Energy Of Complex Formation Research Articles

MHC2AffyPred: A machine-learning approach to estimate affinity of MHC class II peptides based on structural interaction fingerprints.

Understanding how MHC class II (MHC-II) binding peptides with differing lengths exhibit specific interaction at the core and extended sites within the large MHC-II pocket is a very important aspect of immunological research for designing peptides. Certain efforts were made to generate peptide conformations amenable for MHC-II binding and calculate the binding energy of such complex formation but not directed toward developing a relationship between the peptide conformation in MHC-II structures and the binding affinity (BA) (IC50 ). We present here a machine-learning approach to calculate the BA of the peptides within the MHC-II pocket for HLA-DRA1, HLA-DRB1, HLA-DP, and HLA-DQ allotypes. Instead of generating ensembles of peptide conformations conventionally, the biased mode of conformations was created by considering the peptides in the crystal structures of pMHC-II complexes as the templates, followed by site-directed peptide docking. The structural interaction fingerprints generated from such docked pMHC-II structures along with the Moran autocorrelation descriptors were trained using a random forest regressor specific to each MHC-II peptide lengths (9-19). The entire workflow is automated using Linux shell and Perl scripts to promote the utilization of MHC2AffyPred program to any characterized MHC-II allotypes and is made for free access at https://github.com/SiddhiJani/MHC2AffyPred. The MHC2AffyPred attained better performance (correlation coefficient [CC] of .612-.898) than MHCII3D (.03-.594) and NetMHCIIpan-3.2 (.289-.692) programs in the HLA-DRA1, HLA-DRB1 types. Similarly, the MHC2AffyPred program achieved CC between .91 and .98 for HLA-DP and HLA-DQ peptides (13-mer to 17-mer). Further, a case study on MHC-II binding 15-mer peptides of severe acute respiratory syndrome coronavirus-2 showed very close competency in computing the IC50 values compared to the sequence-based NetMHCIIpan v3.2 and v4.0 programs with a correlation of .998 and .570, respectively.

The crystal structure of the varicella-zoster Orf24-Orf27 nuclear egress complex spotlights multiple determinants of herpesvirus subfamily specificity

Varicella-zoster virus (VZV) is a human pathogen from the α-subfamily of herpesviruses. The VZV Orf24-Orf27 complex represents the essential viral core nuclear egress complex (NEC) that orchestrates the egress of the preassembled virus capsids from the nucleus. While previous studies have primarily emphasized that the architecture of core NEC complexes is highly conserved among herpesviruses, the present report focuses on subfamily-specific structural and functional features that help explain the differences in the autologous versus nonautologous interaction patterns observed for NEC formation across herpesviruses. Here, we describe the crystal structure of the Orf24-Orf27 complex at 2.1 Å resolution. Coimmunoprecipitation and confocal imaging data show that Orf24-Orf27 complex formation displays some promiscuity in a herpesvirus subfamily-restricted manner. At the same time, analysis of thermodynamic parameters of NEC formation of three prototypical α-, β-, and γ herpesviruses, i.e., VZV, human cytomegalovirus (HCMV), and Epstein–Barr virus (EBV), revealed highly similar binding affinities for the autologous interaction with specific differences in enthalpy and entropy. Computational alanine scanning, structural comparisons, and mutational data highlight intermolecular interactions shared among α-herpesviruses that are clearly distinct from those seen in β- and γ-herpesviruses, including a salt bridge formed between Orf24-Arg167 and Orf27-Asp126. This interaction is located outside of the hook-into-groove interface and contributes significantly to the free energy of complex formation. Combined, these data explain distinct properties of specificity and permissivity so far observed in herpesviral NEC interactions. These findings will prove valuable in attempting to target multiple herpesvirus core NECs with selective or broad-acting drug candidates.

Point defects and their impact on electrochemical performance in Na0.44MnO2 for sodium-ion battery cathode application.

Sodium manganese oxide Na0.44MnO2 (NMO) in an open structure with large tunnels is of great interest for sodium-ion battery cathode materials due to its high electrode voltage and capacity. However, its practical application is limited by poor rate performance, which can be tuned and improved by controlling point defects. We herein present a comprehensive study of intrinsic point defects in NMO using density functional theory (DFT) calculations in combination with thermodynamics. Using the DFT+U approach, we determine the formation energies of elementary defects and defect complexes depending on the sets of atomic chemical potentials, corresponding to a certain thermodynamic condition for the synthesis of stable NMO. Sodium interstitials are found to have the lowest formation energies in the relevant ranges of temperature and pressure. Other intrinsic point defects such as oxygen vacancies, sodium vacancies and manganese antisites can also be formed with proper formation energies and have an impact on the cathode performance. Compared to the perfect system, oxygen vacancies lower the electrode voltage, whereas manganese vacancies and antisites increase the voltage. We find that most point defects and defect complexes improve the sodium ion diffusivity, highlighting a proper control of defect formation for enhancing the performance of sodium-ion batteries.

Model-Based Design of Synthetic Antisense RNA for Predictable Gene Repression.

Our enhanced understanding of RNA folding and function has increased the use of small RNA regulators. Among these RNA regulators, synthetic antisense RNA (asRNA) is designed to contain an RNA sequence complementary to the target mRNA sequence, and the formation of double-stranded RNA (dsRNA) facilitates gene repression due to dsRNA degradation or prevention of ribosome access to the mRNA. Despite the simple complementarity rule, however, predictably tunable repression has been challenging when synthetic asRNAs are used. Here, the protocol for model-based asRNA design is described. This model can predict synthetic asRNA-mediated repression efficiency using two parameters: the change in free energy of complex formation (ΔGCF) and percent mismatch of the target binding region (TBR). The model has been experimentally validated in both Gram-positive and Gram-negative bacteria as well as for target genes in both plasmids and chromosomes. These asRNAs can be created by simply replacing the TBR sequence with one that is complementary to the target mRNA sequence of interest. In principle, this protocol can be applied to design and build asRNAs for predictable gene repression in various contexts, including multiple target genes and organisms, making asRNAs predictably tunable regulators for broad applications.

Silver(I)-Carbene Bond-Directed Rigidification-Induced Emissive Metallacage for Picric Acid Detection.

A new triphenylamine-based tetraimidazolium salt L was developed for silver(I)-carbene bond-directed synthesis of tetranuclear silver(I) octacarbene ([Ag4(L)2](PF6)4) metallacage 1. Interestingly, after assembly formation, metallacage 1 showed a nine-fold emission enhancement in dilute solution while ligand L was weakly fluorescent. This is attributed to the rigidity induced to the system by metal-carbene bond formation where the metal center acts as a rigidification unit. The enhanced emission intensity in dilute solution and the presence of the triphenylamine core made 1 a potential candidate for recognition of picric acid (PA). This recognition can be ascribed to the dual effect of ground-state charge-transfer complex formation and resonance energy transfer between the picrate and metallacage 1. For metallacage 1, a considerable detection limit toward PA was observed. The use of such metal-carbene bond-directed rigidification-induced enhanced emission for PA sensing is noteworthy.

Calculation of Energy for RNA/RNA and DNA/RNA Duplex Formation by Molecular Dynamics Simulation

The development of approaches for predictive calculation of hybridization properties of various nucleic acid (NA) derivatives is the basis for the rational design of the NA-based constructs. Modern advances in computer modeling methods provide the feasibility of these calculations. We have analyzed the possibility of calculating the energy of DNA/RNA and RNA/RNA duplex formation using representative sets of complexes (65 and 75 complexes, respectively). We used the classical molecular dynamics (MD) method, the MMPBSA or MMGBSA approaches to calculate the enthalpy (ΔH°) component, and the quasi-harmonic approximation (Q-Harm) or the normal mode analysis (NMA) methods to calculate the entropy (ΔS°) contribution to the Gibbs energy (Delta G_{{37}}^{^circ } ) of the NA complex formation. We have found that the MMGBSA method in the analysis of the MD trajectory of only the NA duplex and the empirical linear approximation allow calculation of the enthalpy of formation of the DNA, RNA, and hybrid duplexes of various lengths and GC content with an accuracy of 8.6%. Within each type of complex, the combination of rather efficient MMGBSA and Q-Harm approaches being applied to the trajectory of only the bimolecular complex makes it possible to calculate the Delta G_{{37}}^{^circ } of the duplex formation with an error value of 10%. The high accuracy of predictive calculation for different types of natural complexes (DNA/RNA, DNA/RNA, and RNA/RNA) indicates the possibility of extending the considered approach to analogs and derivatives of nucleic acids, which gives a fundamental opportunity in the future to perform rational design of new types of NA-targeted sequence-specific compounds.

Computer-Aided Design of Peptidomimetic Inhibitors of Falcipain-3: QSAR and Pharmacophore Models

In this work, antiparasitic peptidomimetics inhibitors (PEP) of falcipain-3 (FP3) of Plasmodium falciparum (Pf) are proposed using structure-based and computer-aided molecular design. Beginning with the crystal structure of PfFP3-K11017 complex (PDB ID: 3BWK), three-dimensional (3D) models of FP3-PEPx complexes with known activities ( IC50exp) were prepared by in situ modification, based on molecular mechanics and implicit solvation to compute Gibbs free energies (GFE) of inhibitor-FP3 complex formation. This resulted in a quantitative structure–activity relationships (QSAR) model based on a linear correlation between computed GFE (ΔΔGcom) and the experimentally measured IC50exp. Apart from the structure-based relationship, a ligand-based quantitative pharmacophore model (PH4) of novel PEP analogues where substitutions were directed by comparative analysis of the active site interactions was derived using the proposed bound conformations of the PEPx. This provided structural information useful for the design of virtual combinatorial libraries (VL), which was virtually screened based on the 3D-QSAR PH4. The end results were predictive inhibitory activities falling within the low nanomolar concentration range.

Solvatochromic Study of Two Carbanion Monosubstituted 4-Tolyl-1,2,4-triazol-1-ium Phenacylids in Binary Hydroxyl Solvent Mixtures

Two 4-tolyl-1,2,4-triazol-1-ium methylids, namely 4-tolyl-1,2,4-triazol-1-ium-phenacylid and 4-tolyl-1,2,4-triazol-1-ium-4′-nitro-phenacylid, are studied from solvatochromic point of view in binary solvent mixtures of water with ethanol and water with methanol. The contributions (expressed in percent) of the universal and specific interactions are separated from the spectral shifts recorded in the visible range for each composition of the binary solvent mixture. The essential role of the orientation and induction interactions in the studied solutions was demonstrated. Based on the statistic cell model of the binary solvent mixture solutions, the difference between the formation energies of ylid-water and ylid-alcohol complexes is estimated. The composition of the ylid’s first solvation shell was also established using the model of the binary solvent mixture solutions. The results obtained from the statistical cell model were compared with those obtained by using the Suppan’s model, resulting a good agreement.

A theoretical study of supramolecular aggregation of polydopamine tetramer subunits in aqueous solution

Conformational search for the most stable geometry connection of 16 sets of polydopamine (PDA) tetramer subunits has been systematically investigated using density functional theory (DFT) calculations. Our results indicated that the more planar subunits are, the more stable they are. This finding is in good agreement with recent experimental observations, which have suggested that PDA are composed of the nearly planar subunits that appear to be stacked together via the π–π interactions to form graphite-like layered aggregates associated with the balance of the intramolecular hydrogen bonds and steric effects from the indole and catechol moieties. Molecular dynamics (MD) simulations of 16 spherical clusters of the tetramer subunits of PDA in the gas and aqueous phase were performed at 298 K and confirmed the stability of supramolecular tetramer aggregates. The complex formation and binding energy of all 16 clusters are very strong although the shapes of the clusters in aqueous solution are not spherical and are very much different from those in the gas phase. The aggregations of all 16 clusters in aqueous solution were also confirmed from the profiles of the Kratky plot and the radius of gyration of all clusters. Our MD results in both gas phase and aqueous solution pointed out that there are high possibilities of aggregations of the 16 kinds of tetramer subunits although the conformations of each tetramer subunit are not flat. In summary, this work brings an insight into the controversial structure of PDA tetramer units and explains some of the important structural features found in the aqueous phase in comparison to the gas phase.

Structure determination of an amorphous drug through large-scale NMR predictions

Knowledge of the structure of amorphous solids can direct, for example, the optimization of pharmaceutical formulations, but atomic-level structure determination in amorphous molecular solids has so far not been possible. Solid-state nuclear magnetic resonance (NMR) is among the most popular methods to characterize amorphous materials, and molecular dynamics (MD) simulations can help describe the structure of disordered materials. However, directly relating MD to NMR experiments in molecular solids has been out of reach until now because of the large size of these simulations. Here, using a machine learning model of chemical shifts, we determine the atomic-level structure of the hydrated amorphous drug AZD5718 by combining dynamic nuclear polarization-enhanced solid-state NMR experiments with predicted chemical shifts for MD simulations of large systems. From these amorphous structures we then identify H-bonding motifs and relate them to local intermolecular complex formation energies.

Predicting the Adsorption of Amoxicillin and Ibuprofen on Chitosan and Graphene Oxide Materials: A Density Functional Theory Study.

The occurrence, persistence, and accumulation of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) represent a new environmental problem due to their harmful effects on human and aquatic life. A suitable absorbent for a particular type of pollutant does not necessarily absorb other types of compounds, so knowing the compatibility between a particular pollutant and a potential absorbent before experimentation seems to be fundamental. In this work, the molecular interactions between some pharmaceuticals (amoxicillin, ibuprofen, and tetracycline derivatives) with two potential absorbers, chitosan and graphene oxide models (pyrene, GO-1, and coronene, GO-2), were studied using the ωB97X-D/6-311G(2d,p) level of theory. The energetic interaction order found was amoxicillin/chitosan > amoxicillin/GO-1 > amoxicillin/GO-2 > ibuprofen/chitosan > ibuprofen/GO-2 > ibuprofen/GO-1, the negative sign for the interaction energy in all complex formations confirms good compatibility, while the size of Eint between 24–34 kcal/mol indicates physisorption processes. Moreover, the free energies of complex formation were negative, confirming the spontaneity of the processes. The larger interaction of amoxicillin Gos, compared to ibuprofen Gos, is consistent with previously reported experimental results, demonstrating the exceptional predictability of these methods. The second-order perturbation theory analysis shows that the amoxicillin complexes are mainly driven by hydrogen bonds, while van der Waals interactions with chitosan and hydrophobic interactions with graphene oxides are modelled for the ibuprofen complexes. Energy decomposition analysis (EDA) shows that electrostatic energy is a major contributor to the stabilization energy in all cases. The results obtained in this work promote the use of graphene oxides and chitosan as potential adsorbents for the removal of these emerging pollutants from water.

Calculation study on complex formation of catechins with β-cyclodextrin using density function theory

The inclusion of catechins with cyclodextrin (CD) is performed for the purpose of improving the water solubility and reducing the bitterness of catechins. In this study, the effect of catechins’ conformation on the formation of an inclusion complex between catechins and β-CD was examined by density functional theory (DFT) calculation at the B3PW91/cc-pVDZ level. It is known that the main components of catechins in tea leaves are (−)-epigallocatechin (EGC), which is a non-gallate-type catechin, and (−)-epigallocatechin gallate (EGCg), which is a gallate-type catechin. Catechins have a plurality of sites that can be included by β-CD (EGC: AC ring and B ring, EGCg: AC ring, B ring, and B′ ring). First, initial models for the calculation in which each ring of catechins gradually approaches into the cavity of β-CD were built. These initial models were optimized in water and then the optimized structure of the inclusion complex in water was determined. From the results of calculation, the degree of penetration of each ring into the β-CD cavity, the complex formation energy, and the number of intermolecular hydrogen bonds were examined. The results of calculation showed that the AC ring of catechins is most deeply included in the β-CD cavity and the B′ ring of catechins forms an energetically stable complex with β-CD. It was found that the inclusion complex of catechins and β-CD is stabilized energetically by intermolecular hydrogen bonds.

Effect of Oxygen-Donor Charge on Adjacent Nitrogen-Donor Interactions in Eu3+ Complexes of Mixed N,O-Donor Ligands Demonstrated on a 10-Fold [Eu(TPAMEN)]3+ Chelate Complex.

To reduce high-level radiotoxic waste generated by nuclear power plants, highly selective separation agents for minor actinides are mandatory. The mixed N,O-donor ligand N,N,N',N'-tetrakis[(6-carboxypyridin-2-yl)methyl]ethylenediamine (H4TPAEN; 1) has shown good performance as a masking agent in Am3+/Eu3+ separation studies. Adjustments on the pyridyl backbone to raise the hydrophilicity led to a decrease in selectivity and a decrease in M3+-Nam interactions. An enhanced basicity of the pyridyl N-donors was given as a cause. In this work, we examine whether a decrease in O-donor basicity can promote the M3+-Nam interactions. Therefore, we replace the deprotonated "charged" carboxylic acid groups of TPAEN4- by neutral amide groups and introduce N,N,N',N'-tetrakis[(6-N″,N''-diethylcarbamoylpyridin-2-yl)methyl]ethylenediamine (TPAMEN; 2) as a new ligand. TPAMEN was crystallized with Eu(OTf)3 and Eu(NO3)3·6H2O to form positively charged 1:1 [Eu(TPAMEN)]3+ complexes in the solid state. Alterations in the M-O/N bond distances are compared to [Eu(TPAEN)]- and investigated by DFT calculations to expose the differences in charge/energy density distributions at europium(III) and the donor functionalities of the TPAEN4- and TPAMEN. On the basis of estimations of the bond orders, atomic charges spin populations, and density of states in the Eu and potential Am and Cm complexes, the specific contributions of the donor-metal interaction are analyzed. The prediction of complex formation energy differences for the [M(TPAEN)]- and [M(TPAMEN)]3+ (M3+ = Eu3+, Am3+) complexes provide an outlook on the potential performance of TPAMEN in Am3+/Eu3+ separation.

Conformational analysis and molecular design of anthranilic acid derivatives as partial agonists of the Farnesoid X Receptor (FXR) with favorable predicted pharmacokinetic profiles

We report here virtual design of new anthranilic acid derivatives (AAD) identified as potent partial Farnesoid X recep-tor (FXR) agonists with favorable predicted pharmacokinetic profiles. By in situ modification of the crystal structure (PDB ID: 3OLF) of FXR complex with a benzimidazole-based partial agonistic ligand, 3D models of 17 FXR:AADx complexes with known observed activity (EC50exp) were prepared to establish a quantitative structure–activity (QSAR) model and linear correla-tion between relative Gibbs free energy (GFE) of receptor-ligand complex formation (Gcom) and EC50exp: pEC50exp = -0,1146 Gcom + 8,175 (#); R2 = 0.98. A 3D QSAR pharmacophore model (PH4) derived from the QSAR directed our effort to design novel AAD analogs. During the design, an initial virtual library of 94501 AAD was focused down to 33134 drug-like compounds and finally, PH4 screened to identify 100 promising compounds. Theoretical EC50 (EC50pre) values of all analogs compounds were predicted by means of equation (#) and their pharmacokinetics (ADME) profiles were computed. More than 12 putative AADs display EC50pre 300 times superior to that of the reported most active training set inhibitor AAD1.

Calculation of Energy for RNA/RNA and DNA/RNA Duplex Formation by Molecular Dynamics Simulation

The development of approaches for predictive calculation of hybridization properties of various nucleic acid (NA) derivatives is the basis for the rational design of the NA-based constructs. Modern advances in computer modeling methods provide the feasibility of these calculations. We have analyzed the possibility of calculating the energy of DNA/RNA and RNA/RNA duplex formation using representative sets of complexes (65 and 75 complexes, respectively). We used the classical molecular dynamics (MD) method, the MMPBSA or MMGBSA approaches to calculate the enthalpy (ΔH°) component, and the quasi-harmonic approximation (Q-Harm) or the normal mode analysis (NMA) methods to calculate the entropy (ΔS°) contribution to the Gibbs energy (ΔG°37) of the NA complex formation. We have found that the MMGBSA method in the analysis of the MD trajectory of only the NA duplex and the empirical linear approximation allow calculation of the enthalpy of formation of the DNA, RNA, and hybrid duplexes of various lengths and GC content with an accuracy of 8.6%. Within each type of complex, the combination of rather efficient MMGBSA and Q-Harm approaches being applied to the trajectory of only the bimolecular complex makes it possible to calculate the ΔG°37 of the duplex formation with an error value of 10%. The high accuracy of predictive calculation for different types of natural complexes (DNA/RNA, DNA/RNA, and RNA/RNA) indicates the possibility of extending the considered approach to analogs and derivatives of nucleic acids, which gives a fundamental opportunity in the future to perform rational design of new types of NA-targeted sequence-specific compounds.

Quantum-Chemical Simulation of the Structure of Charge-Transfer Complexes of 9,10-Phenanthrenequinone Nitro-Derivatives with Phenanthrene. Crystal and Molecular Structure of 1 : 1 Complex of 2,4,7-Trinitro-9,10-phenanthrenequinone with Phenanthrene

Data on the structure and properties of charge transfer complexes of nitro derivatives of 9,10-phenanthrenequinone (acceptor) with phenanthrene (donor) were obtained by quantum chemical calculations. The energies of complex formation, the average distances between donor and acceptor planes, and the total charge transfer amounts were calculated. 1,3,6-Trinitro-9,10-phenanthrenequinone was shown to be the strongest acceptor in the studied series. The crystal and molecular structure of the 1 : 1 complex of 2,4,7-trinitro-9,10-phenanthrenequinone with phenanthrene [C14H5N3O8·C14H10] was determined by X-ray structural analysis.

BeX2 induced C-H bond activation: A concise computational glance

The effect of BeX2 (X = H, F, Cl, Br and CN) on the C-H bond activation of some aldehyde, ketone and imine molecules were assessed theoretically by the B3LYP/6–311++G(d,p) method. The interaction of BeX2 derivatives with oxygen atom in aldehydes and ketones as well as with nitrogen atom in imine molecules was studied. The interaction of beryllium atom with the carbonyl or imine functional groups stabilizes the conjugated bases after deprotonation which promotes C-H bond dissociation in all sample molecules. The acidity enhancement strongly depends on the ability of X moiety for charge distribution so that, the maximum acidity increasing is obtained by Be(CN)2 molecule. After deprotonation, charge distribution by Be(CN)2 leads stability of the conjugated base and as a result, increases the acidity. ΔHform and ΔGform (Enthalpies and Gibbs free energies of complex formation with BeX2), ΔHacid and ΔGacid (Enthalpies and Gibbs free energies of deprotonation process in the absence and presence of BeX2) were used for evaluating of acidity as the main parameter for C-H bond activation. Using these strategies, it was found that the beryllium compounds specially Be(CN)2 leads to activate C-H bonds in variety molecules and it can be used as a promising suitable catalyst for C-H functionalization organic syntheses.

Room Temperature Gas-Phase Detection and Gibbs Energies of Water Amine Bimolecular Complex Formation.

We have detected the H2O·DMA and H2O·TMA (DMA, dimethylamine; TMA, trimethylamine) bimolecular complexes at room temperature in the gas phase using Fourier transform infrared spectroscopy. For both complexes, five vibrational bands associated with the H2O molecule are observed and assigned. Within a reduced dimensional local mode framework, we set up a six-dimensional model, including the three H2O vibrational modes and three of the six intermolecular modes, all described with internal curvilinear coordinates. The single points on the potential energy surface and Eckart corrected dipole moment surface are calculated with the CCSD(T)-F12a/cc-pVDZ-F12 method. Combining the measured and calculated transition intensities, we determine the Gibbs energy of complex formation of both complexes from each of the observed bands. The multiple determinations give similar Gibbs energies, for each complex, and increase the confidence in the combined experimental and theoretical approach, and improve the accuracy of the determined Gibbs energies. The average Gibbs energies of complex formation are found to be 5.0 ± 0.2 and 3.8 ± 0.2 kJ/mol for H2O·DMA and H2O·TMA, respectively. In addition to the experimental uncertainty, there is a potential error on the calculated intensities corresponding to 0.4 kJ/mol. However, the small spread among the four determinations suggests that this error is even less. The Gibbs energies of these complexes serve as accurate benchmarks for theoretical approaches that are prevalent in hydrogen bonding and nucleation studies.

Thermodynamics of antibiotics: natural cyclodextrin inclusion complex formation and covering of nano-metric calcite with these substances

Isothermal titration calorimetry (ITC) has been used to characterize inclusion complex formation of natural (α-, β-, γ-)cyclodextrins with antibiotics (ampicillin—sodium, penicillin G—sodium, streptomycin sulfate) in aqueous solutions. ITC measurements were taken at 298.15 K on Isothermal Titration Calorimeter Nano ITC. The experimental data were analyzed on the basis of the independent site model. Based on the experimental values of equilibrium constant (K) and enthalpy of complex formation (ΔH), the Gibbs energy of complex formation (ΔG) and the entropy of complex formation (ΔS) have been calculated. The analysis of the obtained inclusion complexes show that independently of the kind of cyclodextrin and antibiotics the obtained equilibrium constants are almost the same, but it is a difference between the changes in enthalpies of complex formation for the investigated systems. The stoichiometry of complexes formed both by ampicillin—sodium and by penicillin G—sodium with all the natural cyclodextrins is the same and equal to 1:1 and the complex formation is entropy driven. Three antibiotics (ampicillin—sodium, penicillin G—sodium and streptomycin sulfate) have been used further for covering of the monodisperse calcium carbonate nanoparticles obtained in the reactor (three-phase reaction) with rotating disks. Three series of experiments have been performed. First was connected with adsorption of the antibiotics on the surface on nano-calcite and two others with intercalation of the drugs into nano-metric CaCO3 structure (aggregates). An intercalation has been performed in two ways: one where the antibiotic was added to the reactor chamber at the beginning of the precipitation reaction and second where it was added just after the end of the reaction. Both pure CaCO3 nanoparticle and antibiotic-coated CaCO3 powders were deeply analyzed by the use of the thermogravimetric and the differential scanning calorimetry method. The performed investigations showed that all the antibiotics used can be both adsorbed and intercalated into the nano-metric CaCO3 obtained in the reactor with rotating disks. The different adsorption obtained by different antibiotics was caused by the different interaction between them and nano-calcite, caused by their different structure. The experimental data have allowed also for distinction between the antibiotics molecules present on calcite surface (adsorption) or antibiotics molecules intercalated into the nano-calcite structure. The conducted research shows that both approaches, i.e., formation of inclusion complexes with natural cyclodextrins and covering (adsorption and intercalation) of nano-metric CaCO3, can be successfully implemented for their pharmaceutical applications.

Optical Clearing of Human Skin Using Polyethylene Glycols

Molecular docking and quantum chemistry (PM6 and DFT/B3LYP) methods have been used to investigate the interaction of a number of biological tissue immersion clearing agents (PEG200, PEG300 and PEG400) with collagen mimetic peptides (GPH) 3 . Correlations between the rate (efficiency) of optical clearing and the energy of complex formation are established.