Predicting Complexation Thermodynamic Parameters of β-Cyclodextrin with Chiral Guests by Using Swarm Intelligence and Support Vector Machines

The Particle Swarm Optimization (PSO) and Support Vector Machines (SVMs) approaches are used for predicting the thermodynamic parameters for the 1:1 inclusion complexation of chiral guests with β-cyclodextrin. A PSO is adopted for descriptor selection in the quantitative structure-property relationships (QSPR) of a dataset of 74 chiral guests due to its simplicity, speed, and consistency. The modified PSO is then combined with SVMs for its good approximating properties, to generate a QSPR model with the selected features. Linear, polynomial, and Gaussian radial basis functions are used as kernels in SVMs. All models have demonstrated an impressive performance with R2 higher than 0.8

Molecular Dynamic Simulation Analysis on the Inclusion Complexation of Plumbagin with β-Cyclodextrin Derivatives in Aqueous Solution

Stable encapsulation of medically active compounds can lead to longer storage life and facilitate the slow-release mechanism. In this work, the dynamic and molecular interactions between plumbagin molecule with β-cyclodextrin (BCD) and its two derivatives, which are dimethyl-β-cyclodextrin (MBCD), and 2-O-monohydroxypropyl-β-cyclodextrin (HPBCD) were investigated. Molecular dynamics simulations (MD) with GLYCAM-06 and AMBER force fields were used to simulate the inclusion complex systems under storage temperature (4 °C) in an aqueous solution. The simulation results suggested that HPBCD is the best encapsulation agent to produce stable host–guest binding with plumbagin. Moreover, the observation of the plumbagin dynamic inside the binding cavity revealed that it tends to orient the methyl group toward the wider rim of HPBCD. Therefore, HPBCD is a decent candidate for the preservation of plumbagin with a promising longer storage life and presents the opportunity to facilitate the slow-release mechanism

Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations

The complexation of β-cyclodextrin (β-CD) with cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) was investigated using molecular docking and M062X/6-31G(d,p) calculations. The calculations suggested two possible complex formations of 1:1 and 2:1 host-guest molecular ratio of β-CD with CBD and THC. The preferred orientation of all complexes in this study exhibited the hydrogen bonding between hydroxy-substituted benzene ring of CBD and THC with the β-CD’s secondary hydroxy groups at the wide rim. The calculated complexation energies indicate that formation of the 2:1 complexes (−83.53 to −135.36 kcal/mol) was more energetically favorable and chemically stable than the 1:1 complexes (−30.00 to −34.92 kcal/mol). However, the deformation energies of the host and the guest components in the 2:1 complexes (37.47–96.91 kcal/mol) are much higher than those in the 1:1 complexes (3.49–8.69 kcal/mol), which means the formation processes of the 2:1 complexes are more difficult due to the rigidity of the dimeric β-CDs. Therefore, the inclusion complexes of β-CD with CBD and THC are more likely to be in 1:1 host-guest ratio than in 2:1 molecular ratio. The results of this study supported the experimental results that the complexation constant of 1:1 β-CD/CBD (Ks = 300 M−1) is greater than that of 2:1 β-CDs/CBD (Kss = 0.833 M−1). Altogether, this study introduced the fitting parameters that could indicate the stability of the molecular fits in complex formation of each stoichiometry host-guest ratio, which are important for the assessment of the inclusion mechanisms as well as the relationships of reactants and products in chemical reactions

Structural and Dynamics Perspectives on the Binding of Substrate and Inhibitors in Mycobacterium tuberculosis DHFR

Dihydrofolate reductase (DHFR), an essential enzyme in the folate pathway, is a potential target for new anti-tuberculosis drugs. Fifteen crystal structures of Mycobacterium tuberculosis DHFR complexed with NADPH and various inhibitors are available in the RCSB Protein Data Bank, but none of them is a substrate binding structure. Therefore, we performed molecular dynamics simulations on ternary complexes of M. tuberculosis DHFR:NADPH with a substrate (dihydrofolate) and each of three competitive inhibitors in 2,4-diaminopyrimidine series (P1, P157, and P169), in order to gain insight into the inhibition-mechanism of DHFR in the folate pathway. The binding energy and thermodynamics values of each system were calculated by the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) method. The dynamics of the enzyme and the motion of each amino acid residue at the active site were examined. The key factors that promote the binding of P157 and P169 on M. tuberculosis DHFR (mtbDHFR) reveal opportunities for using these compounds as novel anti-tuberculosis drugs

Molecular Dynamic Simulation Analysis on the Inclusion Complexation of Plumbagin with β-Cyclodextrin Derivatives in Aqueous Solution

Stable encapsulation of medically active compounds can lead to longer storage life and facilitate the slow-release mechanism. In this work, the dynamic and molecular interactions between plumbagin molecule with β-cyclodextrin (BCD) and its two derivatives, which are dimethyl-β-cyclodextrin (MBCD), and 2-O-monohydroxypropyl-β-cyclodextrin (HPBCD) were investigated. Molecular dynamics simulations (MD) with GLYCAM-06 and AMBER force fields were used to simulate the inclusion complex systems under storage temperature (4 °C) in an aqueous solution. The simulation results suggested that HPBCD is the best encapsulation agent to produce stable host–guest binding with plumbagin. Moreover, the observation of the plumbagin dynamic inside the binding cavity revealed that it tends to orient the methyl group toward the wider rim of HPBCD. Therefore, HPBCD is a decent candidate for the preservation of plumbagin with a promising longer storage life and presents the opportunity to facilitate the slow-release mechanism

Catalytic Activity Enhancement of Cu-Zn-Based Catalyst for Methanol Steam Reforming with Magnetic Inducement

Magnetic inducement was applied during metal loading to enhance Cu-Zn catalysts for methanol steam reforming in the temperature range of 200–300 °C. The supports used in this study were the γ-Al2O3 support and CeO2-Al2O3 supports prepared under different magnetic environments. Cu-Zn loading between the north and south poles (N-S) on the CeO2-Al2O3 support, prepared between two north poles (N-N), led to the highest H2 production at 300 °C (2796 ± 76 µmol/min), which is triple that of Cu-Zn/CeO2-Al2O3 prepared without magnetic inducement and ~11-fold the activity of the Cu-Zn/Al2O3 reference catalyst. The N-S magnetic environment during metal loading leads to lower reduction temperatures and larger Cu(1+):Cu(2+) ratio. These results showed that the pole arrangement of magnets during metal loading could affect the catalytic activity of the Cu-Zn catalyst owing to its influence on the reducibility and the oxidation state of Cu active metal

Theoretical Investigation of the Enantioselective Complexations between pfDHFR and Cycloguanil Derivatives

Point mutations in Plasmodium falciparum dihydrofolate reductase (pfDHFR), especially the double mutant variant (A16V + S108T), led to ineffective inhibiting by cycloguanil (Cyc). Cycloguanil derivatives showed good inhibiting properties against wild-type and mutant pfDHFR with an inhibition constant as low as the nanomolar level. However, there have been no reports on the stereochemistry of the compounds, and this is important because the pure enantiomeric form of a chiral drug can exert desirable, as well as non-desirable responses on the body or both. In this work, three-dimensional structures of Cyc derivatives in R and S configuration were constructed and optimized using Hartree-Fock/6-31G (d,p). Their structures were docked into the binding pocket of wild-type and double mutant (A16V + S108T) pfDHFR, complexed with nicotinamide adenine dinucleotide phosphate (NADPH). Results indicate that both wild-type and mutant pfDHFR are enantioselective towards enantiomeric Cyc derivatives (R and S configuration)