TY - JOUR A1 - Shityakov, Sergey A1 - Sohajda, Tamás A1 - Puskas, Istaván A1 - Roewer, Norbert A1 - Förster, Carola A1 - Broscheit, Jens-Albert T1 - Ionization States, Cellular Toxicity and Molecular Modeling Studies of Midazolam Complexed with Trimethyl-β-Cyclodextrin JF - Molecules N2 - We investigated the ionization profiles for open-ring (OR) and closed-ring (CR) forms of midazolam and drug-binding modes with heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (trimethyl-β-cyclodextrin; TRIMEB) using molecular modeling techniques and quantum mechanics methods. The results indicated that the total net charges for different molecular forms of midazolam tend to be cationic for OR and neutral for CR at physiological pH levels. The thermodynamic calculations demonstrated that CR is less water-soluble than OR, mainly due to the maximal solvation energy (ΔG(CR)(solv = -9.98 kcal·mol ⁻¹), which has a minimal ΔG(OR)(solv) of -67.01 kcal·mol⁻¹. A cell viability assay did not detect any signs of TRIMEB and OR/CR-TRIMEB complex toxicity on the cEND cells after 24 h of incubation in either Dulbecco's Modified Eagles Medium or in heat-inactivated human serum. The molecular docking studies identified the more flexible OR form of midazolam as being a better binder to TRIMEB with the fluorophenyl ring introduced inside the amphiphilic cavity of the host molecule. The OR binding affinity was confirmed by a minimal Gibbs free energy of binding (ΔG(bind)) value of -5.57 ± 0.02 kcal·mol⁻¹, an equilibrium binding constant (K(b)) of 79.89 ± 2.706 μM, and a ligand efficiency index (LE(lig)) of -0.21 ± 0.001. Our current data suggest that in order to improve the clinical applications of midazolam via its complexation with trimethyl-β-cyclodextrin to increase drug's overall aqueous solubility, it is important to concern the different forms and ionization states of this anesthetic. All mean values are indicated with their standard deviations. KW - quantum mechanics KW - free energy of solvation KW - torsional energy KW - trimethyl-β-cyclodextrin KW - midazolam KW - transition state KW - molecular docking KW - Gibbs free energy of binding Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119186 VL - 19 IS - 10 ER - TY - JOUR A1 - Jahnke, Frank A1 - Gies, Christopher A1 - Aßmann, Marc A1 - Bayer, Manfred A1 - Leymann, H.A.M. A1 - Foerster, Alexander A1 - Wiersig, Jan A1 - Schneider, Christian A1 - Kamp, Martin A1 - Höfling, Sven T1 - Giant photon bunching, superradiant pulse emission and excitation trapping in quantum-dot nanolasers JF - Nature Communications N2 - Light is often characterized only by its classical properties, like intensity or coherence. When looking at its quantum properties, described by photon correlations, new information about the state of the matter generating the radiation can be revealed. In particular the difference between independent and entangled emitters, which is at the heart of quantum mechanics, can be made visible in the photon statistics of the emitted light. The well-studied phenomenon of superradiance occurs when quantum–mechanical correlations between the emitters are present. Notwithstanding, superradiance was previously demonstrated only in terms of classical light properties. Here, we provide the missing link between quantum correlations of the active material and photon correlations in the emitted radiation. We use the superradiance of quantum dots in a cavity-quantum electrodynamics laser to show a direct connection between superradiant pulse emission and distinctive changes in the photon correlation function. This directly demonstrates the importance of quantum–mechanical correlations and their transfer between carriers and photons in novel optoelectronic devices. KW - photon bunching KW - quantum mechanics KW - superradiant pulse emission Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166144 VL - 7 IS - 11540 ER - TY - JOUR A1 - Sawatzky, Edgar A1 - Drakopoulos, Antonios A1 - Rölz, Martin A1 - Sotriffer, Christoph A1 - Engels, Bernd A1 - Decker, Michael T1 - Experimental and theoretical investigations into the stability of cyclic aminals JF - Beilstein Journal of Organic Chemistry N2 - Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking. Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pK a values of the N-3 nitrogen atom. Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account. KW - quantum mechanics KW - hydrolysis KW - kinetics KW - molecular mechanics KW - natural products Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160976 VL - 12 ER -