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The fluorescence of functional dyes was generally quenched in aqueous solution, which hindered their application in water-bearing detections. In this work, a novel strategy based on host-guest interaction was provided for the purpose of fluorescence enhancement in aqueous solution and cell imaging. Three adamantane-modified fluorescent dyes (Coum-Ad, NP-Ad, NR-Ad) with coumarin, 1,8-naphthalimide and Nile Red as fluorophores were initially designed and prepared. The ((adamantan-1-yl)methyl)amino group, as the auxochrome of those dyes, complexed with methylated β-cyclodextrin (M-β-CD) via supramolecular interaction, and then fluorescent supramolecular nanoparticles (FSNPs) were formed by self-assembly in water. The inclusion equilibrium constant (K) could be as high as 3.94×10 4  M -1 . With the addition of M-β-CD, fluorescence quantum yields of these dyes were separately improved to 69.8 %, 32.9 % and 41.3 %. Inspired by the above satisfactory results, six adamantane-modified probes organelle-NPAds with organelle-targeting capability were further obtained. As the formation of hydrogen bonds between organelle-NPAd2 and M-β-CD verified by theoretical calculation, K of organelle-NPAd2 (5.13×10 4  M -1 ~4.53×10 5  M -1 ) with M-β-CD was higher than that of organelle-NPAd1 (1.15×10 4  M -1 ~3.66×10 4  M -1 ) and their fluorescence quantum yields increased to 32.8 %~83.6 % in aqueous solution. In addition, fluorescence enhancement was realized in cell imaging with the addition of M-β-CD., (© 2023 Wiley-VCH GmbH.)

The integration of microscopic hydrogels with high specific surface area and physically reactive groups into microfluidic systems for selective molecular interactions is attracting increasing attention. Herein, the reversible capture and release of molecules through host-guest interactions of hydrogel dots in a microfluidic device is reported, which translates the supramolecular chemistry to the microscale conditions under continuous flow. Polyacrylamide (PAAm) hydrogel arrays with grafted β-cyclodextrin (β-CD)  modified poly(2-methyl-2-oxazoline) (CD-PMOXA) chains are fabricated by photopolymerization and integrated into a polydimethylsiloxane (PDMS)-on-glass chip. The β-CD/adamantane (β-CD/Ada) host-guest complex is confirmed by two dimensional Nuclear Overhauser Effect Spectroscopy NMR (2D NOESY NMR) prior to transfer to microfluidics. Ada-modified molecules are successfully captured by host-guest interaction formed between the CD-PMOXA grafted chains in the hydrogel network and the guest molecule in the solution. Furthermore, the captured molecules are released by perfusing free β-CD with higher binding affinity than those grafted in the hydrogel array. A small guest molecule adamantane-fluorescein-isothiocyanate (Ada-FITC) and a macromolecular guest molecule (Ada-PMOXA-Cyanine 5 (Cy5)) are separately captured and released for three times with a release ratio up to 46% and 92%, respectively. The reproducible capture and release of functional molecules with different sizes demonstrates the stability of this hydrogel system in microfluidics and will provide an opportunity for future applications., (© 2023 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)

In a recent publication, Eleftheriou et al. proposed that inhibitors of dipeptidyl peptidase-4 (DPP-4) are functional inhibitors of the main protease (M pro ) of SARS-CoV-2. Their predictions prompted the authors to suggest linagliptin, a DPP-4 inhibitor and approved anti-diabetes drug, as a repurposed drug candidate against the ongoing COVID-19 pandemic. We used an enzymatic assay measuring the inhibition of M pro catalytic activity in the presence of four different commercially available gliptins (linagliptin, sitagliptin, alogliptin and saxagliptin) and several structural analogues of linagliptin to study the binding of DPP-4 inhibitors to M pro and their functional activity. We show here that DPP-4 inhibitors like linagliptin, other gliptins and structural analogues are inactive against M pro ., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

An organoruthenium(II) complex with pyrithione (2-mercaptopyridine N-oxide) 1 a has previously been identified by our group as a compound with promising anticancer potential without cytotoxicity towards non-cancerous cells. To expand the rather limited research on compounds of this type, an array of novel chlorido and 1,3,5-triaza-7-phosphaadamantane (pta) organoruthenium(II) complexes with methyl-substituted pyrithiones has been prepared. After thorough investigation of the aqueous stability of these complexes, their modes of action have been elucidated at the cellular level. Minor structural alterations in the ruthenium-pyrithionato compounds resulted in fine-tuning of their cytotoxicities. The best performing compounds, 1 b and 2 b, with a chlorido or pta ligand bound to ruthenium, respectively, and a methyl group at the 3-position of the pyrithione scaffold, have been further investigated. Both compounds trigger early apoptosis, induce the generation of reactive oxygen species and G1 arrest in A549 cancer cells, and show no strong interaction with DNA. However, only 1 b also inhibits thioredoxin reductase. Wound healing assays and mitochondrial function evaluation have revealed differences between these two compounds at the cellular level., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Adamantyl vinyl ketone (AVK) and its copolymers are synthesized using reversible addition fragmentation chain-transfer (RAFT) methodology and then degraded using UV light. The polymerization of AVK is found to be controlled as indicated by a linear correlation between the molecular weights of the polymers produced and monomer conversion as well as a series of chain extensions. The RAFT method is also used to synthesize random and block copolymers of AVK and methyl methacrylate. Irradiating poly(adamantyl vinyl ketone) (PAVK) with UV light affords a polyolefin and adamantane as the major products. Similar products are obtained, along with poly(methyl methacrylate) (PMMA), when the block copolymer is subjected to UV light. The random copolymer undergoes complete degradation under similar conditions. A mechanism wherein stereoelectronic effects channel photodegradation through Norrish I Type pathways in a manner that preserves the main chain of the polymer during the decomposition process is proposed., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The synthesis and pharmacological evaluation of C1-substituted adamantane hydrazones, their C2-substituted isomers, and C1-substituted adamantane furanoic carboxamides is described. These new adamantane derivatives exhibited an interesting pharmacological profile in terms of trypanocidal activity and selectivity. The most active adduct with the best selectivity in this study was found to be the phenylacetoxy hydrazone 1 b (2-[4-(tricyclo[3.3.1.1 3,7 ]dec-1-yl)phenyl]-N'-[(5-nitrofuran-2-yl)methylene]acetohydrazide; EC 50 =11±0.9 nm, SI Tb =770)., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multivalency can facilitate complex formation when monovalent receptor-ligand interactions are weak. However, enhanced binding of two multivalent binding partners should be avoidable, for example when bivalent receptors ought to utilize multimolecular interactions to cross-link binding partners. We herein report the first systematic study to assess the criteria deciding whether a bivalent system engages in bivalency-enhanced interactions or cross-linking. We used DNA-instructed self-assembly to arrange the cucurbit[7]uril-adamantane host-guest system in 70-360 Å distance. Measurements and statistical mechanics analyses revealed that the affinity gain is controlled by 1) the distance between recognition modules, 2) the scaffold flexibility, and, importantly, 3) the strength of the monovalent interaction. We show that the bivalency effect can extend beyond 150 Å and discuss how, on the contrary, weak monovalent interactions reduce the concentration threshold for cross-linking. The findings are of interest for inhibitor design., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by β-cyclodextrin and γ-cyclodextrin (β-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host-guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with β-CD. We found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantane as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host-guest association: adamantane showed lower agglutination than di- or triamantane with β-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Formulating pharmaceutically active ingredients for drug delivery is a challenge. There is a need for new drug delivery systems that take up therapeutic molecules and release them into biological systems. We propose a novel mode of encapsulation that involves matrices formed through co-assembly of drugs with adamantane hybrids that feature four CG dimers as sticky ends. Such adamantanes are accessible via inexpensive solution-phase syntheses, and the resulting materials show attractive properties for controlled release. This is demonstrated for two different hybrids and a series of drugs, including anticancer drugs, antibiotics, and cyclosporin. Up to 20 molar equivalents of active pharmaceutical ingredients (APIs) are encapsulated in hybrid materials. Encapsulation is demonstrated for DNA-binding and several non-DNA binding compounds. Nanoparticles were detected that range in size from 114-835 nm average diameter, and ζ potentials were found to be between -29 and +28 mV. Release of doxorubicin into serum at near-constant rates for 10 days was shown, demonstrating the potential for slow release. The encapsulation and release in self-assembling matrices of dinucleotide-bearing adamantanes appears to be broadly applicable and may thus lead to new drug delivery systems for APIs., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The reaction of nitroxyl radicals TEMPO (2,2',6,6'-tetramethylpiperidinyloxyl) and AZADO (2-azaadamantane-N-oxyl) with an iron(I) synthon affords iron(II)-nitroxido complexes ( Ar L)Fe(κ 1 -TEMPO) and ( Ar L)Fe(κ 2 -N,O-AZADO) ( Ar L=1,9-(2,4,6-Ph 3 C 6 H 2 ) 2 -5-mesityldipyrromethene). Both high-spin iron(II)-nitroxido species are stable in the absence of weak C-H bonds, but decay via N-O bond homolysis to ferrous or ferric iron hydroxides in the presence of 1,4-cyclohexadiene. Whereas ( Ar L)Fe(κ 1 -TEMPO) reacts to give a diferrous hydroxide [( Ar L)Fe] 2 (μ-OH) 2 , the reaction of four-coordinate ( Ar L)Fe(κ 2 -N,O-AZADO) with hydrogen atom donors yields ferric hydroxide ( Ar L)Fe(OH)(AZAD). Mechanistic experiments reveal saturation behavior in C-H substrate and are consistent with rate-determining hydrogen atom transfer., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A smart targeting drug delivery nanocarrier is successfully constructed based on phototriggered competition of host-guest interaction. The targeting motif, i.e., biotin is first concealed by β-cyclodextrin (β-CD) via host-guest interaction. When the nanoparticles are exposed to UV light, the cleavage of photosensitive groups results in the exposure of adamantane (Ad) groups initially located in the interior of nanoassemblies, and β-CDs capped on biotin ligands can be replaced by Ad because of the higher binding constant between Ad and β-CD than that between biotin and β-CD. The competition of host-guest interaction leads to the recovery of targeting capacity of biotin ligands on the nanocarriers. By virtue of photoregulation, the nanocarriers exhibit controllable ligand-receptor recognition, which is proved by flow cytometry, laser confocal microscopy, and cytotoxicity assay. This strategy has a potential to improve the selectivity and safety of targeting drug delivery systems., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Moisture or water has the advantages of being green, inexpensive, and moderate. However, it is challenging to endow water-induced shape memory property and self-healing capability to one single polymer because of the conflicting structural requirement of the two types of materials. In this study, this problem is solved through introducing two kinds of supramolecular interactions into semi-interpenetrating polymer networks (semi-IPNs). The hydrogen bonds function as water-sensitive switches, making the materials show moisture-induced shape memory effect. The host-guest interactions (β-cyclodextrin-adamantane) serve as both permanent phases and self-healing motifs, enabling further increased chain mobility at the cracks and self-healing function. In addition, these polyvinylpyrrolidone/poly(hydroxyethyl methacrylate-co-butyl acrylate) semi-IPNs also show thermosensitive triple-shape memory effect., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A kind of novel heterogeneous composite hydrogel with dynamic nanocrosslinkers is designed, which is built via the preorganized host-guest interaction on the surface of cellulose nanocrystals. The reversible β-cyclodextrin/adamantane conjunctions and their gradual dissociation on the nanocrystal-polymer interface guarantee the compressibility and stretchability of the composite hydrogels. While the sacrificed toughening mechanism can be rebuilt in the as-prepared hydrogels, it fails to be regenerated in the swollen hydrogels. This fact is originally due to the extreme mechanical contrast between rigid nanocrystals and the flexible polymer phase. This heterogeneity is largely amplified by the swelling process: polymer chains are prestretched between nanocrosslinkers and generate residual stress on the dynamic nanocrystal-polymer interface. Thus, this swelling-induced heterogeneity resists the reassociation of the sacrificed β-cyclodextrin/adamantane complexes. Furthermore, the unstable nanocrystal-polymer interface induces the crack propagate along the nanocrosslinker surface, which remarkably retards the crack propagation during the stretch., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A supramolecular carbohydrate sensor was prepared by self-assembly of unilamellar bilayer vesicles of amphiphilic β-cyclodextrin with a boronic acid-adamantane conjugate (PBA-AD), which binds strongly to β-cyclodextrin through host-guest interactions (K a ≈4×10 4  m -1 ), so the vesicle surface exhibits multiple boronic acid receptors for carbohydrates. The binding of diols to the functionalized vesicles was tested with alizarin red S (ARS) as a reporter dye by using fluorescence and UV/Vis spectroscopy. Analysis of the competitive binding of monosaccharides revealed pH-dependent (pH 7.4-10.1) binding constants in the range of 100-3000 m -1 for d-fructose and 5-400 m -1 for d-glucose. Interestingly, the self-assembled sensor showed fluorescence intensity enhanced by about fivefold and a binding affinity to the reporter dye increased by about eightfold in comparison to PBA-AD and ARS without vesicles. This is attributed to increased local concentration of ARS and PBA-AD on the surface of the vesicles. Detection of d-fructose and d-glucose was possible in the physiologically relevant range in dilute aqueous solution., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chemical proteomics relies primarily on click-chemistry-based protein labeling and biotin-streptavidin enrichment, but these techniques have inherent limitations. Enrichment of intracellular proteins using a totally synthetic host-guest complex is described, overcoming the problem associated with the classical approach. We achieve this by affinity-based protein labeling with a target-specific probe molecule conjugated to a high-affinity guest (suberanilohydroxamic acid-ammonium-adamantane; SAHA-Ad) and then enriching the labeled species using a cucurbit[7]uril bead. This method shows high specificity for labeled molecules in a MDA-MB-231 breast cancer cell lysate. Moreover, this method shows promise for labeling proteins in live cells., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, we report unusual four-center interactions in the novel cage-like phosphane, 1,4,7-triaza-9-phosphatricyclo[5.3.2.1(4,9) ]tridecane (CAP). This water-soluble ligand, the first example of a tris(homoadamantane) ring system, can be considered a macrocyclic homologue of the well-known PTA (1,3,5-triaza-7-phosphaadamantane). However, (31) P NMR spectroscopic anomalies of CAP follow those typical for the bi-/tricyclic atrane systems. Another atrane-like feature of CAP is the ability of one nitrogen atom to undergo out-in pyramidal inversion. The latter is associated with a substantial decrease in the intracage N-N and P-N distances. Analysis of electron density distribution [molecular electrostatic potential (MESP) and atoms-in-molecules (AIM) approaches] suggests that the P and N atoms in the pyramidally inverted CAP derivatives are involved in interactions resulting in accumulation of electron density at the center of the phosphane cage. The latter can reliably explain the stereoelectronic and NMR anomalies of the new ligand. The semi-flexible CAP cage populates the structural niche between the rigid adamantine skeleton of PTA and flexible atrane systems and can be regarded as an alternative to PTA in aqueous coordination chemistry., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The enantiomers of vildagliptin, an orally available and selective dipeptidyl-peptidase-4 inhibitor used for the treatment of type II diabetes, have been separated by CD-modified CZE, using uncoated fused-silica capillary. After screening 13 negatively charged CD derivatives as potential chiral selectors, sulfobutyl-ether-α-CD (SBE-α-CD) was selected for the enantioseparation. For the optimization, a factorial analysis study was performed by orthogonal experimental design. Six experimental factors were chosen as variable parameters: temperature, applied voltage, chiral selector and BGE concentrations, pH, and the parameters of the hydrodynamic injection. The optimized system still was not considered final as the second peak (S-enantiomer) migrated too close to the EOF, resulting in a potential inaccuracy during the determination of the chiral impurity. To fine-tune the method "one factor at a time" variation approach was applied. The final method (applying 15°C capillary temperature, 40 mbar × 4 s hydrodynamic injection, 25 kV voltage in 75 mM acetate-Tris buffer [pH 4.75] containing 20 mM SBE-α-CD as chiral selector) was validated according to the ICH guideline. RSD percentage of the resolution value, migration times, and corrected peak areas were below 5% during testing repeatability and intermediate precision. LOD and LOQ values were found to be 2.5 and 7.5 μg/mL, respectively. The method is considered linear in the 7.5-180 μg/mL range for the R-enantiomer. The robustness of the method was justified using Plackett-Burmann statistical experimental design., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bisimidazolium salts with one central biphenyl binding site and two terminal adamantyl binding sites form water-soluble binary or ternary aggregates with cucurbit[7]uril (CB7) and β-cyclodextrin (β-CD) with rotaxane and pseudorotaxane architectures. The observed arrangements result from cooperation of the supramolecular stopper binding strength and steric barriers against free slippage of the CB7 and β-CD host molecules over the bisimidazolium guest axle., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bongkrekic acid (BKA), isolated from the bacterium Burkholderia cocovenenans, is an inhibitor of adenine nucleotide translocator, which inhibits apoptosis, and is thus an important tool for the mechanistic investigation of apoptosis. An efficient total synthesis of BKA has been achieved by employing a three-component convergent strategy based on Kocienski-Julia olefination and Suzuki-Miyaura coupling. It is noteworthy that segment B has been prepared as a new doubly functionalized coupling partner, which contributes to shortening of the number of steps. Torquoselective olefination with an ynolate has also been applied for the efficient construction of an unsaturated ester. Furthermore, it is revealed that 1-methyl-2-azaadamantane N-oxyl is an excellent reagent for final oxidation to afford BKA in high yield. Based on the total synthesis, several BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the apoptosis inhibitory activity of BKA. More easily available BKA analogues with potent apoptosis inhibitory activity were also developed., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

(1-Adamantyl)methyl glycidyl ether (AdaGE) is introduced as a versatile monomer for oxyanionic polymerization, enabling controlled incorporation of adamantyl moieties in aliphatic polyethers. Via copolymerization with ethoxyethyl glycidyl ether (EEGE) and subsequent cleavage of the acetal protection groups of EEGE, hydrophilic linear polyglycerols with an adjustable amount of pendant adamantyl moieties are obtained. The adamantyl unit permits control over thermal properties and solubility profile of these polymers (LCST). Additionally, AdaGE is utilized as a termination agent in carbanionic polymerization, affording adamantyl-terminated polymers. Using these structures as macroinitiators for the polymerization of ethylene oxide affords amphiphilic, in-chain adamantyl-functionalized block copolymers., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Supramolecular hydrogels formed by a host-guest interaction show self-healing properties. The cube-shaped hydrogels with β-cyclodextrin and adamantane guest molecules mend after being broken. The hydrogels sufficiently heal to form a single gel, and the initial strength is restored. Although contact between a freshly cut and uncut surface does not mend the gels, two freshly cut surfaces selectively mend., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We have developed a straightforward strategy to multimerize an apoptogenic peptide that mimics the natural tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by using adamantane-based dendrons as multivalent scaffolds. The selective binding affinity of the ligands to TRAIL receptor 2 (TR2) was studied by surface plasmon resonance, thus demonstrating that the trimeric and hexameric forms of the peptide exert an increased affinity of about 1500- and 20,000-fold, respectively, relative to the monomer. Moreover, only the trimeric and hexameric ligands were able to induce cell death in TR2 expressing cells (BJAB), thus confirming that a multivalent form of the peptide is necessary to trigger a substantial TR2-dependent apoptotic response in vitro. These results provide interesting insight into the multivalency effect on biological ligand/receptor interactions for future therapeutic applications., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new class of inorganic-organic hybrid porous materials has been synthesized by a reaction between octa(hydridosilsesquioxane) (H(8)Si(8)O(12)), which has a double-four-ring (D4R) structure, and various diols, such as 1,3-propanediol (PD), 1,4-cyclohexanediol (CHD), and 1,3-adamantanediol (AD). Solid-state (29) Si magic-angle-spinning NMR spectroscopic analysis confirmed that most of the corner Si-H groups reacted with diols to form Si-O-C bonds with retention of the D4R cage. Nitrogen adsorption-desorption studies showed that the products are microporous solids with high BET surface areas (up to ≈580 m(2) g(-1) for CHD- and AD-linked products). If n-alkanediols are used as linkers, the surface area becomes smaller as the number of carbon atoms is increased. The thermal and hydrolytic stability of the products strongly depend on the type of diol linkers. The highest stabilities are found for the AD-linked products, which are thermally stable up to around 400 °C and remain intact even after being soaked in water for 1 day. In contrast, the PD-linked product is easily hydrolyzed in water to give microporous silica. These results offer a new route toward a series of silica-based porous materials with unique structures and properties., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A supramolecular assembly scheme is developed to enable the facile in-situ immobilization of enzymes in a microfluidic channel system. A combination of orthogonal supramolecular interactions of host (β-cyclodextrin)-guest (adamantane) and biotin-Streptavidin (SAv) interactions are employed to generate reusable homogeneous enzyme layers in microchannels. The structural integrity and catalytic activity of the immobilized enzyme calf-intestine alkaline phosphatase (AlkPh) is demonstrated. From the kinetic analysis of a dephosphorylation reaction, the specificity constant k(cat)/K(M) for immobilized alkaline phosphatase in the channels is on the order of 10(5) M(-1) s(-1) and comparable to known literature values in other environments. These observations are ascribed to the good access of the substrate to favorably oriented enzymes across the microchannel. Therefore, this study demonstrates the great potential for adopting a supramolecular assembly scheme to immobilize enzymes in microfluidic devices., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Show some metal: the first bimetallic adamantane-like cluster, [{Fe(CO)(3)}(4){SnI}(6)I(4)](2-), was prepared by an ionic-liquid-based synthesis. The valence states of iron and tin were verified based on bond-length considerations, FT-IR and (119)Sn Mössbauer spectroscopy, as well as with DFT calculations., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The thermodynamically controlled reactions of water-soluble tetraformylcavitand 2 with two equivalents of H(2)N(CH(2))(n) NH(2) (n=2-4) in the presence of a suitable templating guest give hemicarceplexes 1 a-c⋅guest, the yield of which depends on the match between size and shape of the guest and that of the inner phase. These hemicarceplexes are dynamic and dissociate upon addition of acid and reform upon basification. In water, they exchange guests through temporary hydrolysis of imine bonds. To test 1 b as molecular reaction flask, 3-noradamantyldiazirine 6 was encapsulated and photolyzed at 350 nm to produce Bredt olefin protoadamantene 5 and 1-noradamantyldiazomethane 8 in a 4:1 ratio. Encapsulated protoadamantene is stable for days at room temperature in (CD(3))(2)SO/CD(3)CN (t(1/2) = 5.5 days) and has a lifetime of several minutes in D(2)O., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A polyhedral oligomeric silsesquioxane (POSS)-based supramolecular amphiphile is prepared from the host-guest inclusion complexation between a mono adamantane-functionalized POSS (AD-POSS) and a β-cyclodextrin oligomer (P(β-CD)). Assisted by the interface of H(2)O/toluene, the obtained supramolecular hybrids self-assemble into stable hollow nanospheres with thick walls. These hollow nanospheres aggregate together into a sphere layer through a spin coating technique, which then further transforms into a thin porous film containing nanometer-scale holes. The hollow nanospheres have a low cytotoxicity. The in vitro cell culture indicates the nanoporous films promote adhesion and proliferation of cells. The self-assembly morphologies and structures have been carefully characterized by SEM, TEM, AFM, DLS, XPS and water-contact angle measurements, and the self-assembly mechanism has also been discussed., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Be my guest: A supramolecular host-guest interaction is utilized for highly efficient bioorthogonal labeling of cellular targets. Antibodies labeled with a cyclodextrin host molecule bind to adamantane-labeled magnetofluorescent nanoparticles (see picture) and provide an amplifiable strategy for biomarker detection that can be adapted to different diagnostic techniques such as molecular profiling or magnetic cell sorting., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The temperature-dependent dynamic properties of [Cu(II)(2)(ADCOO)(4)(DMF)(2)]⋅(DMF)(2) (1) and [Cu(II)(2)(ADCOO)(4)(AcOEt)(2)] (2) crystals were examined by X-ray crystallography, (1)H NMR spectroscopy, and measurements of the dielectric constants and magnetic susceptibilities (ADCOO = adamantane carboxylate, DMF = N,N-dimethylformamide, and AcOEt = ethyl acetate). In both crystals, four ADCOO groups bridged a binuclear Cu(II)-Cu(II) bond, forming a paddle-wheel [Cu(II)(2)(ADCOO)(4)] structure. The oxygen atoms of two DMF molecules in crystal 1 and two AcOEt molecules in crystal 2 were coordinated at axial positions of the [Cu(II)(2)(ADCOO)(4)] moiety, forming [Cu(II)(2)(ADCOO)(4)(DMF)(2)] and [Cu(II)(2)(ADCOO)(4)(AcOEt)(2)], respectively. Two additional DMF molecules were included in the unit cell of crystal 1, whereas AcOEt was not included in the unit cell of crystal 2. The structural analyses of crystal 1 at 300 K showed three-fold rotation of the adamantyl groups, whereas rotation of the adamantyl groups of crystal 2 at 300 K was not observed. Thermogravimetric measurements of crystal 1 indicated a gradual elimination of DMF upon increasing the temperature above 300 K. The dynamic behavior of the crystallized DMF yielded significant temperature-dependent dielectric responses in crystal 1, which showed a huge dielectric peak at 358 K in the heating process. In contrast, only small frequency-dependent dielectric responses were observed in crystal 2 because of the freezing of the molecular rotation of the adamantyl groups. The magnetic behavior was dominated by the strong antiferromagnetic coupling between the two S = 1/2 spins of the Cu(II)-Cu(II) site, with magnetic exchange energies (J) of -265 K (crystal 1) and -277 K (crystal 2)., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new strategy for affinity-based drug delivery by modification of the drug rather than modification of the device is presented. Rifampin is modified to contain either one or two PEG-adamantane arms, and the drug release properties of dimeric coumermycin are compared to novobiocin with only one biding domain. The drugs are loaded into affinity-based and diffusion-only delivery platforms, the loading efficiency is calculated, and the release kinetics is determined in vitro. The presence of additional binding domains prolongs the release of antibiotics. Release rates differ little between modified and unmodified drug from the diffusion-only system. The results demonstrate the feasibility of custom-tuning drug delivery by multiplexing interactions with an affinity-based polymer platform.

Nanoassemblies formed by host/guest interactions between two polymers in aqueous media are studied. Two types of polymers with the same dextran backbone are modified with adamantyl or βCD groups. The sizes of the spontaneously formed nanoassemblies depend on the βCD:Ada ratio and on the total concentration and composition of the mixtures. The results can be rationalized by assuming a core/shell structure of the nanoassemblies, the core resulting from associative phase separation of the two polymers and being stabilized by an external shell made of Ada-grafted dextran and containing ions adsorbed from the solution. Hydrophobic compounds such as benzophenone can be incorporated efficiently without inducing changes in properties of the nanoassemblies., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Elevated levels of active glucocorticoids have been implicated in the development of several phenotypes of metabolic syndrome, such as type 2 diabetes and obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the intracellular conversion of inactive cortisone to cortisol. Selective 11β-HSD1 inhibitors have shown beneficial effects in various conditions, including diabetes, dyslipidemia and obesity. A series of adamantyl ethanone pyridyl derivatives has been identified, providing potent and selective inhibitors of human 11β-HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β-HSD1 and are selective for this isoform, with no activity against 11β-HSD2 and 17β-HSD1. Structure-activity relationship studies reveal that an unsubstituted pyridine tethered to an adamantyl ethanone motif through an ether or sulfoxide linker provides a suitable pharmacophore for activity. The most potent inhibitors have IC₅₀ values around 34-48 nM against human 11β-HSD1, display reasonable metabolic stability in human liver microsomes, and weak inhibition of key human CYP450 enzymes., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

DNA governs the storage and transfer of genetic information through generations in all living systems with the exception of some viruses. Its physicochemical nature and the Watson-Crick base pairing properties allow molecular constructions at nanometer length, thereby enabling the design of desired structural motifs, which can self-assemble to form large supramolecular arrays and scaffolds. The tailor-made DNAs have been an interesting material for such designed nanoscale constructions. However, the synthesis of specific structures with a desired molecular function is still in its infancy and therefore has to be further explored. To add a new dimension to this approach, we have synthesized a rigid three-way branched adamantane motif, which is capable of forming highly stable DNA networks. The moiety generated could serve as a useful building block for DNA-based nanoconstructions., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Poly(N-isopropylacrylamide) (PNIPAM) oligomer containing one adamantyl (AD) and two β-cyclodextrin (β-CD) moieties at the chain terminals, AD-PNIPAM-(β-CD)(2), was synthesized by atom transfer radical polymerization (ATRP) and successive click reactions. In aqueous solution, AD-PNIPAM-(β-CD)(2) spontaneously forms supramolecular thermoresponsive hyperbranched polymers via molecular recognition between AD and β-CD moieties. To the best of our knowledge, this work represents the first report of the construction of supramolecular thermoresponsive hyperbranched polymers from well-defined polymeric AB(2) building units., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The cyclic cationic antimicrobial peptide gramicidin S (GS) is an effective topical antibacterial agent that is toxic for human red blood cells (hemolysis). Herein, we present a series of amphiphilic derivatives of GS with either two or four positive charges and characteristics ranging between very polar and very hydrophobic. Screening of this series of peptide derivatives identified a compound that combines effective antibacterial activity with virtually no toxicity within the same concentration range. This peptide acts against both Gram-negative and Gram-positive bacteria, including several MRSA strains, and represents an interesting lead for the development of a broadly applicable antibiotic.

This article systematically investigates the influence of the properties of inhomogeneous N-auxiliary ligands and pH value on the helical structures of complexes based on C(2)-symmetric ligand 1,3-adamantanedicarboxylic acid (H(2)ADC). Five kinds of neutral ligands (phen=1,10-phenanthroline, bipy=4,4'-bipyridine, bpa=1,2-bis(4-pyridyl)ethane, bpe=1,2-bis(4-pyridyl)ethane, and bpp=1,3-bis(4-pyridyl)propane) were selected, and a series of new Zn(II)/Co(II) dicarboxylates have been synthesized by slow diffusion, namely, [Zn(phen)(ADC)(H(2)O)](2).CH(3)OH (1), {[Zn(ADC)(bpe)].H(2)O}(n) (2), {[Zn(ADC)(bipy)].2H(2)O}(n) (3), {[Zn(ADC)(bpa)](2).5H(2)O}(n) (4), {[Zn(ADC)(bpp)](2).CH(3)OH}(n) (5), {[Zn(ADC)(bpp)]}(n) (6), {[Co(ADC)(bpp)(CH(3)OH)(H(2)O)].CH(3)OH2 H(2)O}(n) (7), and {[Co(ADC)(bpp)]}(n) (8). Single-crystal X-ray structural analysis shows that complex 1 forms a 0D dinuclear with closed-loop unit. The complex 2 is a 2D layer framework. Compounds 3 and 4 are isomorphous with a small discrepancy and present one-dimensional chainlike structures. It is interesting that the 2D organic-inorganic hybrid frameworks containing meso-helical chains have been observed. Compound 5 is a 2D interpenetrated network with (4,4) topology, in which homochiral left-handed helical chains are arranged in an ABAB sequence parallel to the plane defined by (a,c), and right-handed helical chains running along the a axis are also observed in the solid state, resulting in a meso-helical structure. Compounds 6, 7, and 8 crystallize in a chiral space group P212121. Highly dimensional 6 and 8 are essentially isostructural and present a threefold interpenetrated 3D diamondoid network containing three helical chains, whereas 7 exhibits a 2D grid layer with a left-handed helical chain. Furthermore, thermal stability, X-ray powder diffraction, and the luminescent properties of 1-6 are also discussed.

11Beta-hydroxysteroid dehydrogenases (11beta-HSDs) are key enzymes regulating the pre-receptor metabolism of glucocorticoid hormones. The modulation of 11beta-HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue-specific glucocorticoid action by regulating 11beta-HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11beta-HSD1. The most active compounds identified (52, 62, 72, 92, 103 and 104) display potent inhibition of 11beta-HSD1 with IC(50) values in the 50-70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X-ray crystal structures of human 11beta-HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor.

Bacteria have developed resistance to almost all existing antibiotics known today and this has been a major issue over the last few decades. The search for a new class of antibiotics with a new mode of action to fight these multiply-drug-resistant strains, or "superbugs", allowed a team of scientists at Merck to discover two novel antibiotics, platensimycin and platencin using advanced screening strategies, as inhibitors of bacterial fatty acid biosynthesis, which is essential for the survival of bacteria. Though both these antibiotics are structurally related, they work by slightly different mechanisms and target different enzymes conserved in the bacterial fatty acid biosynthesis. This Focus Review summarizes the synthetic and biological aspects of these natural products and their analogues and congeners.

An artificial glycocalix self-assembles when unilamellar bilayer vesicles of amphiphilic beta-cyclodextrins are decorated with maltose and lactose by host-guest interactions. To this end, maltose and lactose were conjugated with adamantane through a tetra(ethyleneglycol) spacer. Both carbohydrate-adamantane conjugates strongly bind to beta-cyclodextrin (K(a) approximately 4 x 10(4) M(-1)). The maltose-decorated vesicles readily agglutinate (aggregate) in the presence of the lectin concanavalin A, whereas the lactose-decorated vesicles agglutinate in the presence of peanut agglutinin. The orthogonal multivalent interaction in the ternary system of host vesicles, guest carbohydrates, and lectins was investigated by using isothermal titration calorimetry, dynamic light scattering, UV/Vis spectroscopy, and cryogenic transmission electron microscopy. It was shown that agglutination is reversible, and the noncovalent interaction can be suppressed and eliminated by the addition of competitive inhibitors, such as D-glucose or beta-cyclodextrin. Also, it was shown that agglutination depends on the surface coverage of carbohydrates on the vesicles.

Gold(I) complexes bearing water-soluble phosphine ligands, including 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA), and sodium triphenylphosphine trisulfonate (TPPTS), in combination with thionate ligands, were screened for their antiproliferative activities against human ovarian cancer cell lines A2780 either sensitive or resistant to cisplatin. In addition, the compounds were screened for their inhibition of mammalian thioredoxin reductases (TrxR), enzymes that are overexpressed in many tumor cells and contribute to drug resistance. The gold(I)-phosphine complexes efficiently inhibited cytosolic and mitochondrial TrxRs at concentrations that did not affect the related oxidoreductase glutathione reductase (GR). Additional complementary information on the enzyme metallation process and potential gold binding sites was obtained through the application of a specific biochemical assay using a thiol-tagging reagent, BIAM (biotin-conjugated iodoacetamide).

The recent discovery of the natural product platensimycin as a new antibiotic lead structure has triggered the synthesis of numerous organic derivatives for structure-activity relationship studies. Herein, we describe the synthesis, characterization and biological evaluation of the first organometallic antibiotic inspired by platensimycin. Two bioorganometallic compounds containing (eta(6)-pentamethylbenzene)Cr(CO)(3) (2) and (eta(6)-benzene)Cr(CO)(3) (3), linked by an amide bond to the aromatic part of platensimycin, were synthesized. Their antibiotic activities were tested against B. subtilis 168 (Gram positive) and E. coli W3110 (Gram negative) bacterial strains. Both compounds were found to be inactive against E. coli but derivative 2 inhibits B. subtilis growth at a moderate MIC value of 0.15 mM. To test the intrinsic toxicity of chromium, several chromium salts along with {eta(6)-(3-pentamethylphenyl propionic acid)}Cr(CO)(3) (5) and {eta(6)-(3-phenyl propionic acid)}Cr(CO)(3) (6) were tested against both bacterial strains. No activity was observed against E. coli for any of the compounds; B. subtilis growth was not inhibited by Cr(NO(3))(3) and only very weakly by 5, K(2)Cr(2)O(7) and Na(2)CrO(4) at MIC values of 0.5, 0.68 and 1.24 mM, respectively. Compounds 2, 3, 5 and 4 (the pure organic analogue of 2) show similar cytotoxicity against HeLa, HepG2 and HT-29 mammalian cell lines. Furthermore, the cellular uptake and the intracellular distribution of compounds 2, 3 and Cr(NO(3))(3) in B. subtilis were studied using atomic absorption spectroscopy to gain insight in to the possible cellular targets. Compound 2 was found to be readily taken up and distributed almost equally among cytosol, cell debris and cell membrane in B. subtilis.