The rational design and selective self-assembly of flexible and unsymmetric ligands into large coordination complexes is an eminent challenge in supramolecular coordination chemistry. Here, we present the coordination-driven self-assembly of natural ursodeoxycholic-bile-acid-derived unsymmetric tris-pyridyl ligand (L) resulting in the selective and switchable formation of chiral stellated Pd6L8 and Pd12L16 cages. The selectivity of the cage originates in the adaptivity and flexibility of the arms of the ligand bearing pyridyl moieties. The interspecific transformations can be controlled by changes in the reaction conditions. The orientational self-sorting of L into a single constitutional isomer of each cage, i.e., homochiral quadruple and octuple right-handed helical species, was confirmed by a combination of molecular modelling and circular dichroism. The cages, derived from natural amphiphilic transport molecules, mediate the higher cellular uptake and increase the anticancer activity of bioactive palladium cations as determined in studies using in vitro 3D spheroids of the human hepatic cells HepG2.

Ruthenium(III) complexes are promising anticancer metallodrugs because of their antimetastatic (migrastatic) potential and significantly lower host toxicity than generally used platinum metallodrugs. On the other hand, the ruthenium(III) complexes generally show low solubility and stability in an aqueous environment but exhibit some toxicity associated with unspecific delivery. For these reasons, numerous ongoing studies deal with their encapsulation into various delivery systems to maximize their therapeutic efficacy. One of these systems can also be crystals of nontoxic metal-organic frameworks (MOFs). In this work, we studied incorporation of a bioactive ruthenium(III) complex (RuC) inside MOFs derived from γ-cyclodextrin (γ-CD) and biocompatible potassium ions, forming CD-MOF-1. Viability studies in vitro were carried out using spheroids of human hepatoblastoma cell line HepG2. These studies revealed that the RuC-CD-MOF-1 system provides effective cancer cell suppression through slow gradual release over a longer period (>10 days) while reducing acute cytotoxic effects associated with naked RuC. This combination was defined for further development and optimization as a drug-delivery platform for metallodrugs.

The majority of known metallosupramolecular gels are based on carefully designed ligands using extensive chemical synthesis. Their gelation is often limited to a certain specific metal salt. We demonstrate that in the presence of a wide group of metal salts natural and readily available folic acid (FA) can act as a supergelator. We report a systematic investigation of 17 mechanically robust FA-based metallogels at extremely low concentrations (<0.2 wt%). Using oscillatory rheological measurements, we further show that these metallogels undergo rapid recovery and self-healing, recovering up to 95% of their original stiffness within 1 min. Among the metallogels studied, FA-chromium(III) acetate gel (0.4 wt%) displayed the highest stiffness with a storage modulus of 4 kPa. More importantly, the stiffness, recovery, and sol ↔ gel transitions can be readily tuned by changing either the metal salt or the concentration. Using a combination of various analytical methods, we also suggest a structure of self-assembly in the metallogel network. This study defines non-toxic FA as a robust and sustainable building block for metallogels-mechanically tunable, multi-responsive soft materials. Finally, as a proof-of-concept experiment, we demonstrate that the FA-chromium(III) acetate gel can be considered as a potent sustainable gellator for enhanced oil recovery applications.

The controlled mass transfer across compartmentalised environments in synthetic nanoreactors is essential for enhancing precise spatiotemporal manipulation of chemical transformations within confined spaces. In this study, we present a strategy that integrates a synthetic anion transporter in liposome-based nanoreactors, allowing for spatiotemporal control over the formation of metal-organic complexes in liposomes. This approach enables us to effectively modulate the assembly of luminescent lanthanide-benzenedicarboxylate nanostructures. Fluorescence studies demonstrate that the reaction rate can be customised by varying the anion transporter concentration, which dictates the rate of entry of the carboxylate ligand. Changes in the morphology of the liposome nanoreactors due to the assisted transmembrane transport of benzenedicarboxylate were investigated using cryo-TEM and time-resolved SAXS measurements, which revealed a structural transformation of the lipid bilayer during the complex formation. Our findings provide a novel platform for exploring coordination chemistry in nanoscale confinements, opening avenues for the design of biohybrid materials.

Fourteen diterpenes were isolated from methanol extracts of the aerial parts of Coleus comosus,Coleus forsteri "Marginatus", and Plectranthus ciliatus. The compounds belong to the abietane (1-4, 9-11, and 13), ent-clerodane (5-8), and ent-kaurane (14, 15) classes. Three new compounds were isolated from C. comosus, including 3-O-acetylornatin G (2), 3,12-di-O-acetylornatin G (3), ornatin B methyl ester (5), and ornatin F (4), for which we proposed a revised structure. The structures of the compounds were determined by comprehensive spectroscopic data analysis. The isolated diterpenes were examined in silico for their physicochemical and early ADME properties. Their antiproliferative effects were determined in vitro using human breast (MDA-MB-231 and MCF-7), cervical (HeLa), and glioblastoma (U-87 MG) cancer cell lines. The royleanone- and hydroquinone-type abietane diterpenes (9-13)exhibited the most potent antiproliferative activity against all cancer cell lines tested, particularly against glioblastoma cells, with IC50 values ranging from 1.1 to 15.6 mu M.

Nature uses various chiral and unsymmetric building blocks to form substantial and complex supramolecular assemblies. In contrast, the majority of organic ligands used in metallosupramolecular chemistry are symmetric and achiral. Here we extend the group of unsymmetric chiral bile acids used as a scaffold for organic bispyridyl ligands by employing chenodeoxycholic acid (CDCA), an epimer of the previously used ursodeoxycholic acid (UDCA). The epimerism, flexibility, and bulkiness of the ligands leads to large structural differences in coordination products upon reaction with Pd(NO3)2. The UDCA-bispyridyl ligand self-assembles quantitatively into a single crown-like Pd3L6 complex, whereas the CDCA ligand provides a mixture of coordination complexes of general formula PdnL2n, i.e., Pd2L4, Pd3L6, Pd4L8, Pd5L10, and even Pd6L12 containing an impressive 120 chiral centers. The coordination products were studied by a combination of analytical methods, with ion-mobility mass spectrometry (IM-MS) providing valuable details on their structure and allowed an effective separation of m/z 1461 to individual signals according to the arrival time distribution, thereby revealing four different ions of [Pd3L6(NO3)3]3+, [Pd4L8(NO3)4]4+, [Pd5L10(NO3)5]5+, and [Pd6L12(NO3)6]6+. The structures of all the complexes were modelled using DFT calculations. Finally, the challenges and conclusions in determining the specific structural identity of these unsymmetric species are discussed.

Schisandra chinensis (Schisandraceae) is a medicinal plant widely used in traditional Chinese medicine. Under the name Wu Wei Zi, it is used to treat many diseases, especially as a stimulant, adaptogen, and hepatoprotective. Dibenzocyclooctadiene lignans are the main compounds responsible for the effect of S. chinensis. As a part of ongoing studies to identify and evaluate anti-inflammatory natural compounds, we isolated a series of dibenzocyclooctadiene lignans and evaluated their biological activity. Furthermore, we isolated new sesquiterpene 7,7-dimethyl-11-methylidenespiro[5.5]undec-2-ene-3-carboxylic acid. Selected dibenzocyclooctadiene lignans were tested to assess their anti-inflammatory potential in LPS-stimulated monocytes by monitoring their anti-NF-κB activity, antioxidant activity in CAA assay, and their effect on gap junction intercellular communication in WB-ras cells. Some S. chinensis lignans showed antioxidant activity in CAA mode and affected the gap junction intercellular communication. The anti-inflammatory activity was proven for (−)-gomisin N, (+)-γ-schisandrin, rubrisandrin A, and (−)-gomisin J.

Nuclear magnetic resonance (NMR) spectroscopy of paramagnetic systems is an advancing field that contributes to characterization of the structure and magnetism of molecules, molecular assemblies, biomolecules, and materials. In this account, we utilize the hyperfine field intrinsic to ruthenium(III) coordination compounds to uncover details of their supramolecular host-guest binding with cyclodextrins. We interpret perturbations of the 1H NMR shifts of the host to suggest the binding mode of the interaction. We demonstrate how the size of the cyclodextrin cavity and the structural modification of the guest affect whether the binding occurs through a head or tail portal of the cyclodextrin and attempt to explain the observed differences in terms of molecular shapes and the charge-distribution complementarity between the host and guest. Paramagnetic NMR spectroscopy of host-guest systems is shown to be a useful tool for supramolecular and structural chemists investigating modes of molecular encapsulation.

Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and biomedicine. This work provides a systematic review on their transport processes within the enterohepatic circulation and related processes. The focus is laid on the description of specific or less-specific BA transport proteins and their localization. Initially, the reader is provided with essential information about BAs′ properties, their systemic flow, metabolism, and functions. Later, the transport processes are described in detail and schematically illustrated, moving step by step from the liver via bile ducts to the gallbladder, small intestine, and colon; this description is accompanied by descriptions of major proteins known to be involved in BA transport. Spillage of BAs into systemic circulation and urine excretion are also discussed. Finally, the review also points out some of the less-studied areas of the enterohepatic circulation, which can be crucial for the development of BA-related drugs, prodrugs, and drug carrier systems.

Construction of structurally complex architectures using inherently chiral, asymmetric, or multi-heterotopic ligands is a major challenge in metallosupramolecular chemistry. Moreover, the hierarchical self-organization of such complexes is unique. Here, we introduce a water-soluble, facially amphiphilic, amphoteric, chiral, asymmetric, and hetero-tritopic ligand derived from natural bile acid, ursodeoxycholic acid. We show that via the supramolecular transmetalation reaction, using nitrates of Cu(II) or Fe(III), and subsequently Pd(II), a superchiral Pd3L6 complex can be obtained. Even though several possible constitutional isomers of Pd3L6 could be formed, because of the ligand asymmetry and relative flexibility of carbamate-pyridyl moieties attached to the steroid scaffold, only a single product with C-3 rotational symmetry was obtained. Finally, we demonstrate that these amphiphilic complexes can self organize into hexagonal microparticles in aqueous media. This finding may lead to the development of novel self-assembled metal-organic functional materials made of natural, abundant, and relatively inexpensive steroidal compounds.

Native and synthetically modified cyclodextrins (CDs) are useful building blocks in the construction of large coordination complexes and porous materials with various applications. Sandwich-type complexes (STCs) are one of the important groups in this area. Usually, coordination of secondary hydroxyls or the "head" portal of native CD molecules to a notional multinuclear ring of metal cations leads to formation of head-to-head STCs. Our study introduces a new CD ligand, hexakis(2,3-diO-methyl)-alpha-cyclodextrin, which enables formation of not only intriguing head-to-head but also novel tail-to-tail STCs. Homometallic silver-based head-to-head STCs, AgPF6-STC and AgClO4-STC, were obtained by coordination of ligand methoxy groups to six Ag+, while bulky counteranions are not only located on the outside but also fill the inner space of the infinite linear channels formed. In contrast, the unique homometallic tail-to-tail RbF-STC was prepared by complexation of primary hydroxyls, "tails", to 12 Rb+ cations tightly interconnected by 12 F- anions, creating a complex structure with accessible pores for potential gas adsorption.

Recent work has identified a bis-(p-nitrophenyl)ureidodecalin anion carrier as a promising candidate for biomedical applications, showing good activity for chloride transport in cells yet almost no cytotoxicity. To underpin further development of this and related compounds, a detailed structural and binding investigation is reported. Crystal structures of the transporter as five solvates confirm the diaxial positioning of urea groups while revealing a degree of conformational flexibility. Structures of complexes with Cl-, Br-, NO3-, SO42- and AcO-, supported by computational studies, show how the binding site can adapt to accommodate these anions. (HNMR)-H-1 binding studies revealed exceptionally high affinities for anions in DMSO, decreasing in the order SO42->H2PO4-approximate to HCO3-approximate to AcO->> HSO4->Cl->Br->NO3->I-. Analysis of the binding results suggests that selectivity is determined mainly by the H-bond acceptor strength of different anions, but is also modulated by receptor geometry.

Large, non-symmetrical, inherently chiral bispyridyl ligand (L) derived from natural ursodeoxycholic bile acid was used in coordination to square-planar tetravalent Pd(II) yielding the cationic enantiomer of Pd3L6 coordination complex (1) containing 60 well-defined chiral centers in its flower-like structure. Complex 1 can be readily transformed by addition of chloride into a smaller enantiomerically pure metallacycle Pd3L3Cl6 (2). This transformation is reversible and can be restored by the addition of silver cations. Furthermore, a mixture of two constitutional isomers of the trimer, 2 and 2’, can be obtained by direct coordination of L to trans-N-pyridyl-coordinating Pd(II). These intriguing supramolecular assemblies have been thoroughly described by combination of various methods. The interconversion between particular species was followed by 1H NMR and mass spectrometry. The dimensions of complexes determined by 1H DOSY NMR spectroscopy and drift tube ion-mobility mass spectrometry agree well with molecular models. Variable temperature 1H NMR experiment was carried out to study the thermodynamic equilibria between 2 and 2’ complexes. The thermodynamic data obtained from the van’t Hoff plot agree well with computational calculations.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

The enhancement of the binding between halide anions and a Lewis acidic uranyl-salophen receptor has been achieved by the introduction of pendant electron-deficient arene units into the receptor skeleton. The association and the occurrence of the elusive anion-pi interaction with halide anions (as tetrabutylammonium salts) have been demonstrated in solution and in the solid state, providing unambiguous evidence on the interplay of the concerted interactions responsible for the anion binding.

The enhancement of the binding between halide anions and a Lewis acidic uranyl-salophen receptor has been achieved by the introduction of pendant electron-deficient arene units into the receptor skeleton. The association and the occurrence of the elusive anion-π interaction with halide anions (as tetrabutylammonium salts) have been demonstrated in solution and in the solid state, providing unambiguous evidence on the interplay of the concerted interactions responsible for the anion binding.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.