Self-Assembly of a Water-Soluble Pd16 Square Bicupola Architecture and Its Use in Aerobic Oxidation in Aqueous Medium.

Designing supramolecular architectures with uncommon geometries has always been a key goal in the field of metal-ligand coordination-driven self-assembly. It acquires added significance if functional building units are employed in constructing such architectures for fruitful applications. In this report, we address both these aspects by developing a water-soluble Pd16L8 coordination cage 1 with an unusual square orthobicupola geometry, which was used for selective aerobic oxidation of aryl sulfides. Self-assembly of a benzothiadiazole-based tetra-pyridyl donor L with a ditopic cis-[(tmeda)Pd(NO3)2] acceptor [tmeda = N,N,N',N'-tetramethylethane-1,2-diamine] produced 1, and the geometry was determined by single-crystal X-ray diffraction study. Unlike the typically observed tri- or tetrafacial barrel, the present Pd16L8 coordination assembly features a distinctive structural topology and is a unique example of a water-soluble molecular architecture with a square orthobicupola geometry. Efficient and selective aerobic oxidation of sulfides to sulfoxides is an important challenge as conventional oxidation generally leads to the formation of sulfoxide along with toxic sulfone. Cage 1, designed with a ligand containing a benzothiadiazole moiety, demonstrates an ability to photogenerate reactive oxygen species (ROS) in water, thus enabling it to serve as a potential photocatalyst. The cage showed excellent catalytic efficiency for highly selective conversion of alkyl and aryl sulfides to their corresponding sulfoxides, therefore without the formation of toxic sulfones and other byproducts, under visible light in aqueous medium.

Pyrrole ßC-B-N Fused Porphyrins: Molecular Structures and Opto-Electrochemical Studies.

Herein, we report the design, synthesis, structure, and electrochemical study of doubly ßC-B-N fused Ni(II) porphyrins (1-trans, 1-cis, 2-trans, and 2-cis). These compounds have been synthesized from A2B2 type dipyridyl Ni(II) porphyrins (Ar=Ph for 1 a; Ar=C6F5 for 2 a) via Lewis base-directed electrophilic aromatic borylation reactions. The solution state structures of these compounds have been established using 1H NMR, 11B NMR, 1H-1H COSY, 1H-13C HSQC, and 19F-13C HSQC NMR techniques. Single crystal X-ray analysis have revealed that 1-trans, 1-cis, and 2-trans adopt ruffled conformations, with alternate meso-carbons on the opposite sides of the mean porphyrin plane. The Soret bands in the absorption spectra of the B-N fused molecules are ~40 nm redshifted compared to unfused Ni(II) porphyrin precursors. The B-N fusion have diminished the redox potential of fused porphyrins. Although 1-trans and 1-cis, show four oxidation processes, 2-trans and 2-cis show only three oxidation processes. DFT studies have revealed that the tetrahedral geometry of the boron has induced a twist in the π-conjugation, which destabilizes the HOMO and stabilizes the LUMO in 1-trans, 1-cis, 2-trans, and 2-cis.

Chirality Sensing of Cryptochiral Guests with Prism[n]arenes.

Optical chirality sensing has gained significant attention in recent years. Within this field, the quest for stereodynamic chiroptical probes capable of detecting cryptochiral guests presents a formidable challenge. Macrocycles exhibiting planar chirality have emerged as promising candidates for amplifying the chirality of cryptochiral guests. In this study, we demonstrate that the formation of host-guest complexes between cryptochiral molecules and planar chiral prismarenes triggers electronic circular dichroism (ECD) signals via host-guest complexation-induced chirality amplification. The absolute configuration of the most stable chiral macrocyclic host-guest complex has been established by resorting to both exciton model and DFT computations. Furthermore, we demonstrated that this supramolecular chirality sensing system can be employed to determine the enantiomeric composition of scalemic mixtures by measuring the ECD bands intensity. The information described here opens the way for the use of prismarenes as stereodynamic probes for sensing of cryptochiral guests.

Analysis of the crystal structure of a parallel three-stranded coiled coil.

Here, we present the crystal structure of the synthetic peptide KE1, which contains four K-coil heptads separated in the middle by the QFLMLMF heptad. The structure determination reveals the presence of a canonical parallel three stranded coiled coil. The geometric characteristics of this structure are compared with other coiled coils with the same topology. Furthermore, for this topology, the analysis of the propensity of the single amino acid to occupy a specific position in the heptad sequence is reported. A number of viral proteins use specialized coiled coil tail needles to inject their genetic material into the host cells. The simplicity and regularity of the coiled coil arrangement made it an attractive system for de novo design of key molecules in drug delivery systems, vaccines, and therapeutics.

Cavity-Shape-Dependent Divergent Chemical Reaction inside Aqueous Pd6L4 Cages.

Chemical reactions inside the confined pockets of enzyme-mimicking hosts, such as cages and macrocycles, have been an emerging field of interest over the past decade. Although many such reactions are known, the use of such cages toward the divergent synthesis of nonisomeric products has not been well explored. Divergent synthesis is a technique of forming two or more distinct products from the same reagents by changing the catalyst or reaction conditions. Changing the shape of the cage can also change the nature and magnitude of the host-guest interactions. Thus, is it possible for such changes to cause differences in the reaction pathways leading to formation of nonisomeric products? Herein, we report a divergent chemical transformation of anthrone [anthracen-9(10H)-one] inside different water-soluble M6L4 cages. When anthrone was encapsulated inside a newly synthesized M6L4 octahedral cage 1, it dimerized to form dianthrone [9,9'-bianthracen-10,10'(9H,9'H)-dione]. In contrast, when the same chemical reaction was performed inside a M6L4 double-square shaped cage 2, it was oxidized to form anthraquinone [anthracene-9,10-dione]. Similar results were obtained with a different set of isomeric aqueous Pd6 cages 3a (octahedral cage) and 3b (double-square cage), indicating the dependence of the shape of cavity on the divergent synthesis. The present report demonstrates a unique example of different outcomes/results of a reaction depending on the shape of the molecular container, which was driven by the host-guest interactions and the preorganization of the substrates.

Confused-Prism[5]arene: a Conformationally Adaptive Host by Stereoselective Opening of the 1,4-Bridged Naphthalene Flap.

The confused-prism[5]arene macrocycle (c-PrS[5]Me ) shows conformational adaptive behavior in the presence of ammonium guests. Upon guest inclusion, the 1,4-bridged naphthalene flap reverses its planar chirality from pS to pR (with reference to the pS(pR)4 enantiomer). Stereoselective directional threading is also observed in the presence of directional axles, in which up/down stereoisomers of homochiral (pR)5 -c-PrS[5]Me pseudorotaxanes are formed.

Water-Soluble Pd6L3 Molecular Bowl for Separation of Phenanthrene from a Mixture of Isomeric Aromatic Hydrocarbons.

Phenanthrene is a high-value raw material in chemical industries. Separation of phenanthrene from isomeric anthracene continues to be a big challenge in the industry due to their very similar physical properties. Herein, we report the self-assembly of a water-soluble molecular bowl (TB) from a phenothiazine-based unsymmetrical terapyridyl ligand (L) and a cis-blocked 90° Pd(II) acceptor. TB featured an unusual bowl-like topology, with a wide rim diameter and a hydrophobic inner cavity fenced by the aromatic rings of the ligand. The above-mentioned features of TB allow it to bind polyaromatic hydrocarbons in its confined cavity. TB shows a higher affinity for phenanthrene over its isomer anthracene in water, which enables it to separate phenanthrene with ∼93% purity from an equimolar mixture of phenanthrene and anthracene. TB is also able to extract pyrene with around ∼90% purity from an equimolar mixture of coronene, perylene, and pyrene. Moreover, TB can be reused for several cycles without significant degradation in its performance as an extracting agent. This clean strategy of separation of phenanthrene and pyrene from a mixture of hydrophobic hydrocarbons by aqueous extraction is noteworthy.

Solvent Induced Conversion of a Self-Assembled Gyrobifastigium to a Barrel and Encapsulation of Zinc-Phthalocyanine within the Barrel for Enhanced Photodynamic Therapy.

A rare gyrobifastigium architecture (GB) was constructed by self-assembly of a tetradentate donor (L) with PdII acceptor in DMSO. The GB was converted to its isomeric tetragonal barrel (MB) upon treatment with water. The hydrophobic cavity of MB has been explored for the encapsulation of zinc-phthalocyanine (ZnPc), which is an excellent photosensitizer for photodynamic therapy (PDT). However, the poor water-solubility and aggregation tendency are the main reasons for the suboptimal PDT performance of free ZnPc in the aqueous medium. Effective solubilization of ZnPc in an aqueous medium was achieved by encapsulating it in the cavity of MB. The inclusion complex (ZnPc⊂MB) showed enhanced singlet oxygen generation in water. Higher cellular uptake and anticancer activity of the ZnPc⊂MB compared to free ZnPc on HeLa cells indicate that encapsulation of ZnPc in an aqueous host is a potential strategy for enhancement of its PDT activity in water.

Encapsulation of Trimethine Cyanine in Cucurbit[8]uril: Solution versus Solid-State Inclusion Behavior.

Inclusion of polymethine cyanine dyes in the cavity of macrocyclic receptors is an effective strategy to alter their absorption and emission behavior in aqueous solution. In this paper, the effect of the host-guest interaction between cucurbit[8]uril (CB[8]) and a model trimethine indocyanine (Cy3) on dye spectral properties and aggregation in water is investigated. Solution studies, performed by a combination of spectroscopic and calorimetric techniques, indicate that the addition of CB[8] disrupts Cy3 aggregates, leading to the formation of a 1 : 1 host-guest complex with an association constant of 1.5×106  M-1 . At concentrations suitable for NMR experiments, the slow formation of a supramolecular polymer was observed, followed by precipitation. Single crystals X-ray structure elucidation confirmed the formation of a polymer with 1 : 1 stoichiometry in the solid state.

Vitamin B12 in Foods, Food Supplements, and Medicines-A Review of Its Role and Properties with a Focus on Its Stability.

Vitamin B12, also known as the anti-pernicious anemia factor, is an essential micronutrient totally dependent on dietary sources that is commonly integrated with food supplements. Four vitamin B12 forms-cyanocobalamin, hydroxocobalamin, 5'-deoxyadenosylcobalamin, and methylcobalamin-are currently used for supplementation and, here, we provide an overview of their biochemical role, bioavailability, and efficacy in different dosage forms. Since the effective quantity of vitamin B12 depends on the stability of the different forms, we further provide a review of their main reactivity and stability under exposure to various environmental factors (e.g., temperature, pH, light) and the presence of some typical interacting compounds (oxidants, reductants, and other water-soluble vitamins). Further, we explore how the manufacturing process and storage affect B12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B12 products on the market. We also provide an overview of the approaches toward their stabilization, including minimization of the destabilizing factors, addition of proper stabilizers, or application of some (innovative) technological processes that could be implemented and contribute to the production of high-quality vitamin B12 products.

Conventional vs. Microwave- or Mechanically-Assisted Synthesis of Dihomooxacalix[4]arene Phthalimides: NMR, X-ray and Photophysical Analysis.

Direct O-alkylation of p-tert-butyldihomooxacalix[4]arene (1) with N-(bromopropyl)- or N-(bromoethyl)phthalimides and K2CO3 in acetonitrile was conducted under conventional heating (reflux) and using microwave irradiation and ball milling methodologies. The reactions afforded mono- and mainly distal di-substituted derivatives in the cone conformation, in a total of eight compounds. They were isolated by column chromatography, and their conformations and the substitution patterns were established by NMR spectroscopy (1H, 13C, COSY and NOESY experiments). The X-ray structures of four dihomooxacalix[4]arene phthalimide derivatives (2a, 3a, 3b and 5a) are reported, as well as their photophysical properties. The microwave (MW)-assisted alkylations drastically reduced the reaction times (from days to less than 45 min) and produced higher yields of both 1,3-di-substituted phthalimides (3a and 6a) with higher selectivity. Ball milling did not reveal to be a good method for this kind of reaction.

Prismarenes: A New Class of Macrocyclic Hosts Obtained by Templation in a Thermodynamically Controlled Synthesis.

The novel title macrocycles, based on methylene-bridged 1,5-naphthalene units, have been obtained by template effect in a thermodynamically controlled synthesis. In detail, the prism[5]arene 1 or the prism[6]arene 3 was selectively removed from the equilibrium mixture by using the complementary ammonium-templating agent. When only the solvent 1,2-DCE was used, the 1,4-confused derivative 2 was obtained. The prism[5]arene here described shows a deep π-electron-rich aromatic cavity that exhibits a great affinity for the quaternary ammonium guests, originating from favorable cation···π and +NC-H···π interactions. This recognition motif is the basis of the templated synthesis of the prism[n]arenes here reported.

Influence of exo-Adamantyl Groups and endo-OH Functions on the Threading of Calix[6]arene Macrocycle.

Calix[6]arenes bearing adamantyl groups at the exo-rim form pseudorotaxanes with dialkylammonium axles paired to the weakly coordinating [B(ArF)4]- anion. The exo-adamantyl groups give rise to a more efficient threading with respect to the exo-tert-butyl ones, leading to apparent association constants more than one order of magnitude higher. This improved stability has been ascribed to the more favorable van der Waals interactions of exo-adamantyls versus exo-tert-butyls with the cationic axle. Calix[6]arenes bearing endo-OH functions give rise to a less efficient threading with respect to the endo-OR ones, in line with what was known from the complexation of alkali metal cations.

Synthesis, Crystal Structure, and Biological Activity of a Multidentate Calix[4]arene Ligand Doubly Functionalized by 2-Hydroxybenzeledene-Thiosemicarbazone.

The design and synthesis of a novel tert-butyl-calix[4]arene functionalized at 1, 3 positions of the lower rim with two terminal 2-hydroxybenzeledene-thiosemicarbazone moieties is reported. The new ligand with multi-dentate chelating properties was fully characterized by several techniques: ESI-Mass spectroscopy, FT-IR, 1H-NMR, and single crystal X-ray diffraction. The solid state structure confirms that the calix[4]arene macrocycle has the expected open cone conformation, with two opposite phenyl rings inclined outwards with large angles. The conformation of the two alkoxythiosemicarbazone arms produces a molecule with a C2 point group symmetry. An interesting chiral helicity is observed, with the two thiosemicarbazone groups oriented in opposite directions like a two-blade propeller. A water molecule is encapsulated in the center of the two-blade propeller through multiple H-bond coordinations. The antibacterial, antifungal, anticancer, and cytotoxic activities of the calix[4]arene-thiosemicarbazone ligand and its metal derivatives (Co2+, Ni2+, Cu2+, and Zn2+) were investigated. A considerable antibacterial activity (in particular against E. coli, MIC, and MBC = 31.25 µg/mL) was observed for the ligand and its metal derivatives. Significant antifungal activities against yeast (C. albicans) were also observed for the ligand (MIC = 31.25 µg/mL and MBC = 125 µg/mL) and for its Co2+ derivative (MIC = 62.5 µg/mL). All compounds show cytotoxicity against the tested cancerous cells. For the Saos-2 cell line, the promising anticancer activity of ligand L (IC50 < 25 µg/mL) is higher than its metal derivatives. The microscopic analysis of DAPI-stained cells shows that the treated cells change in morphology, with deformation and fragmentation of the nuclei. The hemo-compatibility study demonstrated that this class of compounds are suitable candidates for further in vivo investigations.

Dihomooxacalix[4]arene-Based Fluorescent Receptors for Anion and Organic Ion Pair Recognition.

Fluorescent dihomooxacalix[4]arene-based receptors 5a-5c, bearing two naphthyl(thio)ureido groups at the lower rim via a butyl spacer, were synthesised and obtained in the cone conformation in solution. The X-ray crystal structures of 1,3- (5a) and 3,4-dinaphthylurea (5b) derivatives are reported. Their binding properties towards several anions of different geometries were assessed by 1H-NMR, UV-Vis absorption and fluorescence titrations. Structural and energetic insights of the naphthylurea 5a and 5b complexes were also obtained using quantum mechanical calculations. The data showed that all receptors follow the same trend, the association constants increase with the anion basicity, and the strongest complexes were obtained with F-, followed by the oxoanions AcO- and BzO-. Proximal urea 5b is a better anion receptor compared to distal urea 5a, and both are more efficient than thiourea 5c. Compounds 5a and 5b were also investigated as heteroditopic receptors for biologically relevant alkylammonium salts, such as the neurotransmitter γ-aminobutyric acid (GABA·HCl) and the betaine deoxycarnitine·HCl. Chiral recognition towards the guest sec-butylamine·HCl was also tested, and a 5:2 selectivity for (R)-sec-BuNH3+·Cl- towards (P) or (M) enantiomers of the inherently chiral receptor 5a was shown. Based on DFT calculations, the complex [(S)-sec-BuNH3+·Cl-/(M)-5a] was indicated as the more stable.

Synthesis, Characterization, and Solid-State Structure of [8]Cycloparaphenylenes with Inherent Chirality.

We report here the synthesis of two [8]cycloparaphenylenes ([8]CPP) derivatives, 1 and 2, bearing a monosubstituted benzene moiety. The presence of the substituent implies a planar chirality for the monosubstituted [8]CPP 1 and 2, whose configuration is here described by applying the chirality descriptors pR and pS. Experimental evidence of this planar chirality has been obtained through 1H VT NMR studies and by addition of Pirkle's reagent. This was confirmed by the X-ray crystal structure of 2, which represents an interesting example of solid-state structure of a monosubstituted [8]CPP derivative. Derivative 2 crystallizes in two monoclinic crystal forms (α and ß), which show a herringbone motif. The [8]CPP ring of the α form encapsulates two dichloromethane molecules, held through C-H···π interactions, while in the ß form, open channels are partially filled by highly disordered solvent molecules.

Threading of Conformationally Stable Calix[6]arene Wheels Substituted at the Methylene Bridges.

Calix[6]arenes disubstituted at the methylene bridges, which are stable in the cone or 1,2,3-alternate conformation, form pseudorotaxanes with dialkylammonium axles. The cone wheel-based pseudorotaxanes are 10-100 times more stable than those obtained with the native conformationally mobile calix[6]arene wheel, as a consequence of their higher degree of preorganization. The threading of conformationally stable 1,2,3-alternate calix[6]arenes is unprecedented in the literature. Therefore, very peculiar NMR features are here evidenced for this threading process involving the less symmetrical 1,2,3-alternate calix[6]arene conformation, which implies a peculiar rototranslation motion of the axle.

A Simple Tetraminocalix[4]arene as a Highly Efficient Catalyst under "On-Water" Conditions through Hydrophobic Amplification of Weak Hydrogen Bonds.

The simple tetraminocalix[4]arene 1, which contains weak H-bond-donor NH2 groups, is reported to be a highly efficient organocatalyst for the Vinylogous Mukaiyama Aldol Reaction (VMAR) of 2-(trimethylsilyloxy)furan 5 with α-ketoesters 6 a-l under "on-water" conditions owing to the hydrophobic amplification of weak H-bond interactions. The catalytic efficiency of calixarene catalyst 1 was shown to be closely related to its recognition abilities towards the reactants 5 and 6 through a multipoint recognition model. The proposed model provided good explanations for the differences on the reaction rate acceleration and on the stereoselectivity observed with different substrates.

Selective Binding of Spherical and Linear Anions by Tetraphenyl(thio)urea-Based Dihomooxacalix[4]arene Receptors.

Three novel tetra(thio)ureido dihomooxacalix[4]arene anion receptors (phenylurea 4a, phenylthiourea 4b, and tert-butylurea 4c) were synthesized and obtained in the cone conformation in solution, as shown by NMR studies. The X-ray crystal structure of 4c is reported. The host-guest properties of these receptors toward several anions were investigated by 1H NMR titrations. Phenylurea 4a displayed a very efficient binding toward the spherical F- and Cl- anions, and the linear CN- (log Kass = 3.46, 3.50, and 4.02, respectively). In comparison to related bidentate phenylurea dihomooxacalix[4]arenes, tetraphenylurea 4a is more preorganized and the higher number of hydrogen bond donor sites provides a remarkable enhancement of its binding efficiency.

A general exit strategy of monoheme cytochromes c and c2 in electron transfer complexes?

Using our previously reported maps of the electrostatic surface of horse heart ferri- and ferro-cyt c, comparisons were made between the complementary electrostatic surfaces of three cyt c peroxidase-cyt c complexes and the photosynthetic reaction center-cyt c complex, considering both iron oxidation states. The results obtained were consistent with a sliding mechanism for the electron shuttle on the surface of the protein complexes, promoted by the change in iron oxidation state. This mechanism was found to be in agreement with theoretical and NMR studies reported in the literature. Importantly, the analysis also provided a rationale for recognition of nonproductive associations. As we have previously reported the same conclusion on examination of redox partners of cyt c in the mitochondrial respiratory pathway, our hypothesis is that the proposed mechanism could represent a general exit strategy of monoheme cyts c and c2 in electron transfer complexes.