Supramolecular catalysis at work: diastereoselective synthesis of a molecular bowl with dynamic inner space

The supramolecular assistance to Pd(0)/Cu(I)-catalyzed cyclotrimerization of stannylated norbornene 7 has been investigated to give molecular bowl 1syn in a stereoselective fashion. Following a divergent strategy, racemic norbornene 7 was synthesized in satisfactory yield. Self-coupling, promoted by Pd(0)/Cu(I) catalysis acting in synergy with CsF, yielded molecular bowl 1syn in a moderate 30% yield. The reaction diastereoselectivity is affected by the concentration of Cu(I) and Cs+: increasing quantities of the cations enhanced the syn/anti ratio of the isolated cyclotrimer from statistical (1:3) to a more desirable (4.5:1) ratio, in favor of the molecular bowl 1syn. 1H NMR spectroscopic studies suggested the coordinating affinity of 1syn toward transition metals Cu(I), Ag(I), and Au(I), to account for the observed templation effect. In particular, the tridentate 1syn has been shown to bind to one Ag(I) cation in the assembly process that is driven with enthalpy (Delta H degrees = -19 +/- 2 kcal/mol, Delta S degrees = -45 eu). The complete coordination was not cooperative, and was hypothesized to be impeded with the adverse entropy. Accordingly, density functional theory (BP86) calculations of 1syn and its mono-, bis-, and tris-Ag(I) complexes suggested that the coordination of one to three silver cations is highly exothermic. The calculations also revealed that the bowl constriction is necessary for the aromatic arms to become preorganized and bind to a silver cation(s) (Delta E approximately 8 kcal/mol). Ultimately, Ag(I) has been shown to assist the diastereoselective formation of 1syn, lending support to the notion of template-directed synthesis.     

Observing molecular motions of a fluorinated ferroelectric liquid crystal using fluorine-19 NMR

Fluorine-19 NMR spectra have been recorded for both the phases (cholesteric and smectic C*) of the ferroelectric liquid crystal 2,3-difluoro-4-octyloxybiphenyl-4'(-4'-oxycarbonyl-(S)-1-chloro-3-methylbutyl)benzoate, using a conventional high-resolution NMR probe. The magnitude of the dipolar coupling constant, D_FF0, was found to increase with decreasing temperature in the cholesteric phase with a sudden increase (of approximately 1 000 Hz) at the cholesteric-smectic C* transition, whereafter a more gradual change was observed. The order parameter, was S_FF, subsequently calculated for each temperature.     

Observing the stereodynamics of chemical reactions using randomly oriented molecular beams

A new method is demonstrated to study the stereodynamics of simple chemical reactions that does not require the use of oriented (or aligned) molecular beams or measurements of the orientation state of product molecules. Instead, it is shown that by numerically combining accurate measurements of the state-to-state differential cross section for two or more rotational states of the reagent molecule, the separate contribution from the individual helicity states can be extracted. New molecular beam experiments are conducted for the D+H(2)-->HD+H reaction that confirm the validity of the method.     

Observing Single‐Molecule Dynamics at Millimolar Concentrations

Single‐molecule fluorescence microscopy is a powerful tool for revealing chemical dynamics and molecular association mechanisms, but has been limited to low concentrations of fluorescent species and is only suitable for studying high affinity reactions. Here, we combine nanophotonic zero‐mode waveguides (ZMWs) with fluorescence resonance energy transfer (FRET) to resolve single‐molecule association dynamics at up to millimolar concentrations of fluorescent species. This approach extends the resolution of molecular dynamics to >100‐fold higher concentrations, enabling observations at concentrations relevant to biological and chemical processes, and thus making single‐molecule techniques applicable to a tremendous range of previously inaccessible molecular targets. We deploy this approach to show that the binding of cGMP to pacemaking ion channels is weakened by a slower internal conformational change.     

Artificial molecular machines that can perform work

An artificial molecular machine consists of molecule or substituent components jointed together in a specific way so that their mutual displacements could be initiated using appropriate outside stimuli. Such an ability of performing mechanical motions by consuming external energy has endowed these tiny machines with vast fascinating potential applications in areas such as actuators, manipulating atoms/molecules, drug delivery, molecular electronic devices, etc. To date, although vast kinds of molecular machine archetypes have been synthesized in facile ways, they are inclined to be defined as switches but not true machines in most cases because no useful work has been done during a working cycle. More efforts need to be devoted on the utilization and amplification of the nanoscale mechanical motions among synthetic molecular machines to accomplish useful tasks. Here we highlight some of the recent advances relating to molecular machines that can perform work on different length scales, ranging from microscopic levels to macroscopic ones.     

Charge flipping at work: a case of pseudosymmetry

Charge flipping (CF) is an amazingly simple structure solution method that uses single-crystal X-ray diffraction data. It is truly ab initio, no preliminary information on atom types, chemical composition, or space group symmetry is required. The algorithm is iterative and alternates between real and reciprocal spaces. Its simplest version only changes (flips) the sign of the electron density below a threshold, while in reciprocal space, it prescribes the moduli of observed structure factors. In this communication, we apply the algorithm in practice. The selected example presents a whole range of difficulties: it is large, contains only light atoms, is noncentrosymmetric, and shows a particularly awkward pseudosymmetry. To solve it with any of the traditional methods requires many hours of computer time, followed by a day of expert's handwork to find missing and to remove spurious atoms. In contrast, the CF algorithm provides the complete structure in a few seconds and without human intervention. It is also remarkable that the success rate is 100%, that is, any starting point in the high-dimensional phase space leads to the solution. The treatment of translational pseudosymmetry is obviously a favorable case. Similar resistant structures with pseudosymmetries or ambiguous space groups are the practical applications where the CF method could well complement standard software procedures.     

Oscillatory molecular driving force for protein folding at high concentration: a molecular simulation

This paper presents a Langevin dynamics simulation that suggests a novel way to fold protein at high concentration, a fundamental issue in neurodegenerative diseases in vivo and the production of recombinant proteins in vitro. The simulation indicates that the folding of a coarse-grained beta-barrel protein at high concentration follows the "collapse-rearrangement" mechanism but it yields products of various forms, including single proteins in the native, misfolded, and uncollapsed forms and protein aggregates. Misfolded and uncollapased proteins are the "nucleus" of the aggregates that also encapsulate some correctly folded proteins (native proteins). An optimum hydrophobic interaction strength (epsilon*(p)) between the hydrophobic beads of the model protein, which results from a compromise between the kinetics of collapse and rearrangement, is identified for use in increasing the rate of folding over aggregating. Increased protein concentration hinders the structural transitions in both collapse and rearrangement and thus favors aggregation. A new method for protein folding at high concentration is proposed, which uses an oscillatory molecular driving force (epsilon*(p)) to promote the dissociation of aggregates in the low epsilon*(p) regime while promoting folding at a high epsilon*(p). The advantage of this method in enhancing protein folding while depressing aggregation is illustrated by a comparison with the methods based on direct dilution or applying a denaturant gradient.     

The efficiency of electrokinetic pumping at a condition of maximum work

Numerical methods are employed to examine the work, electric power input, and efficiency of electrokinetic pumps at a condition corresponding to maximum pump work. These analyses employ the full Poisson-Boltzmann equations and account for both convective and conductive electric currents, including surface conductance. We find that efficiencies at this condition of maximum work depend on three dimensionless parameters, the normalized zeta potential, normalized Debye layer thickness, and a fluid property termed the Levine number indicating the nominal ratio of convective to conductive electric currents. Efficiencies at maximum work exhibit a maximum for an optimum Debye layer thickness when the zeta potential and Levine number are fixed. This maximum efficiency increases with the square of the zeta potential when the zeta potential is small, but reaches a plateau as the zeta potential becomes large. The maximum efficiency in this latter regime is thus independent of the zeta potential and depends only on the Levine number. Simple analytical expressions describing this maximum efficiency in terms of the Levine number are provided. Geometries of a circular tube and planar channel are examined.     

Conditional reversible work method for molecular coarse graining applications

Systematically coarse grained models for complex fluids usually lack chemical and thermodynamic transferability. Efforts to improve transferability require the development of effective potentials with unequivocal physical significance. In this paper, we introduce conditional reversible work (CRW) potentials that describe nonbonded interactions in coarse grained models at the pair level. The method used to obtain these potentials is straightforward to implement, can be readily extended to compute hydration contributions in implicit-solvent potentials, and is easy to automize. As a first illustration of the method, we present CRW potentials for 3-site models of hexane and toluene. The temperature-transferability of the liquid phase density obtained with these potentials has been investigated, and a comparison has been made with effective potentials obtained by the iterative Boltzmann inversion method.     

Aggregation work at polydisperse micellization: ideal solution and "dressed micelle" models comparing to molecular dynamics simulations

General thermodynamic relations for the work of polydisperse micelle formation in the model of ideal solution of molecular aggregates in nonionic surfactant solution and the model of "dressed micelles" in ionic solution have been considered. In particular, the dependence of the aggregation work on the total concentration of nonionic surfactant has been analyzed. The analogous dependence for the work of formation of ionic aggregates has been examined with regard to existence of two variables of a state of an ionic aggregate, the aggregation numbers of surface active ions and counterions. To verify the thermodynamic models, the molecular dynamics simulations of micellization in nonionic and ionic surfactant solutions at two total surfactant concentrations have been performed. It was shown that for nonionic surfactants, even at relatively high total surfactant concentrations, the shape and behavior of the work of polydisperse micelle formation found within the model of the ideal solution at different total surfactant concentrations agrees fairly well with the numerical experiment. For ionic surfactant solutions, the numerical results indicate a strong screening of ionic aggregates by the bound counterions. This fact as well as independence of the coefficient in the law of mass action for ionic aggregates on total surfactant concentration and predictable behavior of the "waterfall" lines of surfaces of the aggregation work upholds the model of "dressed" ionic aggregates.     

Biomimetically constructing a hypoxia-activated programmable phototheranostics at the molecular level

The hypoxic microenvironment is considered the preponderant initiator to trigger a cascade of progression and metastasis of tumors, also being the major obstacle for oxygen consumption therapeutics, including photodynamic therapy (PDT). In this work, we report a programmable strategy at the molecular level to modulate the reciprocal interplay between tumor hypoxia, angiogenesis, and PDT outcomes by reinforcing synergistic action between a H₂O₂ scavenger, O₂ generator and photosensitizer. The modular combination of a catalase biomimetic (tri-manganese cryptand, 1) and a photosensitizer (Ce6) allowed the rational design of a cascade reaction beginning with dismutation of H₂O₂ to O₂ under hypoxic conditions to enhance photosensitization and finally photooxidation. Concurrently, this led to the decreased expression of the vascular endothelial growth factor (VEGF) and effectively reduced unwanted growth of blood vessels observed in the chick chorioallantois membrane (CAM). Notably, the proof-of-principle experiments using the tumor-bearing models proved successful in enhancing PDT efficacy, prolonging their life cycles, and improving immunity, which could be monitored by magnetic resonance imaging (MRI).

A programmable strategy at the molecular level to modulate the ratio of a catalyst and photosensitizer to maximize the collaborative efficiency of anti-angiogenesis and PDT.     

Observing Single Hollow Porous Carbon Catalyst Collisions for Oxygen Reduction at Gold Nanoband Electrode

The evaluation of single carbon particle catalysts is critical to better understand the relationship between structure and properties. Here, we use an electrochemical collision method to study the electrocatalytic behaviour of single hollow porous carbon catalyst on gold nanoband electrodes (AuNBE). We observed the catalytic current of oxygen reduction of single carbon particle and quantified the contribution of the porous structure to the catalytic performance. We find that the meso/microporous and hollow structures contribute to the electrocatalytic current. Our research provides direct evidence that the hollow/porous structures improve the electrocatalytic performance.