Synthesis and photophysical properties of covalently liked boron dipyrromethene dyads

Two covalently linked boron dipyrromethene (BODIPY) dyads containing meso-phenyl BODIPY and meso-furyl BODIPY units connected via meso-meso and meso-α positions were synthesized by a Pd(0) coupling reaction. The dyads are freely soluble in common organic solvents and their structures were confirmed by HR-MS, 1D and 2D NMR techniques. Absorption studies indicate that the meso-aryl BODIPY and the meso-furyl BODIPY absorb in two different regions and that the meso-furyl BODIPY absorbs at lower energy compared to the meso-aryl BODIPY. The steady state fluorescence studies carried out by exciting the meso-aryl BODIPY unit clearly indicated an efficient singlet–singlet energy transfer from the meso-aryl BODIPY unit to meso-furyl BODIPY unit in both dyads. Furthermore the meso-α linked BODIPY dyad (φf = 0.41) is more fluorescent than its corresponding BODIPY monomers whereas the meso-meso linked BODIPY dyad (φf = 0.017) is weakly fluorescent. This unexpected observation was tentatively attributed to the restricted rotation of the BODIPY units in the meso-α linked dyad resulting in enhancement of radiative transitions. The time-resolved fluorescence study also indicated that meso-α linked BODIPY dyad is more fluorescent with singlet state lifetime of 3.7 ns. The DFT studies carried out on dyads are in agreement with the experimental observations

Application of the “EigenValue Analysis (EVANS)” Methodology to Build Quantitative Structure Pharmacokinetic Relationship Models

We present EigenValue ANalySis (EVANS), a QSPR methodology that considers 3D molecular information of enantiomeric ensembles of chiral molecules without the need to perform an alignment step. EVANS follows an intricate molecular modelling protocol that generates orthogonal eigenvalues from hybrid matrices of physicochemical properties and 3D structure; these eigenvalues are used as independent variables in QSPR analyses. The EVANS formalism has been presented and deployed to build quantitative structure pharmacokinetic relationship (QSPKR) models on a benchmark dataset for three critical PK parameters: steady-state volume of distribution (VDss), clearance (CL), and half-life (t1/2). Predictive QSPKR models were built by using the eigenvalues generated via the EVANS methodology in conjunction with multiple linear regression (MLR), random forest (RF), and support vector machine (SVM) algorithms, and it was observed that the EVANS QSPKR models sync with published work in the literature. Thus, we present the EVANS methodology as a first-line prediction tool to prioritise compounds in drug discovery and development

Synthesis and electronic properties of meso-furyl boron dipyrromethenes

Four meso-furyl boron-dipyrromethenes (BODIPYs) were synthesized and characterized. The X-ray structures solved for three meso-furyl BODIPYs indicated the presence of an intramolecular hydrogen bond between meso-furyl ‘O’ and ‘H’ of boron-dipyrromethene core resulting in decrease of dihedral angle between the meso-furyl group and boron-dipyrromethene core leading to better electronic interaction. However, the hydrogen bonding is absent in solution as confirmed by NMR studies in different solvents. The presence of meso-furyl group alters the electronic properties of BODIPY which reflected in the downfield shifts in 1H NMR, bathochromic shifts in absorption and emission bands compared to the meso-tolyl BODIPY. The electrochemical studies indicated that the meso-furyl BODIPYs are easier to reduce compared to meso-tolyl BODIPYs. DFT studies showed that the HOMO-LUMO energy gap is decreased in meso-furyl BODIPYs compared to meso-tolyl BODIPY which is in agreement with the experimental observations

Quantifying ligand–receptor interactions for gorge-spanning acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease

<div><p>There is a need for continued development of acetylcholinesterase (AChE) inhibitors that could prolong the life of acetylcholine in the synaptic cleft and also prevent the aggregation of amyloid peptides associated with Alzheimer’s disease. The lack of a 3D-QSAR model which specifically deconvulates the type of interactions and quantifies them in terms of energies has motivated us to report a CoRIA model vis-à-vis the standard 3D-QSAR methods, CoMFA and CoMSIA. The CoRIA model was found to be statistically superior to the CoMFA and CoMSIA models and it could efficiently extract key residues involved in ligand recognition and binding to AChE. These interactions were quantified to gauge the magnitude of their contribution to the biological activity. In order to validate the CoRIA model, a pharmacophore map was first constructed and then used to virtually screen public databases, from which novel scaffolds were cherry picked that were not present in the training set. The biological activities of these novel molecules were then predicted by the CoRIA, CoMFA, and CoMSIA models. The hits identified were purchased and their biological activities were measured by the Ellman’s method for AChE inhibition. The predicted activities are in unison with the experimentally measured biological activities.</p></div