Porous coatings to control release rates of essential oils to generate an atmosphere with botanical actives

Essential oils have been used in diverse areas such as packaging, agriculture and cosmetics, for their antimicrobial and pesticide activity. The organic volatile compounds of the essential oils are involved in its activity. Controlling their release helps to prolong their functionality. In this study, a functionalized calcium carbonate porous coating was employed to control the release of thyme and rosemary oil in a confined space. The release rate was evaluated at 7 °C and 23 °C, gravimetrically. It was shown that the capillary effect of the porous coating slowed down the release of the volatiles into the headspace compared to the bulk essential oil. A linear drive force model was used to fit the obtained data from both essential oils. The model showed that rosemary reached the asymptotic mass loss equilibrium faster than thyme. This result can be explained by the diverse composition and concentration of monoterpenoids between the two essential oils. Temperature and degree of loading also played important roles in the desorption of the essential oils. It was observed that at high degrees of loading and temperatures the desorption of essential oils was higher. The above-described technology could be used for applications related to food preservation, pest control among others

Localization of ligands within human carbonic anhydrase II using F-19 pseudocontact shift analysis

Unraveling the native structure of protein-ligand complexes in solution enables rational drug design. We report here the use of 19F pseudocontact shift (PCS) NMR as a method to determine fluorine positions of high affinity ligands bound within the drug target human carbonic anhydrase II with high accuracy. Three different ligands were localized within the protein by analysis of the obtained PCS from simple onedimensional 19F spectra with an accuracy of up to 0.8 degrees A. In order to validate the PCS, four to five independent magnetic susceptibility tensors induced by lanthanide chelating tags bound site-specifically to single cysteine mutants were refined. Least-squares minimization and a Monte-Carlo approach allowed the assessment of experimental errors on the intersection of the corresponding four to five PCS isosurfaces. By defining an angle score that reflects the relative isosurface orientation for different tensor combinations, it was established that the ligand can be localized accurately using only three tensors, if the isosurfaces are close to orthogonal. For two out of three ligands, the determined position closely matched the X-ray coordinates. Our results for the third ligand suggest, in accordance with previously reported ab initio calculations, a rotated position for the difluorophenyl substituent, enabling a favorable interaction with Phe-131. The lanthanide-fluorine distance varied between 22 and 38 degrees A and induced 19F PCS ranged from 0.078 to 0.409 ppm, averaging to 0.213 ppm. Accordingly, even longer metal-fluorine distances will lead to meaningful PCS, rendering the investigation of protein-ligand complexes significantly larger than 30 kDa feasible

Arylsulfonamides as Inhibitors for Carbonic Anhydrase : Prediction & Validation

Arylsulfonamide derivs. are widely studied high affinity inhibitors of the isoenzyme human carbonic anhydrase II (hCA II).  From mol. dynamics simulations and MM-GBSA calcns., reliable (R = 0.89) relative binding free energies are detd. for 17 previously exptl. characterized protein-ligand complexes.  Decompn. of these energies led to the identification of crit. amino acid residues with a significant contribution to the affinity towards the ligands.  In particular, Leu198 was predicted as a key residue and was subjected to computational mutagenesis.  This prediction was verified exptl. by producing hCA II mutants L198A, L198F and L198Q and detg. the resulting affinities towards inhibitor 1.  The computed vs. exptl. energies are in good agreement thus suggesting that the force field parameters reported herein are useful for the in silico design of a wider range of carbonic anhydrase inhibitors

Human Carbonic Anhydrase II as a host for piano-stool complexes bearing a sulfonamide anchor

d(6)-piano-stool complexes bearing an arylsulfonamide anchor display sub-micromolar affinity towards human Carbonic Anhydrase II (hCA II). The 1.3 Å resolution X-ray crystal structure of [(η(6)-C(6)Me(6))Ru(bispy 3)Cl](+)⊂ hCA II highlights the nature of the host-guest interactions

Scoring Multipole Electrostatics in Condensed-Phase Atomistic Simulations

Permanent multipoles (MTPs) embody a natural extension to common point-charge (PC) representations in atomistic simulations. In this work, we propose an alternative to the computationally expensive MTP molecular dynamics simulations by running a simple PC simulation and later reevaluate“score’’all energies using the more detailed MTP force field. The method, which relies on the assumption that the PC and MTP force fields generate closely related phase spaces, is accomplished by enforcing identical sets of monopoles between the two force fieldseffectively highlighting the higher MTP terms as a correction to the PC approximation. We first detail our consistent parametrization of the electrostatics and van der Waals interactions for the two force fields. We then validate the method by comparing the accuracy of protein–ligand binding free energies from both PC and MTP-scored representations with experimentally determined binding constants obtained by us. Specifically, we study the binding of several arylsulfonamide ligands to human carbonic anhydrase II. We find that both representations yield an accuracy of 1 kcal/mol with respect to experiment. Finally, we apply the method to rank the energetic contributions of individual atomic MTP coefficients for molecules solvated in water. All in all, MTP scoring is a computationally appealing method that can provide insight into the multipolar electrostatic interactions of condensed-phase systems

Scoring Multipole Electrostatics in Condensed-Phase Atomistic Simulations

Permanent multipoles (MTPs) embody a natural extension to common point-charge (PC) representations in atomistic simulations. In this work, we propose an alternative to the computationally expensive MTP molecular dynamics simulations by running a simple PC simulation and later reevaluate—“score’’—all energies using the more detailed MTP force field. The method, which relies on the assumption that the PC and MTP force fields generate closely related phase spaces, is accomplished by enforcing identical sets of monopoles between the two force fields—effectively highlighting the higher MTP terms as a correction to the PC approximation. We first detail our consistent parametrization of the electrostatics and van der Waals interactions for the two force fields. We then validate the method by comparing the accuracy of protein–ligand binding free energies from both PC and MTP-scored representations with experimentally determined binding constants obtained by us. Specifically, we study the binding of several arylsulfonamide ligands to human carbonic anhydrase II. We find that both representations yield an accuracy of 1 kcal/mol with respect to experiment. Finally, we apply the method to rank the energetic contributions of individual atomic MTP coefficients for molecules solvated in water. All in all, MTP scoring is a computationally appealing method that can provide insight into the multipolar electrostatic interactions of condensed-phase systems