Cooperative and anticooperative effects in resonance assisted hydrogen bonds in merged structures of malondialdehyde

We analyzed non-additive effects in resonance assisted hydrogen bonds (RAHBs) in different b-enolones, which are archetypal compounds of these types of interactions. For this purpose, we used (i) potential energy curves to compute the formation energy, DERAHB form , of the RAHBs of interest in different circumstances along with (ii) tools offered by quantum chemical topology, namely, the Quantum Theory of Atoms In Molecules (QTAIM) and the Interacting Quantum Atoms (IQA) electronic energy partition. We established the effect that a given H-bond exerts over DERAHB form associated with another RAHB, determining in this way the cooperativity or the anticooperativity of these interactions. The mesomeric structures and the QTAIM delocalisation indices are consistent with the determined cooperative or anticooperative character of two given RAHBs. The HB cooperativity and anticooperativity studied herein are directly reflected in the IQA interaction energy EOH int , but they are modulated by the surrounding hydrocarbon chain. The IQA decomposition of DEcoop, a measure of the cooperativity between a pair of interacting RAHBs, indicates that the analyzed H-bond cooperative/anticooperative effects are associated with greater/smaller (i) strengthening of the pseudo-bicyclic structure of the compounds of interest and (ii) electron localisations with its corresponding changes in the intra and intermolecular exchange–correlation contributions to DERAHB form . Overall, we expect that this investigation will provide valuable insights into the interplay among hydrogen bonded atoms and the p system in RAHBs contributing in this way to the understanding of the general features of H-bonds.

Atoms in molecules in real space: a fertile field for chemical bonding

In this perspective, we review some recent advances in the concept of atoms-in-molecules from a real space perspective. We first introduce the general formalism of atomic weight factors that allows unifying the treatment of fuzzy and non-fuzzy decompositions under a common algebraic umbrella. We then show how the use of reduced density matrices and their cumulants allows partitioning any quantum mechanical observable into atomic or group contributions. This circumstance provides access to electron counting as well as energy partitioning, on the same footing. We focus on how the fluctuations of atomic populations, as measured by the statistical cumulants of the electron distribution functions, are related to general multi-center bonding descriptors. Then we turn our attention to the interacting quantum atom energy partitioning, which is briefly reviewed since several general accounts on it have already appeared in the literature. More attention is paid to recent applications to large systems. Finally, we consider how a common formalism to extract electron counts and energies can be used to establish an algebraic justification for the extensively used bond order-bond energy relationships. We also briefly review a path to recover one-electron functions from real space partitions. Although most of the applications considered will be restricted to real space atoms taken from the quantum theory of atoms in molecules, arguably the most successful of all the atomic partitions devised so far, all the take-home messages from this perspective are generalizable to any real space decompositionsWe acknowledge the spanish MICINN, grant PID2021-122763NB-I00 and the FICyT, grant IDI/2021/000054 for financial support. TRR gratefully acknowledges DGTIC/UNAM for computer time (LANCAD-UNAM-DGTIC 250

The multikinase inhibitor EC‐70124 synergistically increased the antitumor activity of doxorubicin in sarcomas

Cytotoxic drugs like doxorubicin remain as the most utilized agents in sarcoma treatment. However, advanced sarcomas are often resistant, thus stressing the need for new therapies aimed to overcome this resistance. Multikinase inhibitors provide an efficient way to target several pro-tumorigenic pathways using a single agent and may constitute a valuable strategy in the treatment of sarcomas, which frequently show an aberrant activation of pro-tumoral kinases. Therefore, we studied the antitumor activity of EC-70124, an indolocarbazole analog that have demonstrated a robust ability to inhibit a wide range of pro-survival kinases. Evaluation of the phospho-kinase profile in cell-of-origin sarcoma models and/or sarcoma primary cell lines evidenced that PI3K/AKT/mTOR, JAK/STAT or SRC were among the most highly activated pathways. In striking contrast with the structurally related drug midostaurin, EC-70124 efficiently prevented the phosphorylation of these targets and robustly inhibited proliferation through a mechanism associated to the induction of DNA damage, cell cycle arrest and apoptosis. In addition, EC-70124 was able to partially reduce tumor growth in vivo. Importantly, this compound inhibited the expression and activity of ABC efflux pumps involved in drug resistance. In line with this ability, we found that the combined treatment of EC-70124 with doxorubicin resulted in a synergistic cytotoxic effect in vitro and an increased antitumor activity of this cytotoxic drug in vivo. Altogether, these results uncover the capability of the novel multikinase inhibitor EC-70124 to counteract drug resistance in sarcoma and highlight its therapeutic potential when combined with current treatmentsPeer ReviewedPostprint (author's final draft

Density functional calculations of small anionic clusters of group III nitrides

In this paper, we study the changes in the structural, vibrational, bonding, and electronic properties of small clusters of the group III nitrides when an electron is added to the neutral clusters. The results, based on density functional calculations, reveal that the addition of an electron induces significant structural changes in the neutral cluster configurations. The atomic charge analysis suggests that the added electron is located over the metallic atoms in dimers and trimers and equally shared by metal and nitrogen atoms in monomers. The calculated electron affinity values depend on both the cations and the structural configuration in these clusters