Conformational analysis of 18-azacrown-6 and its bonding with late first transition series divalent metals: insight from DFT combined with NPA and QTAIM analyses

Density functional theory calculations, together with quantum theory of atoms in molecules (QTAIM) analyses, have been performed to investigate 18-azacrown-6 complexes of the high-spin late first transition series divalent metal ions in the gas phase and, in some cases, in aqueous solution simulated by a polarizable continuum model. Six intramolecular H-H bonding interactions in the meso-complexes are found to arise from folding of the ligand upon its electrostatic interaction with the metal ions, which are largely absent in the lowest-energy C(2h) conformer of the free ligand. The ligand-to-metal charge transfer obtained from QTAIM analysis, among other things, is found to be an important factor that controls the stability of these complexes. The inter-relationship between the ligand preorganization energy, the zero-point corrected formation energy of the metal complexes, and the H-H bonding pair distances, as well as the dependence of the electron density and the total energy density at the H-H bond critical points on the H-H bonding pair distances, provides a physical basis for understanding and explaining the stabilizing nature of these closed-shell interactions, which are often viewed as steric clashes that lead to complex destabilization.     

Acid-base thermochemistry of gaseous oxygen and sulfur substituted amino acids (Ser, Thr, Cys, Met)

Acid-base thermochemistry of isolated amino acids containing oxygen or sulfur in their side chain (serine, threonine, cysteine and methionine) have been examined by quantum chemical computations. Density functional theory (DFT) was used, with B3LYP, B97-D and M06-2X functionals using the 6-31+G(d,p) basis set for geometry optimizations and the larger 6-311++G(3df,2p) basis set for energy computations. Composite methods CBS-QB3, G3B3, G4MP2 and G4 were applied to large sets of neutral, protonated and deprotonated conformers. Conformational analysis of these species, based on chemical approach and AMOEBA force field calculations, has been used to identify the lowest energy conformers and to estimate the population of conformers expected to be present at thermal equilibrium at 298 K. It is observed that G4, G4MP2, G3B3, CBS-QB3 composite methods and M06-2X DFT lead to similar conformer energies. Thermochemical parameters have been computed using either the most stable conformers or equilibrium populations of conformers. Comparison of experimental and theoretical proton affinities and Δ(acid)H shows that the G4 method provides the better agreement with deviations of less than 1.5 kJ mol(-1). From this point of view, a set of evaluated thermochemical quantities for serine, threonine, cysteine and methionine may be proposed: PA = 912, 919, 903, 938; GB = 878, 886, 870, 899; Δ(acid)H = 1393, 1391, 1396, 1411; Δ(acid)G = 1363, 1362, 1367, 1382 kJ mol(-1). This study also confirms that a non-negligible ΔpS° is associated with protonation of methionine and that the most acidic hydrogen of cysteine in the gas phase is that of the SH group. In several instances new conformers were identified thus suggesting a re-examination of several IRMPD spectra.     

Dissociation Channel Dependence on Peptide Size Observed in Electron Capture Dissociation of Tryptic Peptides

Electron capture dissociation (ECD) of a series of five residue peptides led to the observation that these small peptides did not lead to the formation of the usual c/z ECD fragments, but to a, b, y, and w fragments. In order to determine how general this behavior is for small sized peptides, the effect of peptide size on ECD fragments using a complete set of ECD spectra from the SwedECD spectra database was examined. Analysis of the database shows that b and w fragments are favored for small peptide sizes and that average fragment size shows a linear relationship to parent peptide size for most fragment types. From these data, it appears that most of the w fragments are not secondary fragments of the major z ions, in sharp contrast with the proposed mechanism leading to these ions. These data also show that c fragment distributions depend strongly on the nature of C-terminal residue basic site: arginine leads to loss of short neutral fragments, whereas lysine leads to loss of longer neutral fragments. It also appears that b ions might be produced by two different mechanisms depending on the parent peptide size. A model for the fragmentation pathways in competition is proposed. These relationships between average fragment size and parent peptide size could be further exploited also for CID fragment spectra and could be included in fragmentation prediction algorithms.     

A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald–Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the S_NAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest.     

Kinetics of poly(ethylene terephthalate) glycolysis by diethylene glycol. I. Evolution of liquid and solid phases

The kinetics of uncatalysed glycolysis, at 220 °C, of poly(ethylene terephthalate) (PET) by diethylene glycol (DEG) in high excess has been studied. An experimental device allowing good separation, at reaction temperature, of the solid and liquid phases was set up.The results suggest that PET is initially depolymerized in the slightly swollen solid phase, by glycolysis of the amorphous interlamellar chains. This mechanism continues until a solid phase of highly crystallized polyester is obtained.The internal tensions engendered by this chemical modification cause cracks, delamination and mechanical disintegration of the polymer. The transfer towards the liquid phase is then strongly accelerated and the solvolysis of the depolymerization products continues in the liquid phase, up to equilibrium.     

A Highly Effective Ruthenium System for the Catalyzed Dehydrogenative Cyclization of Amine–Boranes to Cyclic Boranes under Mild Conditions

We recently disclosed a new ruthenium‐catalyzed dehydrogenative cyclization process (CDC) of diamine–monoboranes leading to cyclic diaminoboranes. In the present study, the CDC reaction has been successfully extended to a larger number of diamine–monoboranes ( 4 – 7 ) and to one amine–borane alcohol precursor ( 8 ). The corresponding NB(H)N‐ and NB(H)O‐containing cyclic diaminoboranes ( 12 – 15 ) and oxazaborolidine ( 16 ) were obtained in good to high yields. Multiple substitution patterns on the starting amine–borane substrates were evaluated and the reaction was also performed with chiral substrates. Efforts have been spent to understand the mechanism of the ruthenium CDC process. In addition to a computational approach, a strategy enabling the kinetic discrimination on successive events of the catalytic process leading to the formation of the NB(H)N linkage was performed on the six‐carbon chain diamine–monoborane 21 and completed with a ¹⁵N NMR study. The long‐life bis‐σ‐borane ruthenium intermediate 23 possessing a reactive NHMe ending was characterized in situ and proved to catalyze the dehydrogenative cyclization of 1 , ascertaining that bis σ‐borane ruthenium complexes are key intermediates in the CDC process.     

Self‐Assembled Supramolecular Nanocarrier Hosting Two Kinds of Guests in the Site‐Isolation State

Hyperbranched polyethylenimine (HPEI) was simply mixed with a solution of amphiphilic calix[4]arene (AC4), which possesses four phenol groups and four aliphatic chains, in chloroform. This resulted in the novel supramolecular complex HPEI–AC4 through the noncovalent interaction of the amino groups of HPEI with the phenol groups of AC4. The formed HPEI–AC4 supramolecular complexes were characterized by ¹H NMR spectroscopy and dynamic light scattering. The cationic water‐soluble dye methyl blue (MB) and the anionic water‐soluble dye methyl orange (MO) were used as the model guests to test the performance of HPEI–AC4 as a supramolecular nanocarrier. It was found that HPEI–AC4 could accommodate the anionic water‐soluble MO guests into the HPEI core. The MO encapsulation capacity of HPEI–AC4 was pH sensitive, which reached maximum loading under weakly acidic conditions. The loaded MO molecules could be totally released when the pH value was reduced to be around 4.5 or raised to be around 9.5, and this process was reversible. HPEI–AC4 could not only accommodate the anionic MO with the HPEI core but could also simultaneously load the cationic MB molecules using the formed AC4 shell, thereby realizing the site isolation of the two kinds of functional units. The amount of MO and MB encapsulated by HPEI–AC4 could be controlled by varying the ratio of hydroxyl groups of AC4 to amino groups of HPEI.