High-intensity ultrasound and microwave, alone or combined, promote Pd/C-catalyzed aryl-aryl couplings

Pd-catalyzed homo- and cross-couplings of boronic acids and aryl halides were successfully carried out both in aqueous media under high-intensity ultrasound (US) and in DME under microwave (MW). Heterogeneous catalysis with Pd/C was employed, avoiding phosphine ligands and phase-transfer catalysts. In a trial series involving 15 different iodo- and bromoaryls and 7 boronic acids, both energy sources drastically reduced reaction times affording biaryls in acceptable to good yields. With palladium(II) acetate as catalyst, electron-deficient aryl chlorides also reacted, affording a few biaryls in acceptable yields. Ullmann-type zinc-mediated homocoupling of iodo- and bromoaryls in the presence of Pd/C under CO₂ atmosphere was achieved in aqueous media under US, though not under MW. Suzuki homo- and cross-couplings were also carried out in a new reactor developed in our laboratory, featuring combined US and MW irradiation, further improving a green synthetic method.     

Fluorine-NMR competition binding experiments for high-throughput screening of large compound mixtures

High-throughput ligand-based NMR screening with competition binding experiments is extended to (19)F detection. Fluorine is a favorable nucleus for these experiments because of the significant contribution of the Chemical Shift Anisotropy (CSA) to the (19)F transverse relaxation of the ligand signal when bound to a macromolecular target. A low to moderate affinity ligand containing a fluorine atom is used as a reference molecule for the detection and characterization of new ligands. Titration NMR experiments with the selected reference compound are performed for finding the optimal set-up conditions for HTS and for deriving the binding constants of the identified NMR hits. Rapid HTS of large chemical mixtures and plant or fungi extracts against the receptor of interest is possible due to the high sensitivity of the (19)F nucleus and the absence of overlap with the signals of the mixtures to be screened. Finally, a novel approach for HTS using a reference molecule in combination with a control molecule is presented.     

Bis(oxofluorenediyl)oxacyclophanes: synthesis, crystal structure and complexation with paraquat in the gas phase

The first three representatives of the new family of oxacyclophanes incorporating two 2,7-dioxyfluorenone fragments, connected by [-CH(2)CH(2)O-](m) spacers (m=2-4), have been synthesized. The yield of the smallest oxacyclophane (m=2) is considerably higher with respect to the larger ones (m=3 and m=4), which are formed in comparable yields. Molecular modeling and NMR spectra analysis of the model compounds suggest that an essential difference in oxacyclophanes yields is caused by formation of quasi-cyclic intermediates, which are preorganized for macrocyclization owing to intramolecular pi-pi stacking interactions between the fluorenone units. The solid-state structures of these oxacyclophanes exhibit intra- and intermolecular pi-pi stacking interactions that dictate their rectangular shape in the fluorenone backbone and crystal packing of the molecules with the parallel or T-shape arrangement. The crystal packing in all cases is also sustained by weak C--HO hydrogen bonds. FAB mass spectral analysis of mixtures of the larger oxacyclophanes (m=3 and m=4) and a paraquat moiety revealed peaks corresponding to the loss of one and two PF(6) (-) counterions from the 1:1 complexes formed. However, no signals were observed for complexes of the paraquat moiety with the smaller oxacyclophane (m=2). Computer molecular modeling of complexes revealed a pseudorotaxane-like incorporation of the paraquat unit, sandwiched within a macrocyclic cavity between the almost parallel-aligned fluorenone rings of the larger oxacyclophanes (m=3 and m=4). In contrast to this, only external complexes of the smallest oxacyclophane (m=2) with a paraquat unit have been found in the energy window of 10 kcal mol(-1).     

Sensitivity improvement in 19F NMR-based screening experiments: theoretical considerations and experimental applications

NMR-based binding and functional screening performed with FAXS (fluorine chemical shift anisotropy and exchange for screening) and 3-FABS (three fluorine atoms for biochemical screening) represents a potential alternative approach to high-throughput screening for the identification of novel potential drug candidates. The major limitation of this method in its current status is its intrinsic low sensitivity that limits the number of tested compounds. One approach for overcoming this problem is the use of a cryogenically cooled (19)F probe that reduces the thermal noise in the receiver circuitry. Sensitivity improvement in the two screening techniques achieved with the novel cryogenic (19)F probe technology permits an increased throughput, detection of weaker binders and inhibitors (relevant in a fragment-based lead discovery program), detection of slow binders, and reduction in protein and substrate consumption. These aspects are analyzed with theoretical simulations and experimental quantitative performance evaluation. Application of 3-FABS combined with the cryogenic (19)F probe technology to rapid screening at very low enzyme concentrations and the current detection limits reached with this approach are also presented.     

Challenges and prospects of ambient hybrid solar cell applications

The impending implementation of billions of Internet of Things and wireless sensor network devices has the potential to be the next digital revolution, if energy consumption and sustainability constraints can be overcome. Ambient photovoltaics provide vast universal energy that can be used to realise near-perpetual intelligent IoT devices which can directly transform diffused light energy into computational inferences based on artificial neural networks and machine learning. At the same time, a new architecture and energy model needs to be developed for IoT devices to optimize their ability to sense, interact, and anticipate. We address the state-of-the-art materials for indoor photovoltaics, with a particular focus on dye-sensitized solar cells, and their effect on the architecture of next generation IoT devices and sensor networks.

The impending implementation of billions of Internet of Things and wireless sensor network devices has the potential to be the next digital revolution, if energy consumption and sustainability constraints can be overcome.     

Hierarchy of hydrogen bonding in bis­(1,4,7‐trioxa‐10‐azoniacyclo­dodecane) bis­(4‐amino­benzoate) trihydrate

In the title compound, 2C₈H₁₈NO₃⁺·2C₇H₆NO₂⁻·3H₂O, proton transfer occurs from the carboxylic acid group of the 4‐amino­benzoic acid (PABA) mol­ecule to the amine group of the macrocycle, resulting in the formation of a salt‐like adduct. The anions are combined into helical chains which are further bound by the water mol­ecules into sheets. The macrocyclic cations are situated between these layers and are bound to the anions both directly and via bridging water mol­ecules. The structure exhibits a diverse system of hydrogen bonding.     

Theory of long-lived nuclear spin states in solution nuclear magnetic resonance. I. Singlet states in low magnetic field

We have recently demonstrated the existence of exceptionally long-lived nuclear spin states in solution-state nuclear magnetic resonance. The lifetime of nuclear spin singlet states in systems containing coupled pairs of spins-12 may exceed the conventional relaxation time constant T1 by more than an order of magnitude. These long lifetimes may be observed if the long-lived singlet states are prevented from mixing with rapidly relaxing triplet states. In this paper we provide the detailed theory of an experiment which uses magnetic field cycling to observe slow singlet relaxation. An approximate expression is given for the magnetic field dependence of the singlet relaxation rate constant, using a model of intramolecular dipole-dipole couplings and fluctuating external random fields.     

Novel selenium-containing non-natural diamino acids

The general synthesis of a new class of non-natural diamino acids, 2-amino-3-[(2′-aminoalkyl)seleno]propanoic acids, or Se-(aminoalkyl)selenocysteines, is reported. Under the conditions devised, enantiopure N-Boc-protected β-l-iodoamines, which are readily generated from proteinogenic α-amino acids, were treated with the selenolate anion obtained from NaBH₄ splitting of the Se-Se bond in commercial l-selenocystine. The Se-alkylation products were enantiomerically pure and the reaction is high yielding (92-98%), without any detectable traces of accompanying by-products.     

Combined use of liquid chromatography-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry for the characterization of an acarbose degradation product

Directly coupled LC-MS and LC-NMR were applied to identify and structurally characterize an acarbose degradation product A in acidic media. A comparative analysis of the stop-flow LC-NMR (1H and TOCSY) and LC-MS data provided evidence that A is structurally related to acarbose, differing from the parent compound in a number of subunits present in the molecule. Spectral analysis revealed that A was the alpha-glucosidase inhibitor amylostatin XG. Complementary information obtained from the two methods led to the structural elucidation of A which was later corroborated by high-resolution NMR spectroscopy of the isolated molecule.