Through-Space Polar-π Interactions in 2,6-Diarylthiophenols

Molecular recognition between polar groups and aromatic molecules is fundamentally important to rational drug design. Although it has been well established that many polar functionalities interact with electron-rich aromatic residues through energetically favorable polar-π interactions, there is a limited understanding of the association between thiols and aromatic systems. Herein we report physical-organic chemistry studies on 2,6-diarylthiophenols that possess the central thiophenol ring and two flanking aromatic rings with tunable electronic properties caused by substituents at distant para position. Hammett analysis revealed that pK_a values and proton affinities correlate well with Hammett sigma values of substituents. Additional energy decomposition analysis supported the conclusion that both through-space SH-π interactions and S⁻-π interactions contribute to intramolecular stabilization of 2,6-diarylthiophenols.     

Gold-Catalyzed C(sp2)−C(sp) Coupling by Alkynylation through Oxidative Addition of Bromoalkynes

A gold(I)-catalyzed cascade cyclization–alkynylation of allenoates using alkynyl bromide to generate β-alkynyl-γ-butenolides was investigated. Whereas alkynyl iodides afforded significant amounts of the homo-coupling of two lactone units, alkynyl bromides led to a selective reaction, and a broad functional group tolerance was observed. Under the optimized reaction conditions, it was possible to directly synthesize a large range of β-alkynyl-γ-butenolides in moderate to good yields without the need for any external oxidant.     

Rhodamines with a Chloronicotinic Acid Fragment for Live Cell Superresolution STED Microscopy**

Formylation of 2,6-dichloro-5-R-nicotinic acids at C-4 followed by condensation with 3-hydroxy-N,N-dimethylaniline gave analogs of the popular TAMRA fluorescent dye with a 2,6-dichloro-5-R-nicotinic acid residues (R=H, F). The following reaction with thioglycolic acid is selective, involves only one chlorine atom at the carbon between pyridine nitrogen and the carboxylic acid group and affords new rhodamine dyes absorbing at 564/ 573 nm and emitting at 584/ 597 nm (R=H/ F, in aq. PBS). Conjugates of the dyes with “small molecules” provided specific labeling (covalent and non-covalent) of organelles as well as of components of the cytoskeleton in living cells and were combined with fluorescent probes prepared from 610CP and SiR dyes and applied in two-color STED microscopy with a 775 nm STED laser.     

Electronic and geometric characterization of the L-cysteine paired-row phase on Au(110)

We have studied the vapor-phase deposition of L-cysteine on the Au(110) surface by means of synchrotron-based techniques. Relying on a comparison with previous X-ray photoemission analysis, we have assigned the fine structure of the C K-shell X-ray absorption spectra to the nonequivalent carbon bonds within the molecule. In particular, the C1s --> sigma* transition, where the sigma* state is mainly localized on the C-S bond, is shifted well below the ionization threshold, at approximately -5 eV from the characteristic pi* transition line related to carboxylic group. From the polarization dependence of the absorption spectra in the monolayer coverage range, the molecules are found to lay flat on the surface with both the C-S bond and the carboxylic group almost parallel to the surface. We performed in situ complementary surface X-ray diffraction, SXRD, measurements to probe the rearrangement of the Au atoms beneath the L-cysteine molecules. Since the early stage of deposition, L-cysteine domains are formed which display an intermediate fourfold symmetry along [001]. The self-assembly of molecules into paired rows, extending along the [1(-)10] direction, is fully compatible with our observations, as has been reported for the case of D-cysteine molecules grown on Au(110) [Kühnle, A. et al. Phys. Rev. Lett. 2004, 93, 086101.]     

Torus Actions in the Normalization Problem

Let f be a germ of biholomorphism of ℂ ⁿ , fixing the origin. We show that if the germ commutes with a torus action, then we get information on the germs that can be conjugated to f, and furthermore on the existence of a holomorphic linearization or of a holomorphic normalization of f. We find out in a complete and computable manner what kind of structure a torus action must have in order to get a Poincaré-Dulac holomorphic normalization, studying the possible torsion phenomena. In particular, we link the eigenvalues of df _O to the weight matrix of the action. The link and the structure we found are more complicated than what one would expect; a detailed study was needed to completely understand the relations between torus actions, holomorphic Poincaré-Dulac normalizations, and torsion phenomena. We end the article giving an example of techniques that can be used to construct torus actions.     

Immobilized penicillin G acylase as reactor and chiral selector in liquid chromatography

In this paper, the use of penicillin G acylase (PGA) as a biocatalyst and as a chiral selector is described. Penicillin G-acylase is an interesting enzyme used in the manufacture of semisynthetic antibiotics and, in particular, in the production of 6-APA by hydrolysis of penicillin G. Five PGA-based HPLC columns have been prepared by using two different silica supports by employing two immobilization methods, namely "in situ" and "in batch". The effects of the immobilization techniques and of different silica pore size on the catalytic properties of the enzyme as well as the applicability of the PGA-bonded stationary phases as chiral selectors for a number of chiral drugs have been investigated. The HPLC columns based on immobilized PGA combine the hydrolytic activity and the chiral recognition properties of PGA, therefore they have been used for the development of a combined reaction-separation system for chiral and achiral substrates.     

Probing the Lewis Acidity of Boronic Acids through Interactions with Arene Substituents

Boronic acids are Lewis acids that exist in equilibrium with boronate forms in aqueous solution. Here we experimentally and computationally investigated the Lewis acidity of 2,6-diarylphenylboronic acids; specially designed phenylboronic acids that possess two flanking aromatic rings with tunable aromatic character. Hammett analysis of 2,6-diarylphenylboronic acids reveals that their Lewis acidity remains unchanged upon the introduction of EWG/EDG at the distant para position of the flanking aromatic rings. Structural and computational studies demonstrate that polar-π interactions and solvation effects contribute to the stabilization of boronic acids and boronate forms by aromatic rings. Our physical-organic chemistry work highlights that boronic acids and boronates can be stabilized by aromatic systems, leading to an important molecular knowledge for rational design and development of boronic acid-based catalysts and inhibitors of biomedically important proteins.