Publications by authors named "Laura Orian"

Concerted proton electron transfer (CPET) and hydrogen atom transfer (HAT) are two important mechanisms in many fields of chemistry, which are characterized by the transfer of one proton and one electron. The distinction between these mechanisms may be challenging in several reactions; thus, different computational methods have been developed for this purpose. In this work, we present a computational strategy to distinguish the two mechanisms, rationalizing the factors controlling the reactivity in four different model reactions.

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Photoinduced radical addition fragmentation chain transfer (PET-RAFT) polymerization typically requires high light intensity (>5 mW/cm2), limiting energy efficiency and scalability. We demonstrate that adding a base to PET-RAFT systems drastically enhances the reactivity of acidic chain transfer agents (CTAs) with Zn-based photocatalysts (Zn porphyrin and Zn phthalocyanine). This approach enables complete polymerization under microwatt light intensity (0.

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Chalcogenide exchange reactions are an important class of bimolecular nucleophilic substitution reactions (S2) involving sulfur and selenium species as nucleophile, central atom, and/or leaving group, which are fundamental throughout redox biology and metabolism. While thiol-disulfide exchange reactions have been deeply investigated, those involving selenium are less understood, especially with regards to the polarised selenenyl sulfides RSe-SR'. This functional group, which is fundamental in the biochemistry of glutathione peroxidase and thioredoxin reductase enzymes, was recently incorporated in the molecular scaffold of a TrxR1 specific probe, "RX1".

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Aqueous ammonia has been examined as a new weak base for the synthesis of [Au(NHC)Cl] complexes, as well as for the activation of C-H, S-H, and N-H bonds. Its low cost and mild operational conditions (in air and using technical grade solvents) make it an attractive alternative for producing gold-NHC complexes. Synthetic pathways have been investigated , assessing the role of the deprotonation and metalation steps within the reaction mechanisms.

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Although global vaccination campaigns alleviated the SARS-CoV-2 pandemic in terms of morbidity and mortality, the ability of the virus to originate mutants may reduce the efficacy of vaccines, posing a serious risk of a renewed pandemic. There is therefore a need to develop small molecules capable of targeting conserved viral targets, such as the main protease (M). Here, a series of benzisoselenazolones and diselenides were tested for their ability to inhibit M; then the most potent compounds were measured for antiviral activity in vitro, and the mechanism of action was investigated.

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In 1973, two major discoveries changed the face of selenium chemistry: the identification of the first mammal selenoenzyme, glutathione peroxidase 1, and the discovery of the synthetic utility of the so-called selenoxide elimination. While the chemical mechanism behind the catalytic activity of glutathione peroxidases appears to be mostly unveiled, little is known about the mechanisms of other selenoproteins and, for some of them, even the function lies in the dark. In chemistry, the capacity of organoselenides of catalyzing hydrogen peroxide activation for the practical manipulation of organic functional groups has been largely explored, and some mechanistic details have been clearly elucidated.

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Olanzapine is an antipsychotic drug that has been reported to suppress ferroptosis, a recently discovered form of regulated cell death. In this work, the scavenging activity of olanzapine and some of its metabolites is investigated using state-of-the-art density functional theory calculations (level of theory: (SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)). Indeed, this reactivity is linked to the therapeutic activity of many antipsychotic drugs and ferroptosis inhibitors.

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Article Synopsis
  • The text discusses a method for creating heterobimetallic carbene complexes featuring gold(i) and platinum(ii) through a straightforward one-pot synthesis using common starting materials.
  • This method leverages the varying reactivities of different amines to connect the two metals, allowing for selective and sequential addition of metal components.
  • The resulting complexes were evaluated for their effectiveness as anticancer drugs and compared against similar gold(i) and palladium(ii) complexes.
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The retro-Cope elimination reaction between dimethylhydroxylamine (DMHA) and various cyclic alkynes has been quantum chemically explored using DFT at ZORA-BP86/TZ2P. The purpose of this study is to understand the role of the following three unique activation modes on the overall reactivity, that is (i) additional cycloalkyne predistortion fused cycles, (ii) exocyclic heteroatom substitution on the cycloalkyne, and (iii) endocyclic heteroatom substitution on the cycloalkyne. Trends in reactivity are analyzed and explained by using the activation strain model (ASM) of chemical reactivity.

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This study reports a combined approach to assess the antioxidant activity of Zuccagnia-type propolis. Fractions exhibiting the highest antioxidant activities evidenced by DPPH, a β-carotene bleaching and superoxide radical scavenging activity-non-enzymatic assays, were processed by LC-HRMS/MS to characterize the relevant chemical compounds. A computational protocol based on the DFT calculations was used to rationalize the main outcomes.

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Seleninic acids and their precursors are well-known oxygen-transfer agents that can catalyze several oxidations with HO as the final oxidant. Until very recently, the Se(iv) "peroxyseleninic" acid species has been considered the only plausible catalytic oxidant. Conversely, in 2020, the involvement of Se(vi) "peroxyselenonic" acid has been proposed for the selenium mediated epoxidation of alkenes.

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Already known molecules which exhibit good electrochemiluminescence (ECL) efficiencies and high photoluminescence quantum yields (PLQY) have been structurally modified in order to increase their performance. The followed strategy is to stiffen the structures to limit the rotational and vibrational freedom degrees and favour radiative decay processes once excited. Molecules under investigation consist of donor-acceptor systems in which the acceptor fraction is a benzonitrile with an imidazole in para position, while the donor fraction consists of four diphenylamine (NPh) or 3,6-di(tert-butyl)-9H-carbazole (Cz) groups in the remaining positions on the central benzene ring.

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Notable thermal shifts in diselenides have been documented in Se NMR for more than 50 years, but no satisfactory explanation has been found. Here, five hypotheses are considered as possible explanations for the large temperature dependence of the Se chemical shifts of diaryl and dialkyl diselenides compared to monoselenides and selenols. Density functional theory calculations are provided to bolster hypotheses and better understand the effects of barrier height and dipole energies.

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The reactivity of Zn tetrahedral complexes with HO was investigated in silico, as a first step in their disruption process. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i. e.

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The clinical success of [Ra]RaCl (Xofigo®) for the palliative treatment of bone metastases in patients with prostate cancer has highlighted the therapeutic potential of α-particle emission. Expanding the applicability of radium-223 in Targeted Alpha Therapy of non-osseous tumors is followed up with significant interest, as it holds the potential to unveil novel treatment options in the comprehensive management of cancer. Moreover, the use of barium radionuclides, like barium-131 and -135m, is still unfamiliar in nuclear medicine applications, although they can be considered as radium-223 surrogates for imaging purposes.

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In continuation of our previous works on the cytotoxic properties of organopalladium compounds, in this contribution we describe the first systematic study of the anticancer activity of Pd(II)-aryl complexes. To this end, we have prepared and thoroughly characterized a wide range of palladium derivatives bearing different diphosphine, aryl and halide ligands, developing, when necessary, specific synthetic protocols. Most of the synthesized compounds showed remarkable cytotoxicity towards ovarian and breast cancer cell lines, with IC values often comparable to or lower than that of cisplatin.

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A series of macrocyclic ligands were considered for the chelation of Pb: 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetrazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetrazacyclotetradecane (TE4S). The equilibrium, the acid-mediated dissociation kinetics, and the structural properties of the Pb complexes formed by these chelators were examined by UV-Visible and nuclear magnetic resonance (NMR) spectroscopies, combined with potentiometry and density functional theory (DFT) calculations. The obtained results indicated that DO4S, DO3S, DO3SAm, and DO2A2S were able to efficiently chelate Pb and that the most suitable macrocyclic scaffold for Pb is 1,4,7,10-tetrazacyclododecane.

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PhSeZnCl, which is also known as Santi's reagent, can catalyze the reduction of hydrogen peroxide by thiols with a GPx-like mechanism. In this work, the first step of this catalytic cycle, i.e.

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Silver-111 is an attractive unconventional candidate for targeted cancer therapy as well as for single photon emission computed tomography and can be complemented by silver-103 for positron emission tomography noninvasive diagnostic procedures. However, the shortage of chelating agents capable of forming stable complexes tethered to tumor-seeking vectors has hindered their application so far. In this study, a comparative investigation of a series of sulfur-containing structural homologues, namely, 1,4,7-tris[2-(methylsulfanyl)ethyl)]-1,4,7-triazacyclononane (NO3S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetraazacyclotetradecane (TE4S) was conducted to appraise the influence of different polyazamacrocyclic backbones on Ag complexation.

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We set up an in silico experiment and designed a chimeric compound integrating molecular features from different efficient ROS (Reactive Oxygen Species) scavengers, with the purpose of investigating potential relationships between molecular structure and antioxidant activity. Furthermore, a selenium centre was inserted due to its known capacity to reduce hydroperoxides, acting as a molecular mimic of glutathione peroxidase; finally, since this organoselenide is a precursor of a N-heterocyclic carbene ligand, its Au(I) carbene complex was designed and examined. A validated protocol based on DFT (Density Functional Theory) was employed to investigate the radical scavenging activity of available sites on the organoselenide precursor ((SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)), as well as on the organometallic complex ((SMD)-M06-2X/SDD (Au), 6-311+G(d,p)//ZORA-BLYP-D3(BJ)/TZ2P), considering HAT (Hydrogen Atom Transfer) and RAF (Radical Adduct Formation) regarding five different radicals.

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Sulfoxides and selenoxides oxidize thiols to disulfides while being reduced back to sulfides and selenides. While the reduction mechanism of sulfoxides to sulfides has been thoroughly explored experimentally as well as computationally, less attention has been devoted to the heavier selenoxides. In this work, we explore the reductive mechanism of dimethyl selenoxide, as an archetypal selenoxide and, for the sake of comparison, the reductive mechanism of dimethyl sulfoxide to gain insight into the role of the chalcogen on the reaction substrate.

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The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. The main protease of SARS-CoV-2 (M) and the papain-like protease (PL) are essential for viral replication and are key targets for therapeutic development. In this work, we investigate the mechanisms of SARS-CoV-2 inhibition by diphenyl diselenide (PhSe) which is an archetypal model of diselenides and a renowned potential therapeutic agent.

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The reactive oxygen species (ROS) scavenging capacities of ginkgolides and bilobalide, which are the peculiar constituents of the extract of , are investigated in silico (level of theory: (SMD)-M06-2X/6-311+G(d,p)//M06-2X/6-31G(d)). Unlike other popular antioxidant natural substances, the carbon backbones of these compounds are entirely aliphatic and exclusively single C-C bonds are present. The selectivity for alkoxyl radicals via hydrogen-atom transfer (HAT) is assessed; importantly, the scavenging of peroxyl radicals is also possible from a peculiar site, here labeled C10 both for ginkgolides and bilobalide.

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Acid Sphingomyelinase (ASM) is a human phosphodiesterase that catalyzes the metabolism of sphingomyelin (SM) to ceramide and phosphocholine. ASM is involved in the plasma membrane cell repair and is associated with the lysosomal inner lipid membrane by nonbonding interactions. The disruption of those interaction would result in ASM release into the lysosomal lumen and consequent degradation of its structure.

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