Anion binding studies of fluorinated expanded calixpyrroles

The anion binding properties of fluorinated calix[n]pyrroles (n = 4-6) in aprotic solvents (acetonitrile and DMSO) and modified reaction conditions allowing for the synthesis and isolation of the hitherto missing dodecafluorocalix[6]pyrrole from the condensation of 3,4-difluoro-1H-pyrrole and acetone are described. In acetonitrile solution containing 2% water, the association constants for the 1:1 binding interaction between octafluorocalix[4]pyrrole and chloride anion obtained with isothermal titration calorimetry (ITC) and (1)H NMR titration methods were found to match reasonably well. As compared to its nonfluorinated congener, octafluorocalix[4]pyrrole was found to display enhanced binding affinities for several representative anions in pure acetonitrile as judged from ITC analyses. Similar analyses of the fluorinated calix[n]pyrroles revealed an increase in the relative affinity for bromide over chloride with increasing macrocycle size, as manifest in a decrease in the binding ratio K(a(Cl))/K(a(Br)). Anion binding studies in the solid state, involving single-crystal X-ray diffraction analyses of the chloride and acetate anion complexes of octafluorocalix[4]pyrrole and decafluorocalix[5]pyrrole, respectively, confirmed the expected hydrogen bond interactions between the pyrrolic NH protons and the bound anions.     

A CSOV study of the difference between HF and DFT intermolecular interaction energy values: the importance of the charge transfer contribution

Intermolecular interaction energy decompositions using the Constrained Space Orbital Variation (CSOV) method are carried out at the Hartree-Fock level on the one hand and using DFT with usual GGA functionals on the other for a number of model complexes to analyze the role of electron correlation in the intermolecular stabilization energy. In addition to the overall stabilization, the results provide information on the variation, with respect to the computational level, of the different contributions to the interaction energy. The complexes studied are the water linear dimer, the N-methylformamide dimer, the nucleic acid base pairs, the benzene-methane and benzene-N2 van der Waals complexes, [Cu+ -(ImH)3]2, where "ImH" stands for the Imidazole ligand, and ImH-Zn++. The variation of the frozen core energy (the sum of the intermolecular electrostatic energy and the Pauli repulsion energy) calculated from the unperturbed orbitals of the interacting entities indicates that the intramolecular correlation contributions can be stabilizing as well as destabilizing, and that general trends can be derived from the results obtained using usual density functionals. The most important difference between the values obtained from HF and DFT computations concerns the charge transfer contribution, which, in most cases, undergoes the largest increase. The physical meaning of these results is discussed. The present work gives reference calculations that might be used to parametrize new correlated molecular mechanics potentials.     

Anion transfer at a micro-water/1,2-dichloroethane interface facilitated by beta-octafluoro-meso-octamethylcalix[4]pyrrole

The facilitated transfer of four hydrophilic anions, i.e., Cl-, Br-, NO2-, and CH3CO2-, at the micro-water/1,2-dichloroethane interface supported at the tip of a micropipet has been observed successfully using beta-octafluoro-meso-octamethylcalix[4]pyrrole 2 as the receptor. We have also shown for the first time that the dynamics of this process can be studied by micropipet voltammetry. The standard kinetic rate constants (kdegrees) for facilitated anion transfer at such an interface were determined to be (2.11 +/- 0.90) x 10(-2) and (0.75 +/- 0.50) x 10(-2) cm/s in the case of Cl- and CH3CO2-, respectively. These values are much smaller than those associated with the facilitated transfer of analogous alkali metal ions. This difference is thought to reflect a number of underlying factors, including the higher hydration of anions as compared to similar sized cations. Studies such as these are expected to be useful in understanding the mechanism of anion transport at soft interfaces and for the design of yet-improved anion receptors and carriers.     

Poly(methyl methacrylate)s with pendant calixpyrroles: polymeric extractants for halide anion salts

Poly(methyl methacrylate)s containing pendant octamethylcalix[4]pyrrole subunits were prepared and demonstrated to be capable of extracting tetrabutylammonium chloride and fluoride salts from aqueous media.     

Oxidative rearrangements of isobenzofurans: studies toward the synthesis of the ajudazols

We present a new facet of isobenzofuran chemistry which allows for its efficient manipulation to generate biologically relevant entities. This methodology has been successfully applied toward the synthesis of ajudazol A.     

Recent advances in biomimetic natural product synthesis

This review highlights some of the most elegant and instructive biomimetic syntheses of natural products over the last few years, providing an updated overview of this area of research.     

Synthesis of conformationally locked versions of puromycin analogues

Conformationally locked North and South versions of puromycin analogues built on a bicyclo[3.1.0]hexane pseudosugar template were synthesized. The final assembly of the products was accomplished by the Staudinger-Vilarrasa coupling of the corresponding North (2 and 3) and South (6 and 7) 3'-azidopurine carbanucleosides with the Fmoc-protected 1-hydroxybenzotriazole ester of 4-methoxy-L-tyrosine. North azides 2 and 3 were reported earlier. The 3'-azido intermediates 6 and 7 that are necessary for the synthesis of the South puromycin analogues are described herein for the first time.     

Enhanced anion exchange for selective sulfate extraction: overcoming the Hofmeister bias

In this communication, a new approach to enhancing the efficacy of liquid-liquid anion exchange is demonstrated. It involves the concurrent use of appropriately chosen hydrogen-bond-donating (HBD) anion receptors in combination with a traditional quaternary ammonium extractant. The fluorinated calixpyrroles 1 and 2 and the tetraamide macrocycle 4 were found to be particularly effective receptors. Specifically, their use allowed the extraction of sulfate by tricaprylmethylammonium nitrate to be effected in the presence of excess nitrate. As such, the present work provides a rare demonstration of overcoming the Hofmeister bias in a competitive environment and the first to the authors' knowledge wherein this difficult-to-achieve objective is attained using a neutral HBD-based anion binding agent under conditions of solvent extraction.     

Nanoparticle Tracking Analysis of Polymer Nanoparticles in Blood Plasma

A successful drug delivery system must overcome complex biological barriers. For particles injected into the blood, one of the first and most critical barriers pertains to blood stability to circulate through the human body. To effectively design drug delivery vehicles, interactions between the particles and blood, as well as the aggregation behavior, must be understood. This work presents a method to analyze particle size and aggregation in blood plasma using a commercially available nanoparticle tracking analysis (NTA) system. As a model system, fluorescently labeled polystyrene nanoparticles are incubated in goat blood plasma and analyzed using NTA. The particles incubated in plasma are found to have a protein corona that is larger than what has been observed by dynamic light scattering (DLS) in diluted plasma. Particles that are decorated with a PEG layer are also found to have large protein coronas in undiluted plasma. Because NTA is based on a unique visualization method, large multicomponent aggregates could be observed and quantified in a manner not feasible with other techniques. PEGylation of the particles is found to decrease the multicomponent aggregation from 1000 ± 200 particles for unmodified to 200 ± 30 particles for 1K PEGylated per 1 × 10⁵ total particles.     

Synthesis of conformationally North-locked pyrimidine nucleosides built on an oxabicyclo[3.1.0]hexane scaffold

Beginning with a known 3-oxabicyclo[3.1.0]hexane scaffold (I), the relocation of the fused cyclopropane ring bond and the shifting of the oxygen atom to an alternative location engendered a new 2-oxabicyclo[3.1.0]hexane template (II) that mimics more closely the tetrahydrofuran ring of conventional nucleosides. The synthesis of this new class of locked nucleosides involved a novel approach that required the isocyanate II (B = NCO) with a hydroxyl-protected scaffold as a pivotal intermediate that was obtained in 11 steps from a known dihydrofuran precursor. The completion of the nucleobases was successfully achieved by quenching the isocyanate with the lithium salts of the corresponding acrylic amides that led to the uracil and thymidine precursors in a single step. Ring closure of these intermediates led to the target, locked nucleosides. The anti-HIV activity of 29 (uridine analogue), 31 (thymidine analogue), and 34 (cytidine analogue) was explored in human osteosarcoma (HOS) cells or modified HOS cells (HOS-313) expressing the herpes simplex virus 1 thymidine kinase (HSV-1 TK). Only the cytidine analogue showed moderate activity in HOS-313 cells, which means that the compounds are not good substrates for the cellular kinases.