Transition-metal-complexed cyclic [3]- and [4]pseudorotaxanes containing rigid ring-and-filament conjugates: synthesis and solution studies

By using the "gathering-and-threading" effect of copper(I) with rigid ring-and-string conjugates, daisy-chain-type [3]- and [4]pseudorotaxanes could be prepared in high yields. The organic fragment used consisted of a 2,9-diphenyl-1,10-phenanthroline (dpp)-containing ring attached to a coordinating filament capable of threading through the ring of another molecule by coordination to copper(I). The bidentate chelate introduced in the axis was also a 1,10-phenanthroline (phen) derivative with two methyl groups ortho to the nitrogen atoms of the phen unit. The organic component was prepared following a multistep strategy, one of the key steps being the attachment of the ring to the lateral axis. This connection was done by a condensation reaction between an ortho dione located at the back of a ring-incorporated phen and an aromatic aldehyde, which was the end-function of the thread. An oxazole nucleus was obtained after the condensation, which provided a rigid connection between the ring and the axis. In this way, the coordination axes of the ring-incorporated bidentate chelate and of the ligand belonging to the lateral filament were approximately orthogonal to one another. The design was such that the tetrameric complex, a [4]pseudorotaxane, seemed to be the most stable species, owing to the mutual geometrical arrangement of the filament and the ring. Various spectroscopic techniques, such as (1)H NMR spectroscopy, including DOSY, and electrospray ionization mass spectroscopy (ESI-MS), clearly demonstrated that a mixture of cyclic [3]- and [4]pseudorotaxane was obtained; the proportions of both components depended on concentration and temperature. Copper(I) was not the only metal center leading to the formation of cyclic pseudorotaxanes. A similar effect was observed with silver(I) as the templating metal: quantitative formation of threaded species was observed, with a higher proportion of trimer over tetramer than in the copper(I) case. Concentration and temperature effects were investigated for both series of Cu(I) - and Ag(I) -complexed threaded species showing that formation of the trimer was favored upon dilution or heating of the solution.     

Visualizing zeptomole (electro)catalysis at single nanoparticles within an ensemble

The relationship between the structural properties, such as the size and the shape, of a catalytic nanoparticle and its reactivity is a key concept in (electro)catalysis. Current understanding of this relationship is mainly derived from studies involving large ensembles of nanoparticles (NPs). However, the results necessarily reflect the average catalytic behavior of an ensemble, even though the properties of individual particles may vary widely. Here, we demonstrate a novel approach using scanning electrochemical cell microscopy (SECCM) to locate and map the reactivity of individual NPs within an electrocatalytic ensemble, consisting of platinum NPs supported on a single carbon nanotube. Significantly, our studies show that subtle variations in the morphology of NPs lead to dramatic changes in (potential-dependent) reactivity, which has important implications for the design and assessment of NP catalysts. The instrumental approach described is general and opens up new avenues of research in functional imaging, nanoscale electron transfer, and catalysis.     

In search of a new class of stable nitroxide: synthesis and reactivity of a peri-substituted N,N-bissulfonylhydroxylamine

Acyclic bissulfonylnitroxides have never been isolated, and degrade through fragmentation. In an approach to stabilising a bissulfonylnitroxide radical, the cyclic, peri-substituted N,N-bissulfonylhydroxylamine, 2-hydroxynaphtho[1,8-de][1,3,2]dithiazine 1,1,3,3-tetraoxide (1), has been prepared by formal nitrogen insertion into the sulfur-sulfur bond of a sulfinylsulfone, naphtho[1,8-cd][1,2]dithiole 1,1,2-trioxide. The heterocyclic ring of 1 is shown to adopt a sofa conformation by X-ray crystallography, with a pseudo-axial hydroxyl group. N,N-Bissulfonylhydroxylamine 1 displays high thermal, photochemical and hydrolytic stability compared to acyclic systems. EPR analysis reveals formation of the corresponding bissulfonylnitroxide 2 upon oxidation of 1 with the Ce(IV) salts CAN and CTAN. Although 2 does not undergo fragmentation, it cannot be isolated, since hydrogen atom abstraction to reform 1 occurs in situ. The stability and reactivity of 1 and 2 are compared with the known cyclic benzo-fused N,N-bissulfonylhydroxylamine, N-hydroxy-O-benzenedisulfonimide (6), for which the X-ray data, and EPR of the corresponding nitroxide 10, are also reported for the first time.     

Internal Lewis acid assisted hydrogen bond donor catalysis

Boronate ureas are introduced as a new class of noncovalent catalysts for conjugate addition reactions with enhanced activity. Through intramolecular coordination of the urea functionality to a strategically placed Lewis acid, rate enhancements up to 10 times that of more conventional urea catalysts are observed. The tunable nature of boronate ureas is a particularly attractive feature and enables the rational design of catalysts for optimal performance, in terms of both activity and stereocontrol, in new bond-forming processes.     

Microbial metabolism. Part 12. Isolation, characterization and bioactivity evaluation of eighteen microbial metabolites of 4'-hydroxyflavanone

Fermentation of 4'-hydroxyflavanone (1) with fungal cultures, Beauveria bassiana (ATCC 13144 and ATCC 7159) yielded 6,3',4'-trihydroxyflavanone (2), 3',4'-dihydroxyflavanone 6-O-β-D-4-methoxyglucopyranoside (3), 4'-hydroxyflavanone 3'-sulfate (4), 6,4'-dihydroxyflavanone 3'-sulfate (5) and 4'-hydroxyflavanone 6-O-β-D-4-methoxyglucopyranoside (7). B. bassiana (ATCC 13144) and B. bassiana (ATCC 7159) in addition, gave one more metabolite each, namely, flavanone 4'-O-β-D-4-methoxyglucopyranoside (6) and 6,4'-dihydroxyflavanone (8) respectively. Cunninghamella echinulata (ATCC 9244) transformed 1 to 6,4'-dihydroxyflavanone (8), flavanone-4'-O-β-D-glucopyranoside (9), 3'-hydroxyflavanone 4'-sulfate (10), 3',4'-dihydroxyflavanone (11) and 4'-hydroxyflavanone-3'-O-β-D-glucopyranoside (12). Mucor ramannianus (ATCC 9628) metabolized 1 to 2,4-trans-4'-hydroxyflavan-4-ol (13), 2,4-cis-4'-hydroxyflavan-4-ol (14), 2,4-trans-3',4'-dihydroxyflavan-4-ol (15), 2,4-cis-3',4'-dihydroxyflavan-4-ol (16), 2,4-trans-3'-hydroxy-4'-methoxyflavan-4-ol (17), flavanone 4'-O-α-D-6-deoxyallopyranoside (18) and 2,4-cis-4-hydroxyflavanone 4'-O-α-D-6-deoxyallopyranoside (19). Metabolites 13 and 14 were also produced by Ramichloridium anceps (ATCC 15672). The former was also produced by C. echinulata. Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antiprotozoal activities against selected organisms.     

TIRF microscopy as a screening method for non-specific binding on surfaces

We report a method for studying nanoparticle-biosensor surface interactions based on total internal reflection fluorescence (TIRF) microscopy. We demonstrate that this simple technique allows for high throughput screening of non-specific adsorption (NSA) of nanoparticles on surfaces of different chemical composition. Binding events between fluorescent nanoparticles and functionalized Zeonor? surfaces are observed in real-time, giving a measure of the attractive or repulsive properties of the surface and the kinetics of the interaction. Three types of coatings have been studied: one containing a polymerized aminosilane network with terminal -NH(2) groups, a second film with a high density of -COOH surface groups and the third with sterically restraining branched poly(ethylene)glycol (PEG) functionality. TIRF microscopy revealed that the NSA of nanoparticles with negative surface charge on such modified coatings decreased in the following order -NH(2)>-branched PEG>-COOH. The surface specificity of the technique also allows discrimination of the degree of NSA of the same surface at different pH.     

A sulfone-based strategy for the preparation of 2,4-disubstituted furan derivatives

2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1-propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming step involves a deacetylation, and the selectivity of this process depends upon the steric demand of the R group. The substituent in position 4 is elaborated by reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes. Oxidative or reductive desulfonylation produces the 2,4-disubstituted furans in 60-92% yield. This strategy has been used to prepare rabdoketone A (12) and the naturally occurring nematotoxic furoic acid 13.     

Synthesis and clathrates of oligomeric 2-O-naphthoide macrocycles

New macrocyclic O-naphthoides 4-6 were synthesized from dehydration reactions of 3-hydroxy- and 7-tert-butyl-3-hydroxy-2-naphthoic acids, respectively. Their X-ray structures were determined and their clathrate inclusion properties were investigated. Hexamer 6 formed an inclusion clathrate with four chloroform molecules. The trimer 5, by analogy with tri-o-thymotide, was studied for its potential optical resolution effects.     

Spectroscopic and theoretical study of the weakly bound H2-HCCCN dimer

Rotational spectra of the H(2)-HCCCN complex were studied using a pulsed-nozzle Fourier transform microwave spectrometer. Complexes containing the main and several minor isotopologues of cyanoacetylene (HCCC(15)N, DCCCN, and various (13)C containing isotopologues) and the two spin isomers of the H(2) molecule (paraH(2) and orthoH(2)) were investigated. Transitions of complexes with (14)N and D containing isotopologues have nuclear quadrupole hyperfine structures, which were measured and analyzed. Transitions of orthoH(2) molecule containing complexes show additional hyperfine structures due to nuclear magnetic proton spin-proton spin coupling of the hydrogen nuclei in the H(2) molecule. For orthoH(2)-HCCCN, both strong a- and weaker b-type transitions were measured and analyzed using a semirigid asymmetric rotor model. For the paraH(2)-HCCCN complex, only a-type transitions could be observed. The dimer complexes are floppy and have near T-shaped structures. Intermolecular interaction potential energy surfaces were calculated for H(2)-HCCCN using the coupled-cluster method with single and double excitations and noniterative inclusion of triple excitations [CCSD(T)]. Three orientations of the hydrogen molecule within the complex were considered. Equal weighting of the surfaces corresponding to the three hydrogen orientations provided an averaged potential energy surface. Bound-state rotational energy levels supported by the surfaces were determined for the different hydrogen orientations, as well as for the averaged surface. Simple scaling of the surfaces improved the agreement with the experimental results and produced surfaces with near spectroscopic accuracy.     

Biologically Relevant Metal-Cation Binding Induces Conformational Changes in Heparin Oligosaccharides as Measured by Ion Mobility Mass Spectrometry

Heparin interacts with many proteins and is involved in biological processes such as anticoagulation, angiogenesis, and antitumorigenic activities. These heparin-protein interactions can be influenced by the binding of various metal ions to these complexes. In particular, physiologically relevant metal cations influence heparin-protein conformations through electronic interactions inherent to this polyanion. In this study, we employed ion mobility mass spectrometry (IMMS) to observe conformational changes that occur in fully-sulfated heparin octasaccharides after the successive addition of metal ions. Our results indicate that binding of positive counter ions causes a decrease in collision cross section (CCS) measurements, thus promoting a more compact octasaccharide structure.