for drug design against chronic myelogenous leukemia (CML), is reported. The design and construction of the target molecule were carried out starting from the guanidinium nitrate salt (previously synthesized) and the corresponding enaminone. X-ray diffraction analysis and a study of the Hirshfeld surfaces revealed important interactions between the nitro-group O atoms and the H atoms of the pyridine and pyrimidine rings. A crystalline ordering in layers, by the stacking of rings through interactions of the π-π type, was observed and confirmed by a study of the shape-index surfaces and dispersion energy calculations. Quantitative electrostatic potential studies revealed the most positive value of the molecule on regions close to the N-H groups (34.8 kcal mol-1); nevertheless, steric impediments and the planarity of the molecule do not allow the formation of hydrogen bonds from this group. This interaction is however activated when the molecule takes on a new extended conformation in the active pocket of the enzyme kinase (PDB ID 2hyy), interacting with protein residues that are fundamental in the inhibition process of CML. The most negative values of the molecule are seen in regions close to the nitro group (-35.4 and -34.0 kcal mol-1). A molecular docking study revealed an energy affinity of ΔG = -10.3 kcal mol-1 for NPPA which, despite not having a more negative value than the control molecule (Imatinib; ΔG = -12.8 kcal mol-1), shows great potential to be used as a template for new drugs against CML.

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The synthesis, characterization and crystallographic analysis is reported of a new Nickel Salphen complex and its radical copolymerization with n-butyl acrylate and methyl methacrylate to produce novel host macromolecules with tunable association against guest anions. Spectrophotometric titrations of the complex and of the polymers revealed that a supramolecular regulation of guest-binding accessibility was enabled by the number of Ni-Salphen units per chain. The latter content in turn, determined the chain size and molecular weight uniformity upon polymerization, and likely increased the strength in interchain/intrachain non-covalent interactions over the nickel center and the acrylic domains. The study also showed that incorporation of the monomer into the acrylic polymer backbone opened the possibility for the nickel binding site to gain access to host:guest stoichiometric discrimination, switching from 1 : 1 (major) and 1 : 2 (minor) both coexisting for the host when in the free form, to mostly 1 : 2 when in the polymerized version.

RESUMO

Nowadays, the use of sulfur-based ligands to modify gold-based materials has become a common trend. Here, we present a theoretical exploration of the modulation of the chalcogenides-gold interaction strength, using sulfur, selenium, and tellurium as anchor atoms. To characterize the chalcogenide-gold interaction, we designed a nanocluster of 42 gold atoms (Au42) to model a gold surface (111) and a series of 60 functionalized phenyl-chalcogenolate ligands to determine the ability of electron-donor and -withdrawing groups to modulate the interaction. The analysis of the interaction was performed by using energy decomposition analysis (EDA), non-covalent interactions index (NCI), and natural population analysis (NPA) to describe the charge transfer processes and to determine data correlation analyses. The results revealed that the magnitudes of the interaction energies increase following the order S < Se < Te, where this interaction strength can be augmented by electron-donor groups, under the donor-acceptor character the chalcogen-gold interaction. We also found that the functionalization in meta position leads to better control of the interaction strength than the ortho substitution due to the steric and inductive effects involved when functionalized in this position.

RESUMO

The thermodynamic stability of 1 : 1 and 2 : 1 boron-nitrogen (B←N) adducts formed between aromatic boronic esters with mono- and diamines was studied in solution by NMR and UV-vis spectroscopy with association energies (ΔG°) ranging from -11 to -28 kJ mol-1 . The effect of different substituents in the boronic ester, the nature of the diamine linker, and the effect of the solvent was explored. Stable 2 : 1 B←N adducts with diamines such as 1,3-diaminopropane were produced in solutions of hydrogen-bonding acceptor solvents (acetonitrile and ethyl acetate), which can be isolated in the solid state as crystalline solvates, whereas the use of noncoordinating solvents such as 1,2-dichloroethane afforded mainly 1 : 1 B←N adducts. In suitable combinations, aromatic bis-pyridyl diamines produced stable 2 : 1 B←N adducts that were isolated either as solvent-free solids, solvates, or cocrystals. In these crystalline forms, double-tweezer hosts were observed with an exceptional syn/anti conformational guest-adaptability driven by simultaneous donor-acceptor and C-H⋅⋅⋅π interactions in the tweezer cavities, resembling preorganized covalent tweezer hosts. Interestingly, cocrystals with electron-rich guests such as tetrathiafulvalene and pyrene showed non-centrosymmetric crystal lattices with infinite π-stacked donor-acceptor columns.

RESUMO

4,5-Bis(phtalimidomethyl)acridine (L) was studied as a chemosensor for metal ions in alcoholic matrices and showed to be selective for Al3+, through a linear fluorescence enhancement of 230% in the concentration range of 10-70 µmol L-1. Benesi-Hildebrand and Job's formalisms indicated the formation of a 1:1 (Al3+:L) complex with a binding constant of 6.30 × 103 L mol-1. DFT/TDDFT calculations allowed access to the energies of frontier orbitals and could explain the fluorescence augmentation upon complex formation, due to the restraining of PET process. Limit of detection and limit of quantification (R2 = 0.998, least squares method) are 1.130 and 3.768 µmol L-1, respectively, and validation was verified based on the variation of several analytical conditions. Practical application in spiked Brazilian sugarcane spirit showed recovery of (84 ± 0.42)% with no effect of interfering ions.

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Polyamine-salt aggregates (PSA) are biomimetic soft materials that have attracted great attention due to their straightforward fabrication methods, high drug-loading efficiencies, and attractive properties for pH-triggered release. Herein, a simple and fast multicomponent self-assembly process was used to construct cross-linked poly(allylamine hydrochloride)/phosphate PSAs (hydrodynamic diameter of 360 nm) containing glucose oxidase enzyme, as a glucose-responsive element, and human recombinant insulin, as a therapeutic agent for the treatment of diabetes mellitus (GI-PSA). The addition of increasing glucose concentrations promotes the release of insulin due to the disassembly of the GI-PSAs triggered by the catalytic in situ formation of gluconic acid. Under normoglycemia, the GI-PSA integrity remained intact for at least 24 h, whereas hyperglycemic conditions resulted in 100 % cargo release after 4 h of glucose addition. This entirely supramolecular strategy presents great potential for the construction of smart glucose-responsive delivery nanocarriers.

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A new acridine-based chemosensor was prepared, characterized and investigated for quantitative detection of Hg2+ ions in aqueous solutions. DFT and TD-DFT calculations showed that formation of a coordination bond between Hg2+ and the thiolate-sensor accounts for the fluorescence quenching, forming [HgLSCl2]2- as the most stable species. Limit of detection and limit of quantification were as low as 4.40 and 14.7 µmol L-1, respectively (R2 = 0.9892, least squares method), and a linear concentration range of 14.7-100 µmol L-1. Benesi-Hildebrand and Job formalisms are in accordance with the formation of a stable complex with a 1:1 (metal ion/sensor) ratio, and a determined binding constant of 5.14 × 103 L mol-1. Robustness was verified based on the variation of several analytical conditions. In addition, the method presented maximum relative standard deviation of 4.6%, and recovery results was (90.3 ± 4,6)% from distilled water, with no effect of interfering ions. Analytical figures of merit showed that the sensor can be an attractive low cost alternative for detection of Hg2+.

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RESUMO

The use of the electrostatic stoppers concept in the field of mechanically interlocked molecules is reported; these stoppers are chemically sensitive end groups on a linear guest molecule that allows for the conversion of a pseudo-rotaxane species into a rotaxane complex by a change in the medium acidity. The chemical stimulus causes the appearance of negative charges on both ends of the linear component, passing from cationic to anionic, and causing a significant ring-to-axle electrostatic repulsion. This phenomenon has two different and simultaneous effects: 1) destabilizes the complex as a consequence of confining an anionic ring into an anionic axle, and 2) increases the dissociation energy barrier, thus impeding ring extrusion. This newly formed metastable rotaxane species is resistant to solvent and temperature effects and performs as a two-state degenerated molecular shuttle in solution.

RESUMO

Ionically crosslinked poly(allylamine)/phosphate (PAH/Pi) colloids consist of self-assembled nanostructures stabilized by supramolecular interactions. Under physiological conditions, these interactions should be present at high ionic strength and only in a narrow pH window to be effective as drug delivery agents. In this work we study the effect of the pH and ionic strength in the chemical behaviour of inorganic phosphate (Pi), poly(allylamine hydrochloride) (PAH) and their mixture in aqueous solution (PAH-Pi). By combination of experimental measurements and a theoretical model, we demonstrate that the driving force that leads to the formation of colloids is the electrostatic pairing between the positively charged amino groups in PAH and negatively charged HPO42- ions. Increasing the ionic strength of the system by addition of KCl weakens the PAH-Pi interactions and narrows the pH stability window from 4 to 1.8 pH units. In addition, a fully reversible system was obtained in which the colloids assemble and disassemble by changing the pH between 6.8 and 7.1 at high ionic strength, making them suitable for use as pH-responsive nanocarriers.

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Abstract The synthesis of new grid-type complexes of Co2+ and Fe2+ based on a highly soluble double hydrazone framework is reported. The data obtained from 1H NMR, FT-IR, and elemental analysis indicate that the complexes adopted a grid-like structure. Electronic properties of the metallogrids were analyzed by UV-Vis spectroscopy in chloroform, methanol, and dichloromethane. Additionally, cyclic voltammetry and square wave voltammetry were carried out in N,N-dimethylformamide (DMF). These compounds exhibited two oxidation processes corresponding to the organic ligand and several reductions events, comprising the ligand and metal centers. Furthermore, the interplay between the metal nature and the ligand framework was also studied in detail. These results represent an advancement in the chemistry of metallogrids not only because of the few reports concerning to the electrochemical properties found in the literature, but also for the design of novel hydrazone ligands of high solubility and easy preparation.

Resumen Se reporta la síntesis de nuevos complejos metálicos de Co2+ y Fe2+ tipo rejilla que contienen como ligando orgánico una doble hidrazona altamente soluble en solventes orgánicos. Los datos obtenidos de resonancia magnética nuclear (RMN 1H), espectroscopía infrarroja con transformada de Fourier (FT-IR) y análisis elemental indican que los complejos adoptaron una estructura de tipo rejilla. Las propiedades electrónicas de las metalo-rejillas fueron analizadas a través de espectroscopía UV-Vis en cloroformo, metanol y diclorometano. Adicionalmente, se realizaron medidas de voltamperometría cíclica y voltametría de onda cuadrada en DMF. Los complejos exhibieron dos procesos de oxidación atribuidos al ligando orgánico y a varios eventos reductivos que comprometían al ligando y a los centros metálicos, por tanto, la interacción entre la naturaleza del ion metálico y la estructura del ligando fue analizada en detalle. Estos resultados representan un avance en la química de metalo-rejillas no solo por los escasos reportes de propiedades electroquímicas encontrados en la literatura, sino también por el diseño de nuevos ligandos hidrazónicos de alta solubilidad y fácil preparación.

Resumo Neste trabalho relata-se a síntese de novos complexos de Co2+ e Fe2+ tipo grelha baseados na estrutura de uma hidrazona dupla altamente solúvel em solventes orgânicos. Os dados obtidos de ressonância magnética nuclear (1H RMN), espectroscopia de infravermelho com transformada de Fourier (FT-IR), e análise elementar indicam que os complexos adotaram a estrutura tipo grelha. As propriedades eletrônicas das grelhas metálicas foram analisadas por espectroscopia UV-Vis em clorofórmio, metanol e diclorometano. Adicionalmente, foram realizadas medidas de voltametria cíclica e voltametria de onda quadrada em DMF. Os compostos estudados exibiram dois processos de oxidação correspondentes ao ligando orgânico, e a vários eventos redutivos que envolvem o ligando orgânico e os centros metálicos. Além disso, a interação entre a natureza do metal e a estrutura do ligando foi estudada em detalhe. Estes resultados representam um avanço na química de metalo-grelhas não somente pelos escassos relatos de propriedades eletroquímicas encontrados na literatura, mas também pelo design de novos ligandos hidrazônicos de alta solubilidade e fácil preparação.

RESUMO

A family of six homoleptic [CuI (Ln )]2 (ClO4 )2 and six heteroleptic [CuI (Ln )(PPh3 )2 ]2 (ClO4 )2 bimetallic complexes, in which Ln are bis-Schiff base ligands with alkyl spacers of variable length (n=2-7 -CH2 -), were prepared to evaluate the role of the spacer on the formation of helicates or mesocates. In the homoleptic series, spectroscopic and theoretical studies indicate that preferences for a conformation are based on energetic parameters, mainly, the establishment of noncovalent interactions. The odd-even nature of the spacers preconditions the superposition of the aromatic rings to allow the juxtaposition necessary for noncovalent interactions, whereas the increase of the length reduces the strength of such interactions. Consequently, complexes with even-spacers of short length were identified as helicates in solution, [CuI (Ln )]22+ (n=2, 4). Complexes [CuI (Ln )]22+ (n=3-7) dissociate in solution to produce the monometallic complexes in equilibrium, [CuI (Ln )]+ . The stability of the bimetallic species is discussed in terms of their conformations. The set of heteroleptic complexes was prepared to evaluate the reach of the "odd-even rule" in the solid, which is based on the "zig-zag" arrangements of the spacers. Based on crystallographic information, "S-" and "C"-type conformations of Ln are related to even and odd spacers, respectively. This trend is considered in addition to other factors to explain preferences for either a mesocate or helicate conformation in the homoleptic series.

RESUMO

A CoII /porphyrinate-based macrocycle in the presence of a 3,5-diphenylpyridine axial ligand functions as an endotopic ligand to direct the assembly of [2]rotaxanes from diazo and styrene half-threads, by radical-carbene-transfer reactions, in excellent 95 % yield. The method reported herein applies the active-metal-template strategy to include radical-type activation of ligands by the metal-template ion during the organometallic process which ultimately yields the mechanical bond. A careful quantitative analysis of the product distribution afforded from the rotaxane self-assembly reaction shows that the CoII /porphyrinate subunit is still active after formation of the mechanical bond and, upon coordination of an additional diazo half-thread derivative, promotes a novel intercomponent C-H insertion reaction to yield a new rotaxane-like species. This unexpected intercomponent C-H insertion illustrates the distinct reactivity brought to the CoII /porphyrinate catalyst by the mechanical bond.