2-((E)-2-((E)-4-Chloro-5-(2-((E)-5-methoxy-3,3-dimethyl-1-(3-phenylpropyl)indolin-2-ylidene) ethylidene)-1,1-dimethyl-1,2,5,6-tetrahydropyridin-1-ium-3-yl)vinyl)-5-methoxy-3,3-dimethyl-1-(3-phenylpropyl)-3H-indol-1-ium

A heptamethine fluorophore, ERB-60, has been synthesized efficiently in four steps in a good yield. The structure of this fluorophore consists of an electron-donating group (methoxy), a hydrophobic moiety (phenylpropyl) with a rotatable bond, a quaternary ammonium fragment, and indolium rings at the terminal ends connected via polymethine chain. All these inherent chemical features fine-tuned the optical properties of the fluorophore. This compound was characterized by both 1H NMR, 13C NMR and mass spectra. The optical properties, including molar absorptivity, fluorescence, Stokes’s shift, and quantum yield, were measured in different solvents such as DMSO, DMF, MeCN, i-PrOH, MeOH, and H2O. The wavelengths of maximum absorbance of ERB-60 were found to be in the range of 745–770 nm based on the solvents used. In decreasing order, the maximum wavelength of absorbance of ERB-60 in the tested solvents was DMSO > DMF > i-PrOH > MeOH > MeCN > H2O while the decreasing order of the extinction coefficient was found to be MeCN > MeOH > DMSO > i-PrOH > H2O > DMF. ERB-60 was found to be more photostable than IR-786 iodide, a commercially available dye, and brighter than the FDA-approved dye, indocyanine green (ICG).

Anti-COVID-19 Sulfonamides: A DFT, docking and ADMET study

Background: The development of a specific curative drug or prophylactic and vaccine is the desire to cure the COVID-19. Sulfonamide and its derivatives are famous for their multifaceted antibiotic and antiviral activities against verities of a pathogen. Objective: To find new potential molecules for COVID-19 treatment, we have tested some sulfonamide molecules (including antiviral compounds) as SARS CoV-2 Mpro inhibitors. Materials and Methods: In this study, the Density Functional Theory (DFT) and the Docking study have been utilized for protein-small molecule affinity prediction. The SwissADME server was used for pharmacokinetics and drug-like likeness prediction, and the Pred-hERG server was employed for cardiotoxicity prediction. Results: In this study, sixteen sulfonamides have been investigated in silico, with a perspective to obtaining a potential anti-covid compound. The sulfonamides have been subjected to molecular docking with SARS CoV-2 Mpro, mainly responsible for viral infection and replication. We discover the molecular flexibility and charge distribution profoundly affect the binding of the compounds to the protein. Moderately flexible (six rotatable bond) and less polar (sufficient hydrophobic) sulfonamide are favorable for strong binding with the enzyme. Here, the bioavailability properties like adsorption, distribution, metabolism, excretion, pharmacokinetics, and potential toxicity of these compounds have also been checked. Conclusion: Low cardio-toxicity and high bioavailability make these sulfonamides a good anti- COVID-19 drug option. The sulfonamide 16 was found to be the best.

Generality of Correlation between Yield and Reduced Mass of Raw Materials in Organic Reactions

To validate a generality of the correlation between product yield and reduced mass of raw materials, the regression analysis of 129 reaction examples (55 as a sample size) including at least 66 types of reactions used in syntheses of natural products such as peptides and terpenes was conducted. It was possible to predict a yield of a variety of synthetic reactions for a synthesis of natural product with many aliphatic carbon chains by applying a reduced mass, adjusted with a molecular weight and the number of rotatable bond, to the regression equation. Moreover, it was found that the increase in yield due to a use of the adjusted reduced mass correlated with the harmonic mean of the molar heat capacity of raw materials and was expressed as a second-order approximation within the analysis range.<br>

Generality of Correlation between Yield and Reduced Mass of Raw Materials in Organic Reactions

To validate a generality of the correlation between product yield and reduced mass of raw materials, the regression analysis of 129 reaction examples (55 as a sample size) including at least 66 types of reactions used in syntheses of natural products such as peptides and terpenes was conducted. It was possible to predict a yield of a variety of synthetic reactions for a synthesis of natural product with many aliphatic carbon chains by applying a reduced mass, adjusted with a molecular weight and the number of rotatable bond, to the regression equation. Moreover, it was found that the increase in yield due to a use of the adjusted reduced mass correlated with the harmonic mean of the molar heat capacity of raw materials and was expressed as a second-order approximation within the analysis range.<br>

Conformational Investigations in Flexible Molecules Using Orientational NMR Constraints in Combination with 3J-Couplings and NOE Distances

The downscaling of NMR tensorial interactions, such as dipolar couplings, from tens of kilohertz to a few hertz in low-order media is the result of dynamics spanning several orders of magnitudes, including vibrational modes (~ns-fs), whole-molecule reorientation (~ns) and higher barrier internal conformational exchange (<ms). In this work, we propose to employ these dynamically averaged interactions to drive an “alignment-tensor-free” molecular dynamic simulation with orientation constraints (MDOC) in order to efficiently access the conformational space sampled by flexible small molecules such as natural products. Key to this approach is the application of tensorial pseudo-force restraints which simultaneously guide the overall reorientation and conformational fluctuations based on defined memory function over the running trajectory. With the molecular mechanics force-field, which includes bond polarization theory (BPT), and complemented with other available NMR parameters such as NOEs and scalar J-couplings, MDOC efficiently arrives at dynamic ensembles that reproduce the entire NMR dataset with exquisite accuracy and theoretically reveal the systems conformational space and equilibrium. The method as well as its potential towards configurational elucidation is presented on diastereomeric pairs of flexible molecules: a small 1,4-diketone 1 with a single rotatable bond as well as a 24-ring macrolide related to the natural product mandelalide A 2.

Implementation of PLS discriminant analysis to rank indirubin derivatives against decoys

Partial Least Squares Discriminant Analysis (PLS-DA) is employed to obtain novel combinations of energetic terms present in classical scoring functions, which exceed and compensates the “traditional” consensus scheme. These novel scoring functions were involved to rank the database of indirubin inhibitors of glycogen synthase kinase-3β and cyclin dependent kinase-2 decoys from Directory of Useful Decoys. The ability of docking-scoring algorithm to prioritize the actives is assessed by means of several metrics. The best classification function includes donor component of Chemgauss2, steric contribution from Chemgauss3 and rotatable bond term of ScreenScore and provide significant improvement of enrichment factor at 5% of database.