Lily Arrué

The exceptional response of the gold nanocluster Au ₂₂ (Lys-Cys-Lys) ₁₆ , capable of generating reactive oxygen species (ROS) via electron transfer, was studied from both computational modeling and experimental characterization. An electron density perspective on remarkable features of gold nanoclusters and their photophysical applications provides a comprehensive study of the mechanism the gold nanocluster Au ₂₂ (Lys-Cys-Lys) ₁₆ undergoes as a type I photosensitizer. By means of molecular dynamics simulations, density functional theory for ground state and excited states, and linear response - time dependent density functional theory calculations, the optical properties of the nanocluster and its interactions in aqueous media were studied. Analysis of frontier molecular orbitals of Au ₂₂ (Lys-Cys-Lys) ₁₆ revealed that this nanocluster can transfer an electron from the gold core to a dioxygen molecule in the vicinity, generating ROS by following a spin-flip transition. The results suggest a strong connection between redistribution of electron density in the excited state and the ability of Au ₂₂ (Lys-Cys-Lys) ₁₆ to act as an electron donor rather than as a more commonly studied energy transfer mechanism for gold nanoclusters, mainly reported as photosensitizers type II. This study also probes the underlying mechanism of fluorescence quenching in aqueous media providing a comprehensive description of the experimental detection of ROS at different pH.

Neurodegenerative diseases (NDD) have been of great interest to scientists for a long time due to their multifactorial character. Among these pathologies, Alzheimer’s disease (AD) is of special relevance, and despite the existence of approved drugs for its treatment, there is still no efficient pharmacological therapy to stop, slow, or repair neurodegeneration. Existing drugs have certain disadvantages, such as lack of efficacy and side effects. Therefore, there is a real need to discover new drugs that can deal with this problem. However, as AD is multifactorial in nature with so many physiological pathways involved, the most effective approach to modulate more than one of them in a relevant manner and without undesirable consequences is through polypharmacology. In this field, there has been significant progress in recent years in terms of pharmacoinformatics tools that allow the discovery of bioactive molecules with polypharmacological profiles without the need to spend a long time and excessive resources on complex experimental designs, making the drug design and development pipeline more efficient. In this review, we present from different perspectives how pharmacoinformatics tools can be useful when drug design programs are designed to tackle complex diseases such as AD, highlighting essential concepts, showing the relevance of artificial intelligence and new trends, as well as different databases and software with their main results, emphasizing the importance of coupling wet and dry approaches in drug design and development processes.

Interaction between the BH₂⁺ and noble gases have been evaluated. Results show that BH₂Ng⁺ and BH₂Ng₂⁺ compounds (Ng = Ar–Rn) are thermodynamic and kinetically stable. Additionally, it is shown that these compounds form strong covalent B–Ng bonds.

Plants synthesize a large number of natural products, many of which are bioactive and have practical values as well as commercial potential. To explore this vast structural diversity, we present PSC-db, a unique plant metabolite database aimed to categorize the diverse phytochemical space by providing 3D-structural information along with physicochemical and pharmaceutical properties of the most relevant natural products. PSC-db may be utilized, for example, in qualitative estimation of biological activities (Quantitative Structure-Activity Relationship, QSAR) or massive docking campaigns to identify new bioactive compounds, as well as potential binding sites in target proteins. PSC-db has been implemented using the open-source PostgreSQL database platform where all compounds with their complementary and calculated information (classification, redundant names, unique IDs, physicochemical properties, etc.) were hierarchically organized. The source organism for each compound, as well as its biological activities against protein targets, cell lines and different organism were also included. PSC-db is freely available for public use and is hosted at the Universidad de Talca.

Despite the belief that noble gases (Ng) are completely inert and cannot form stable molecules, a variety of Ng compounds have been reported under laboratory conditions and others were recently detected in the interstellar media, raising interest in knowing and studying their bond nature and the physicochemical properties associated with their stability. In the present work, a systematic analysis of the thermodynamic stability of noble gas halide cations (NgX⁺) at the CCSD(T)/def2‐QZVP level have been performed. In addition, chemical bond was characterized through Natural Bonding Theory (NBO), Quantum Theory of Atoms in Molecules (QTAIM) and Energy Decomposition Analysis (EDA) with relativistic corrections. All methods suggest that NgX⁺ compounds possess a strong covalent bond. However, results show that only compounds containing Ar–Rn atoms are thermodynamic stable with a highly energetic and endergonic dissociation process. For these reasons, it is possible to suggest that several compounds that have not yet been reported could be obtained at the laboratory level or observed in the interstellar medium.

Alzheimer's disease is one of the pathologies that causes the most damage in the adult group, arising the need for more efficient drugs with less side effects. It demands the design of multitarget drugs against AD. In the present work, a computational study of five targets involved in Alzheimer's disease: AChE, BChE, BACE1, GSK-3 and CB2 is performed. Binding sites of these five