Ultrafast photoinduced electron transfer within a self-assembled donor-acceptor system

A photoactive supramolecular assembly that is based on the hydrogen-bonded system H1.G2, consisting of a methyl viologen-functionalized barbiturate host (H1) (1-(N-(3,5-bis[[(6-tert-butylacetylamino-2-pyridyl)amino]carbonyl])-phenylacetamide)-1'-methyl-4,4'-bipyridium) and a [Re(Br)(CO)3(barbi-bpy)] (barbi-bpy = 5-[4-(4'-methyl)-2,2'-bipyridyl]methyl-2,4,6-(1H,3H,5H)-pyrimidinetrione) complex as the guest (G2) is described. The host molecule contains a well-known electron accepting group (methyl viologen), whereas the guest system can act as an efficient electron donor in the excited state. Upon self-assembly, the resulting adduct (H1.G2) represents an interesting noncovalently linked donor-acceptor system. The H1.G2 complex has been characterized in acetonitrile-d3 using 1H NMR and diffusion-ordered NMR spectroscopy (DOSY). The photophysical properties of the components and of the assembly have been studied in dichloromethane, in which the assembly has a high binding constant (Kass > or = 2 x 10(5) M(-1)), using time-resolved fluorescence and transient absorption spectroscopy. A detailed investigation of the hydrogen-bonded complex H1.G2 revealed that, upon excitation of the rhenium compound G2, an ultrafast electron-transfer process occurs from the metal-based component to the acceptor unit. The kinetics of the forward and back electron-transfer processes have been determined.     

Efficient One-Step Passivation of Polyurethane Using Transurethanization

The uncontrolled accumulation of biological materials on the surface of medical devices through protein adsorption or cell adhesion causes adverse biological reactions in the living host system, leading to complications. In this study, poly(ethylene glycol) (PEG) is successfully grafted onto polyurethane (PU) surfaces by using a new strategy through a simple and efficient transurethanization reaction. The PEG hydroxyl group is deprotonated and then reacted with the PU surface to provide antiadhesive hydrophilic surfaces in a single step. Surface analysis techniques proved the grafting to be efficient and the formation of a hydrophilic polymeric layer at the surface of PU. Biological assays showed that the surface modification induced lower protein adsorption, cell, platelet, and bacterial adhesion than untreated surfaces, showing a potential for biomedical applications.     

Strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers by native chemical ligation

A strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers by native chemical ligation using poly(lysine) dendritic wedges as scaffolds is presented.     

Enantioselective Approach for Expanding the Three-Dimensional Space of Tetrahydroquinoline to Develop BET Bromodomain Inhibitors**

The pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline-catalyzed Mannich reaction followed by the addition of BF₃ ⋅ OEt₂, which generates a highly electrophilic aza-ortho-quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one-pot process provides access for the first time to tetrahydroquinolines with a cis-2,3 and trans-3,4 configuration. As proof of concept, we demonstrate that a three-step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2-selective BET bromodomain inhibitor with anti-inflammatory effect.     

Designing light-driven rotary molecular motors

The ability to induce and amplify motion at the molecular scale has seen tremendous progress ranging from simple molecular rotors to responsive materials. In the two decades since the discovery of light-driven rotary molecular motors, the development of these molecules has been extensive; moving from the realm of molecular chemistry to integration into dynamic molecular systems. They have been identified as actuators holding great potential to precisely control the dynamics of nanoscale devices, but integrating molecular motors effectively into evermore complex artificial molecular machinery is not trivial. Maximising efficiency without compromising function requires conscious and judicious selection of the structures used. In this perspective, we focus on the key aspects of motor design and discuss how to manipulate these properties without impeding motor integrity. Herein, we describe these principles in the context of molecular rotary motors featuring a central double bond axle and emphasise the strengths and weaknesses of each design, providing a comprehensive evaluation of all artificial light-driven rotary motor scaffolds currently present in the literature. Based on this discussion, we will explore the trajectory of research into the field of molecular motors in the coming years, including challenges to be addressed, potential applications, and future prospects.

Various families of light-driven rotary molecular motors and the key aspects of motor design are discussed. Comparisons are made between the strengths and weaknesses of each motor. Challenges, applications, and future prospects are explored.     

Psoromic acid is a selective and covalent Rab-prenylation inhibitor targeting autoinhibited RabGGTase

Post-translational attachment of geranylgeranyl isoprenoids to Rab GTPases, the key organizers of intracellular vesicular transport, is essential for their function. Rab geranylgeranyl transferase (RabGGTase) is responsible for prenylation of Rab proteins. Recently, RabGGTase inhibitors have been proposed to be potential therapeutics for treatment of cancer and osteoporosis. However, the development of RabGGTase selective inhibitors is complicated by its structural and functional similarity to other protein prenyltransferases. Herein we report identification of the natural product psoromic acid (PA) that potently and selectively inhibits RabGGTase with an IC(50) of 1.3 μM. Structure-activity relationship analysis suggested a minimal structure involving the depsidone core with a 3-hydroxyl and 4-aldehyde motif for binding to RabGGTase. Analysis of the crystal structure of the RabGGTase:PA complex revealed that PA forms largely hydrophobic interactions with the isoprenoid binding site of RabGGTase and that it attaches covalently to the N-terminus of the α subunit. We found that in contrast to other protein prenyltransferases, RabGGTase is autoinhibited through N-terminal (α)His2 coordination with the catalytic zinc ion. Mutation of (α)His dramatically enhances the reaction rate, indicating that the activity of RabGGTase is likely regulated in vivo. The covalent binding of PA to the N-terminus of the RabGGTase α subunit seems to potentiate its interaction with the active site and explains the selectivity of PA for RabGGTase. Therefore, psoromic acid provides a new starting point for the development of selective RabGGTase inhibitors.     

Words and Polynomial Invariants of Finite Groups in Non-Commutative Variables

Let V be a complex vector space with basis {x ₁, x ₂, . . . , x _n } and G be a finite subgroup of GL(V). The tensor algebra T(V) over the complex is isomorphic to the polynomials in the non-commutative variables x ₁, x ₂, . . . , x _n with complex coefficients. We want to give a combinatorial interpretation for the decomposition of T(V) into simple G-modules. In particular, we want to study the graded space of invariants in T(V) with respect to the action of G. We give a general method for decomposing the space T(V) into simple modules in terms of words in a Cayley graph of the group G. To apply the method to a particular group, we require a homomorphism from a subalgebra of the group algebra into the character algebra. In the case of G as the symmetric group, we give an example of this homomorphism from the descent algebra. When G is the dihedral group, we have a realization of the character algebra as a subalgebra of the group algebra. In those two cases, we have an interpretation for the graded dimensions and the number of free generators of the algebras of invariants in terms of those words.     

Mid-infrared spectroscopy of molecular ions in helium nanodroplets

High resolution IR spectra of aniline, styrene, and 1,1-diphenylethylene cations embedded in superfluid helium nanodroplets have been recorded in the 300-1700 cm(-1) range using a free-electron laser as radiation source. Comparison of the spectra with available gas phase data reveals that the helium environment induces no significant matrix shift nor leads to an observable line broadening of the resonances. In addition, the IR spectra have provided new and improved vibrational transition frequencies for the cations investigated, as well as for neutral aniline and styrene. Indications have been found that the ions desolvate from the droplets after excitation by a non-evaporative process in which they are ejected from the helium droplets. The kinetic energy of the ejected ions is found to be ion specific and to depend only weakly on the excitation energy.