Cooperativity and tunable excited state deactivation: modular self-assembly of depsipeptide dendrons on a Hamilton receptor modified porphyrin platform

A series of novel supramolecular architectures were built around a tin tetraphenyl porphyrin platform 6--functionalized by a 2-fold 1-ethyl-3-3-(3-dimethylaminopropyl)carbodiimide (EDC) promoted condensation reaction--and chiral depsipeptide dendrons of different generations 1-4. Here, implementation of a Hamilton receptor provided the necessary means to keep the constituents together via strong hydrogen bonding. Characterization of all architectures has been performed, including 4 which is the fourth generation, on the basis of NMR and photophysical methods. In particular, several titration experiments were conducted suggesting positive cooperativity, an assessment that is based on association constants that tend to be higher for the second binding step than for the first step. Importantly, molecular modeling calculations reveal a significant deaggregation of the intermolecular network of 6 during the course of the first binding step. As a consequence, an improved accessibility of the second Hamilton receptor unit in 6 emerges and, in turn, facilitates the higher association constants. The features of the equilibrium, that is, the dynamic exchange of depsipeptide dendrons 1-4 with fullerene 5, was tested in photophysical reference experiments. These steady-state and time-resolved measurements showed the tunable excited-state deactivations of these complexes upon photoexcitation.     

A selective convenient ruthenium-mediated synthesis of mixed acetals

Addition of alcohols and phenols to allyl ethers catalyzed mainly by ruthenium complexes was studied. Complexes of ruthenium generated in situ from precursors such as {[RuCl₂(1,5-COD)]_x} or [Ru₃(CO)₁₂] and from external ligands such as phosphines (e.g. PPh₃, PBu₃, BINAP) or phosphites (e.g. P(OPh)₃, P(OMe)₃) were found to be particularly efficient catalysts of the studied reactions. Transacetalization reaction could be practically completely eliminated by the addition of a base (particularly Na₂CO₃) to the catalytic systems. It was observed that the selectivity of mixed acetals formation increases with increasing value of Θ parameter of phosphines. Especially interesting results (0–5% of transacetalization) have been obtained for catalytic systems generated from {[RuCl₂(1,5-COD)]_x} or [Ru₃(CO)₁₂], phosphines (PPh₃, BINAP, dppe, tris(2,4,6-tri-metylphenyl)phosphine, or dppf) and Na₂CO₃. The mechanism of mixed acetals formation has been investigated using deuterated reagents. It is postulated that the examined reaction is a nucleophilic addition of ROH to a hydrido-π-allyl complex formed during oxidative addition of allyl substrate to metal complex. As a result, a new, selective, and convenient method of the synthesis of symmetrical and, in particular, unsymmetrical (mixed) acetals has been developed. Mixed acetals CH₃CH₂CH(OR¹)(OR²) may be obtained in the reaction of R¹-O-allyl with R²OH or R¹OH with R²-O-allyl, depending on the structure of R¹ and R².     

The nitrogen inversion in fused isoxazolidinyl derivatives of substituted uracil: synthesis,NMR and computational analysis

A series of fused isoxazolidines have been prepared via 1,3-dipolar cycloaddition reactions of N-protected methylenenitrones with 1,3-dimethyluracil derivatives, and their NMR spectra have been recorded in TFA-d and in CDCl₃ over a wide range of temperatures. The spectra indicate the presence of two invertomers for all isoxazolidines. Barriers to nitrogen inversion in the cycloadduct 6a have been determined using DFT quantochemical calculations. Our estimates have shown that the inversion proceeds at more complex path, involving four structures of local minima and four transition states.

     

Divergence Entropy-Based Evaluation of Hydrophobic Core in Aggressive and Resistant Forms of Transthyretin

The two forms of transthyretin differing slightly in the tertiary structure, despite the presence of five mutations, show radically different properties in terms of susceptibility to the amyloid transformation process. These two forms of transthyretin are the object of analysis. The search for the sources of these differences was carried out by means of a comparative analysis of the structure of these molecules in their native and early intermediate stage forms in the folding process. The criterion for assessing the degree of similarity and differences is the status of the hydrophobic core. The comparison of the level of arrangement of the hydrophobic core and its initial stages is possible thanks to the application of divergence entropy for the early intermediate stage and for the final forms. It was shown that the minimal differences observed in the structure of the hydrophobic core of the forms available in PDB, turned out to be significantly different in the early stage (ES) structure in folding process. The determined values of divergence entropy for both ES forms indicate the presence of the seed of hydrophobic core only in the form resistant to amyloid transformation. In the form of aggressively undergoing amyloid transformation, the structure lacking such a seed is revealed, being a stretched one with a high content of β-type structure. In the discussed case, the active presence of water in the structural transformation of proteins expressed in the fuzzy oil drop model (FOD) is of decisive importance for the generation of the final protein structure. It has been shown that the resistant form tends to generate a centric hydrophobic core with the possibility of creating a globular structure, i.e., a spherical micelle-like form. The aggressively transforming form reveals in the structure of its early intermediate, a tendency to form the ribbon-like micelle as observed in amyloid.     

Streak patterns in binary granular media in a rotating drum

The Discrete Element Method (DEM) is used to understand the formation of radial streak patterns produced when binary granular material (which may differ either in size, density or shape) segregate in a slowly rotating drum. Our simulations show that initial streak formation requires temporal fluctuations in the particle bed’s strength. This, in turn, creates fluctuations in the slope and shape of the upper surface of the bed which control the particle avalanches down the free surface. These ultimately lead to streak formation. We conjecture that growth and stabilisation of a regular streak pattern requires the two sets of particles to have significantly different angles of repose.     

New heteroleptic bis-phenanthroline copper(I) complexes with dipyridophenazine or imidazole fused phenanthroline ligands: spectral, electrochemical, and quantum chemical studies

Two new sterically challenged diimine ligands L(1) (2,9-dimesityl-2-(4'-bromophenyl)imidazo[4,5-f][1,10]phenanthroline) and L(2) (3,6-di-n-butyl-11-bromodipyrido[3,2-a:2',3'-c]phenazine) have been synthesized with the aim to build original heteroleptic copper(I) complexes, following the HETPHEN concept developed by Schmittel and co-workers. The structure of L(1) is based on a phen-imidazole molecular core, derivatized by two highly bulky mesityl groups in positions 2 and 9 of the phenanthroline cavity, preventing the formation of a homoleptic species, while L(2) is a dppz derivative, bearing n-butyl chains in α positions of the chelating nitrogen atoms. The unambiguous formation of six novel heteroleptic copper(I) complexes based on L(1), L(2), and complementary matching ligands (2,9-R(2)-1,10-phenanthroline, with R = H, methyl, n-butyl or mesityl) has been evidenced, and the resulting compounds were fully characterized. The electronic absorption spectra of all complexes fits well with DFT calculations allowing the assignment of the main transitions. The characteristics of the emissive excited state were investigated in different solvents using time-resolved single photon counting and transient absorption spectroscopy. The complexes with ligand L(2), bearing a characteristic dppz moiety, exhibit a very low energy excited-state which mainly leads to fast nonradiative relaxation, whereas the emission lifetime is higher for those containing the bulky ligand L(1). For example, a luminescence quantum yield of about 3 × 10(-4) is obtained with a decay time of about 50 ns for C2 ([Cu(I)(nBu-phen)(L(1))](+)) with a weak influence of strong coordinating solvent on the luminescence properties. Overall, the spectral features are those expected for a highly constrained coordination cage. Yet, the complexes are stable in solution, partly due to the beneficial π stacking between mesityl groups and vicinal phenanthroline aromatic rings, as evidenced by the X-ray structure of complex C3 ([Cu(I)(Mes-phen)(L(2))](+)). Electrochemistry of the copper(I) complexes revealed reversible anodic behavior, corresponding to a copper(I) to copper(II) transition. The half wave potentials increase with the steric bulk at the level of the copper(I) ion, reaching a value as high as 1 V vs SCE, with the assistance of ligand induced electronic effects. L(1) and L(2) are further end-capped by a bromo functionality. A Suzuki cross-coupling reaction was directly performed on the complexes, in spite of the handicapping lability of copper(I)-phenanthroline complexes.     

Naphthalene-fused metallo-porphyrins--synthesis and spectroscopy

Oxidative aromatic coupling of meso-substituted porphyrins bearing one electron-rich naphthalene unit has been studied in detail. After thorough optimization of oxidant, naphthalene-fused porphyrins were prepared in high yield without contamination from chlorinated side-products using Fe(ClO(4))(3)·2H(2)O. Copper and nickel complexes were successfully transformed into π-expanded porphyrins in 40-83% yield.     

Complexes of lanthanide nitrates with tri tert butylphosphine oxide

Reaction of lanthanide nitrates with (t)Bu(3)PO (=L) lead to the isolation of complexes Ln(NO(3))(3)L(2)·H(2)O·nEtOH (Ln = La (1), Nd(2)), Ln(NO(3))(3)L(2)?·nEtOH (Sm(3), Eu(4)), and Ln(NO(3))(3)L(2) (Dy(5), Er(6), Lu(7)). These have been characterized by elemental analysis, infrared and NMR((1)H, (13)C and (31)P) spectroscopy and single-crystal X-ray diffraction. The structures show L to be positioned on opposite sides of the metal with the nitrates forming an equatorial band. When Ln = Dy, Er, and Lu two distinct molecules are present in the unit cell. A major isomer (70%) has a (P)O-Ln-O(P) angle of less than 180° with one of the nitrate ligands twisted out of the plane of the other nitrates while the lower abundance isomer is more symmetric with the (P)O-Ln-O(P) angle of 180° and the nitrate ligands coplanar giving a hexagonal bipyramidal geometry. These isomers cannot be observed by variable temperature solution (31)P NMR measurements but are clearly seen in the solid-state NMR spectrum of the Lu complex. Variable temperature solid-state NMR indicates that the isomers do not interconvert at temperatures up to 100 °C. Attempts to prepare cationic species [Ln(NO(3))(2)L(3)](+)[PF(6)](-) have not been totally successful and led to the isolation of crystals of Lu(NO(3))(3)L(2) and Tb(NO(3))(3)L(2).CH(3)CN (8).     

Design and development of a field-deployable single-molecule detector (SMD) for the analysis of molecular markers

Single-molecule detection (SMD) has demonstrated some attractive benefits for many types of biomolecular analyses including enhanced processing speed by eliminating processing steps, elimination of ensemble averaging and single-molecule sensitivity. However, it's wide spread use has been hampered by the complex instrumentation required for its implementation when using fluorescence as the readout modality. We report herein a simple and compact fluorescence single-molecule instrument that is straightforward to operate and consisted of fiber optics directly coupled to a microfluidic device. The integrated fiber optics served as waveguides to deliver the laser excitation light to the sample and collecting the resulting emission, simplifying the optical requirements associated with traditional SMD instruments by eliminating the need for optical alignment and simplification of the optical train. Additionally, the use of a vertical cavity surface emitting laser and a single photon avalanche diode serving as the excitation source and photon transducer, respectively, as well as a field programmable gate array (FPGA) integrated into the processing electronics assisted in reducing the instrument footprint. This small footprint SMD platform was tested using fluorescent microspheres and single AlexaFluor 660 molecules to determine the optimal operating parameters and system performance. As a demonstration of the utility of this instrument for biomolecular analyses, molecular beacons (MBs) were designed to probe bacterial cells for the gene encoding Gram-positive species. The ability to monitor biomarkers using this simple and portable instrument will have a number of important applications, such as strain-specific detection of pathogenic bacteria or the molecular diagnosis of diseases requiring rapid turn-around-times directly at the point-of-use.     

Semipinacol rearrangement of cis-fused β-lactam diols into keto-bridged bicyclic lactams

The 6-azabicyclo[3.2.1]octane ring system, prevalent in a range of biologically active molecules, is prepared through a novel semipinacol rearrangement utilizing a cyclic phosphorane or sulfite intermediate. The rearrangement proceeds with exclusive N-acyl group migration of a β-lactam ring and results in carbonyl functionality at the 7- and bridging 8-position of the bicycle. Precursor ring-fused β-lactam diols are prepared through a sequence of 4-exo trig carbamoyl radical cyclization, regioselective dithiocarbamate group elimination, and dihydroxylation.