Diarylamines with the neighboring pyridyl group: synthesis and modulation of the amine functionality via intramolecular H-bonding

New pyridyl-containing diarylamines were obtained via Cu-assisted reductive amination of the ortho-2-pyridylaryl boronic acids. Comparative analysis of the spectral and electrochemical data obtained for new diarylamines and their pyridyl-free counterparts revealed the intramolecular H-bond (IMHB) formation which significantly influences the properties of the amino group. The electron density at the N atom of the amino group is increased due to partial weakening of the N-H bond, although the BDE and activation energy for the H-atom abstraction is increased due to the chelating effect of two N atoms. The ortho-pyridyl-containing diarylamines are more prone to be oxidized as compared to their pyridyl-free counterparts; the shift in the oxidation potential values correlates with the strength of the intramolecular H-bonding which can be tuned by inserting substituents in the pyridyl or phenyl rings. The IMHB is reserved even in polar solvents having a significant H-acceptor ability (such as DMSO) but can be destroyed in methanol, testifying in favor of the dynamic nature of the H-bonding.

In silico investigation of ligand-regulated palladium-catalysed formic acid dehydrative decomposition under acidic conditions

In silico investigation of ligand-regulated palladium-catalysed formic acid dehydrative decomposition to carbon monoxide under acidic conditions was conducted. Two types of bidentate tertiary phosphine ligands were selected on the basis of previous experimental study. And the promoting effect of para-toluenesulfonic acid (PTSA) was specifically investigated. The pyridyl group implanted in pytbpx ligand is found to mainly contribute on enhancing the activity of palladium catalyst. The PTSA promoter displays specific role for regenerating active species and supressing dehydrogenation during Pd-pytbpx/Pd-dtbpx catalysed dehydration process. CO releasing process catalysed by Pd-dtbpx also facilitated by adding PTSA. According to the mechanism hereby supposed, introducing electron-withdrawing substitution at para-position of pyridyl rings may further improve the dehydrative decomposition activity of Pd-pytbpx.

In silico investigation of ligand-regulated palladium-catalysed formic acid dehydrative decomposition under acidic conditions

In silico investigation of ligand-regulated palladium-catalysed formic acid dehydrative decomposition to carbon monoxide under acidic conditions was conducted. The contribution from the pyridyl group implanted in pytbpx ligand on enhancing the activity of palladium catalyst and the specific role of para-toluenesulfonic acid as the promoter of dehydration were uncovered.

In silico investigation of ligand-regulated palladium-catalysed formic acid dehydrative decomposition under acidic conditions

In silico investigation of ligand-regulated palladium-catalysed formic acid dehydrative decomposition to carbon monoxide under acidic conditions was conducted. The contribution from the pyridyl group implanted in pytbpx ligand on enhancing the activity of palladium catalyst and the specific role of para-toluenesulfonic acid as the promoter of dehydration were uncovered.

Controlling Topology within Halogen-Bonded Networks by Varying the Regiochemistry of the Cyclobutane-Based Nodes

The formation of a pair of extended networks sustained by halogen bonds based upon two regioisomers of a photoproduct, namely rctt-1,3-bis(4-pyridyl)-2,4-bis(phenyl)cyclobutane (ht-PP) and rctt-1,2-bis(4-pyridyl)-3,4-bis(phenyl)cyclobutane (hh-PP), that have varied topology is reported. These networks are held together via I⋯N halogen bonds between the photoproduct and the halogen-bond donor 1,4-diiodoperchlorobenzene (C6I2Cl4). The observed topology in each solid is controlled by the regiochemical position of the halogen-bond accepting 4-pyridyl group. This paper demonstrates the ability to vary the topology of molecular networks by altering the position of the halogen bond acceptor within the cyclobutane-based node.

Novel Trifluoromethyl Pyrimidinone Compounds With Activity Against Mycobacterium tuberculosis

The identification and development of new anti-tubercular agents are a priority research area. We identified the trifluoromethyl pyrimidinone series of compounds in a whole-cell screen against Mycobacterium tuberculosis. Fifteen primary hits had minimum inhibitory concentrations (MICs) with good potency IC90 is the concentration at which M. tuberculosis growth is inhibited by 90% (IC90 < 5 μM). We conducted a structure–activity relationship investigation for this series. We designed and synthesized an additional 44 molecules and tested all analogs for activity against M. tuberculosis and cytotoxicity against the HepG2 cell line. Substitution at the 5-position of the pyrimidinone with a wide range of groups, including branched and straight chain alkyl and benzyl groups, resulted in active molecules. Trifluoromethyl was the preferred group at the 6-position, but phenyl and benzyl groups were tolerated. The 2-pyridyl group was required for activity; substitution on the 5-position of the pyridyl ring was tolerated but not on the 6-position. Active molecules from the series demonstrated low selectivity, with cytotoxicity against eukaryotic cells being an issue. However, there were active and non-cytotoxic molecules; the most promising molecule had an MIC (IC90) of 4.9 μM with no cytotoxicity (IC50 > 100 μM). The series was inactive against Gram-negative bacteria but showed good activity against Gram-positive bacteria and yeast. A representative molecule from this series showed rapid concentration-dependent bactericidal activity against replicating M. tuberculosis bacilli with ~4 log kill in <7 days. Overall the biological properties were promising, if cytotoxicity could be reduced. There is scope for further medicinal chemistry optimization to improve the properties without major change in structural features.