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The largely uncharted complexation chemistry of the veterinary polyether ionophores, monensic and salinomycinic acids (HL) with metal ions of type M4+ and the known antiproliferative potential of antibiotics has provoked our interest in exploring the coordination processes between MonH/SalH and ions of Ce4+. (1) Methods: Novel monensinate and salinomycinate cerium(IV)-based complexes were synthesized and structurally characterized by elemental analysis, a plethora of physicochemical methods, density functional theory, molecular dynamics, and biological assays. (2) Results: The formation of coordination species of a general composition [CeL2(OH)2] and [CeL(NO3)2(OH)], depending on reaction conditions, was proven both experimentally and theoretically. The metal(IV) complexes [CeL(NO3)2(OH)] possess promising cytotoxic activity against the human tumor uterine cervix (HeLa) cell line, being highly selective (non-tumor embryo Lep-3 vs. HeLa) compared to cisplatin, oxaliplatin, and epirubicin.

Efficient transport of pharmaceuticals to malignant cells in the human body often requires the application of drug-delivery systems (DDSs) consisting of several building blocks, each of them bearing a specific function. While nanoparticles are promising as potential carrier moieties, biomolecules may add to the efficient delivery by binding several drug molecules simultaneously. In this contribution, we apply a combination of atomistic molecular dynamics simulations and density functional theory calculations to characterize a multi-component DDS for the transport of the anthracycline antibiotic doxorubicin (DOX), comprising a gold nanoparticle (NP) and a drug-binding peptide (DBP) grafted on the NP surface. We have shown previously that the DDS can stabilize one DOX per DBP. However, by increasing the drug load to a 2 : 1 DOX : DBP ratio the two drug molecules compete for the available adsorption sites, which may cause spontaneous dissociation of one DOX molecule. We identify the chain length of the DBP as a limiting factor for the drug-loading capacity and provide important guidelines for further optimization of multi-component functionalized DDSs.

Funding Information: AI acknowledges the support of projects icp009 (ALKOOL) of PRACE-ICEI (grant agreement 800858) for awarding access to Piz Daint, at the Swiss National Supercomputing Centre (CSCS), Switzerland and BG05M2OP001–1.001–0004 (UNITe) of the Bulgarian Ministry of Education and Science. For further details on points raised in this article, please contact aivanova@chem.uni-sofia.bg. Funding Information: Acknowledgements. JAGH is supported by the Biocenter Finland, the Helsinki Institute of Life Sciences, and the Faculty of Pharmacy, University of Helsinki. Publisher Copyright: © 2021 The Authors This collection of contributions from the European Network on Understanding Gastrointestinal Absorption-related Processes (UNGAP) community assembly aims to provide information on some of the current and newer methods employed to study the behaviour of medicines. It is the product of interactions in the immediate pre-Covid period when UNGAP members were able to meet and set up workshops and to discuss progress across the disciplines. UNGAP activities are divided into work packages that cover special treatment populations, absorption processes in different regions of the gut, the development of advanced formulations and the integration of food and pharmaceutical scientists in the food-drug interface. This involves both new and established technical approaches in which we have attempted to define best practice and highlight areas where further research is needed. Over the last months we have been able to reflect on some of the key innovative approaches which we were tasked with mapping, including theoretical, in silico, in vitro, in vivo and ex vivo, preclinical and clinical approaches. This is the product of some of us in a snapshot of where UNGAP has travelled and what aspects of innovative technologies are important. It is not a comprehensive review of all methods used in research to study drug dissolution and absorption, but provides an ample panorama of current and advanced methods generally and potentially useful in this area. This collection starts from a consideration of advances in a priori approaches: an understanding of the molecular properties of the compound to predict biological characteristics relevant to absorption. The next four sections discuss a major activity in the UNGAP initiative, the pursuit of more representative conditions to study lumenal dissolution of drug formulations developed independently by academic teams. They are important because they illustrate examples of in vitro simulation systems that have begun to provide a useful understanding of formulation behaviour in the upper GI tract for industry. The Leuven team highlights the importance of the physiology of the digestive tract, as they describe the relevance of gastric and intestinal fluids on the behaviour of drugs along the tract. This provides the introduction to microdosing as an early tool to study drug disposition. Microdosing in oncology is starting to use gamma-emitting tracers, which provides a link through SPECT to the next section on nuclear medicine. The last two papers link the modelling approaches used by the pharmaceutical industry, in silico to Pop-PK linking to Darwich and Aarons, who provide discussion on pharmacometric modelling, completing the loop of molecule to man.

Computational modeling of the optical characteristics of organic molecules with potential for thermally activated delayed fluorescence (TADF) may assist markedly the development of more efficient emitting materials for organic light-emitting diodes. Recent theoretical studies in this area employ mostly methods from density functional theory (DFT). In order to obtain accurate predictions within this approach, the choice of a proper functional is crucial. In the current study, we focus on testing the performance of a set of DFT functionals for estimation of the excitation and emission energy and the excited singlet-triplet energy gap of three newly synthesized compounds with capacity for TADF. The emitters are designed specifically to enable charge transfer by π-electron conjugation, at the same time possessing high-energy excited triplet states. The functionals chosen for testing are from various groups ranging from gradient-corrected through global hybrids to range-separated ones. The results show that the monitored optical properties are especially sensitive to how the long-range part of the exchange energy is treated within the functional. The accurate functional should also be able to provide well balanced distribution of the π-electrons among the molecular fragments. Global hybrids with moderate (less than 0.4) share of exact exchange (B3LYP, PBE0) and the meta-GGA HSE06 are outlined as the best performing methods for the systems under study. They can predict all important optical parameters correctly, both qualitatively and quantitatively.

The saponin escin, extracted from horse chestnut seeds, forms adsorption layers with high viscoelasticity and low gas permeability. Upon deformation, escin adsorption layers often feature surface wrinkles with characteristic wavelength. In previous studies, we investigated the origin of this behavior and found that the substantial surface elasticity of escin layers may be related to a specific combination of short-, medium-, and long-range attractive forces, leading to tight molecular packing in the layers. In the current study, we performed atomistic molecular dynamics simulations of 441 escin molecules in a dense adsorption layer with an area per molecule of 0.49 nm2. We found that the surfactant molecules are less submerged in water and adopt a more upright position when compared to the characteristics determined in our previous simulations with much smaller molecular models. The number of neighbouring molecules and their local orientation, however, remain similar in the different-size models. To maintain their preferred mutual orientation, the escin molecules segregate into well-ordered domains and spontaneously form wrinkled layers. The same specific interactions (H-bonds, dipole–dipole attraction, and intermediate strong attraction) define the complex internal structure and the undulations of the layers. The analysis of the layer properties reveals a characteristic wrinkle wavelength related to the surface lateral dimensions, in qualitative agreement with the phenomenological description of thin elastic sheets.