The design of molecular rotors that can rotate in ultrahigh speeds is important for the development of artificial molecular machines. Based on theoretical calculations, we demonstrate that two kinds of...

We carried out a computational investigation at the density functional theory (M06-2X) level on the effects of oriented external electric fields (OEEF) on activation barriers and stereochemical output of the thermal ring opening of 3-substituted cyclobutenes (C4H5X) to butadienes. It is well known that with πelectron-donor substituents (X = CH 3 , NH 2 ), the conrotatory outward rotation is preferred, while with π-electron-acceptor substituents (X = CHO, NO, BH 2 ), the conrotatory inward process becomes favored. In the presence of the OEEF applied along the three axes x, y, and z in either positive or negative direction, for both π-donor and π-acceptor substituents, we observed either catalysis or inhibition. Both effects were consistent with the change of the induced dipole along the direction of the applied field. An interesting effect was observed for X = CHO and NO. The simultaneous catalysis and inhibition of the outward and inward transformation leads to a reversed ratio between outward and inward transformation, with the former being favored (stereochemical inversion). Such effect was not observed for X = BH 2 (the strongest π-acceptor examined here). In this case, in the absence of the applied field, the difference between the inward and outward barriers is too large and the simultaneous catalysis and inhibition of the outward and inward transformation is not capable of determining the stereochemical inversion.

The electronic, optical, and redox properties of thiophene-based materials have made them pivotal in nanoscience and nanotechnology. However, the exploitation of oligothiophenes in photodynamic therapy is hindered by their intrinsic hydrophobicity that lowers their biocompatibility and availability in water environments. Here, we developed human serum albumin (HSA)–oligothiophene bioconjugates that afford the use of insoluble oligothiophenes in physiological environments. UV–vis and electrophoresis proved the conjugation of the oligothiophene sensitizers to the protein. The bioconjugate is water-soluble and biocompatible, does not have any “dark toxicity”, and preserves HSA in the physiological monomeric form, as confirmed by dynamic light scattering and circular dichroism measurements. In contrast, upon irradiation with ultralow light doses, the bioconjugate efficiently produces reactive oxygen species (ROS) and leads to the complete eradication of cancer cells. Real-time monitoring of the photokilling activity of the HSA–oligothiophene bioconjugate shows that living cells “explode” upon irradiation. Photodependent and dose-dependent apoptosis is one of the primary mechanisms of cell death activated by bioconjugate irradiation. The bioconjugate is a novel theranostic platform able to generate ROS intracellularly and provide imaging through the fluorescence of the oligothiophene. It is also a real-time self-reporting system able to monitor the apoptotic process. The induced phototoxicity is strongly confined to the irradiated region, showing localized killing of cancer cells by precise light activation of the bioconjugate.

The persistency of COVID-19 in the world and the continuous rise of its variants demand new treatments to complement vaccines. Computational chemistry can assist in the identification of moieties able to lead to new drugs to fight the disease. Fullerenes and carbon nanomaterials can interact with proteins and are considered promising antiviral agents. Here, we propose the possibility to repurpose fullerenes to clog the active site of the SARS-CoV-2 protease, Mpro. Through the use of docking, molecular dynamics, and energy decomposition techniques, it is shown that C60 has a substantial binding energy to the main protease of the SARS-CoV-2 virus, Mpro, higher than masitinib, a known inhibitor of the protein. Furthermore, we suggest the use of C70 as an innovative scaffold for the inhibition of SARS-CoV-2 Mpro. At odds with masitinib, both C60 and C70 interact more strongly with SARS-CoV-2 Mpro when different protonation states of the catalytic dyad are considered. The binding of fullerenes to Mpro is due to shape complementarity, i.e., vdW interactions, and is aspecific. As such, it is not sensitive to mutations that can eliminate or invert the charges of the amino acids composing the binding pocket. Fullerenic cages should therefore be more effective against the SARS-CoV-2 virus than the available inhibitors such as masinitib, where the electrostatic term plays a crucial role in the binding.

The terms and conditions for the reuse of this version of the manuscript are specified in the publishing policy. For all terms of use and more information see the publisher's website.