Investigating the role of Acanthamoeba polyphaga in protecting Human Adenovirus from water disinfection treatment

Human adenoviruses are responsible for a wide range of clinical infections and are present in aquatic environments, includingriver, seawater, drinking-water and sewage. Free-living amoebae (Acanthamoeba) in the same environments may internalizethem and other microorganisms can act as a reservoir for the internalized viruses. In this study, we studied the interactionbetween Acanthamoeba polyphaga and Human Adenovirus type 5 (HAdV 5) to determine whether the amoeba played a rolein protecting the internalized viruses from chemical disinfection. The efficacy of sodium hypochlorite disinfection against A.polyphaga and HAdV 5 either singly or in combination was assessed at three different concentrations. Individually, the amoebawere more resistant to chemical disinfection than HAdV 5 and remained alive after exposure to 5 mg/l of sodium hypochlorite.In contrast, HAdV 5 lost infectivity following exposure to 2.5 mg/l of sodium hypochlorite. When the amoeba and HAdV 5were co-cultured, infectious virus was found in the cytoplasm of the amoeba at 5 mg/l disinfectant concentration. These findingssuggest that the A. polyphaga is providing protection for the HAdV 5

Oxidative N-Heterocyclic Carbene Catalysis

N-Heterocyclic carbene (NHC) catalysis is a by now consolidated organocatalytic platform for a number of synthetic (asymmetric) transformations via diverse reaction modes/intermediates. In addition to the typical umpolung processes involving acyl anion/homoenolate equivalent species, implementation of protocols under oxidative conditions greatly expands the possibilities of this methodology. Oxidative NHC-catalysis allows for oxidative and oxygenative transformations through specific manipulations of Breslow-type species depending upon the oxidant used (external oxidant or O2/air), the derived NHC-bound intermediates paving the way to non-umpolung processes through activation of carbon atoms and heteroatoms. This review is intended to update the state of the art in oxidative NHC-catalyzed reactions that appeared in the literature from 2014 to present, with a strong focus to crucial intermediates and their mechanistic implications

Heterogenised catalysts for the H-transfer reduction reaction of aldehydes: influence of solvent and solvation effects on reaction performances

Heterogenisation of homogeneous catalysts onto solid supports represents a potential strategy to make the homogeneous catalytic function recyclable and reuseable. Yet, it is usually the case that immobilised catalysts have much lower catalytic activity than their homogeneous counterpart. In addition, the presence of a solid interface introduces a higher degree of complexity by modulating solid/fluid interactions, which can often influence adsorption properties of solvents and reactive species and, ultimately, catalytic activity. In this work, the influence of support and solvent in the H-transfer reduction of propionaldehyde over Al((OPr)-Pr-i)(3)-SiO2, Al((OPr)-Pr-i)(3)-TiO2 and Al((OPr)-Pr-i)(3)-Al2O3 heterogenised catalysts has been studied. Reaction studies are coupled with both NMR relaxation measurements as well as molecular dynamics (MD) simulations in order to unravel surface and solvation effects during the reaction. The results show that, whilst the choice of the support does not influence significantly catalytic activity, reactions carried out in solvents with high affinity for the catalyst surface, or able to hinder access to active sites due to solvation effects, have a lower activity. MD calculations provide key insights into bulk solvation effects involved in such reactions, which are thought to play an important role in determining the catalytic behaviour. The activity of the heterogenised catalysts was found to be comparable with that of the homogeneous Al((OPr)-Pr-i)(3) catalysts for all supports used, showing that for the type of reaction studied immobilisation of the homogeneous catalyst onto solid supports is a viable, robust and effective strategy

Humin Formation on SBA-15-pr-SO3H Catalysts during the Alcoholysis of Furfuryl Alcohol to Ethyl Levulinate: Effect of Pore Size on Catalyst Stability, Transport, and Adsorption

Herein, the alcoholysis of furfuryl alcohol in a series of SBA-15-pr-SO3H catalysts with different pore sizes is reported. Elemental analysis and NMR relaxation/diffusion methods show that changes in pore size have a significant effect on catalyst activity and durability. In particular, the decrease in catalyst activity after catalyst reuse is mainly due to carbonaceous deposition, whereas leaching of sulfonic acid groups is not significant. This effect is more pronounced in the largest-pore-size catalyst C3, which rapidly deactivates after one reaction cycle, whereas catalysts with a relatively medium and small average pore size (named, respectively, C2 and C1) deactivate after two reaction cycles and to a lesser extent. CHNS elemental analysis showed that C1 and C3 experience a similar amount of carbonaceous deposition, suggesting that the increased reusability of the small-pore-size catalyst can be attributed to the presence of SO3H groups mostly present on the external surface, as corroborated by results on pore clogging obtained by NMR relaxation measurements. The increased reusability of the C2 catalyst is attributed to a lower amount of humin being formed and, at the same time, reduced pore clogging, which helps to maintain accessible the internal pore space

Humoral immunity induced by mRNA COVID-19 vaccines in Nursing Home Residents previously infected with SARS-CoV-2

Background: Nursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population. Aims: The present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection. Methods: We measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated. Results: Superior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time. Discussion: In a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity. Conclusions: These findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population

Organo- and bio-catalytic approaches to the synthesis of biologically relevant compounds by the Umpolung strategy

The design of new reactions for carbon-carbon bond formation is certainly the main field in which the efforts of organic chemists have been focused in the last forty years. In addition, the undoubted benefit brought by catalysis has made possible the exploration of new and previously unknown reactivities, which have paved the way for the synthesis of complex molecules in a more efficient manner. In this regard, our group has been involved for years in the investigation of the reversal reactivity of substrate molecules (umpolung), and during my period as Ph.D. student the activity has been mostly devoted to the exploration of this type of reactivity through two main catalytic approaches, namely organocatalysis and biocatalysis. The organocatalytic strategy was successfully employed in the synthesis of imidazoline-2-thiones via a domino process, which was characterized by the formation of a new carbon-carbon bond through an aza-benzoin reaction promoted by a N-Heterocyclic Carbene (NHC) catalyst. Afterwards, a new protocol was developed for the chemo- and enantioselective dearomatization of activated pyridinium salts through the NHC-catalyzed nucleophilic addition of umpoled aldehydes. Finally, the last work based on an organocatalytic approach dealt with the desymmetrization of 1,4-dihydropyridines by chiral NHC-oxidative catalysis. In the context of biocatalysis, the synthetic potential of the enzyme/substrate pair Acetoin: Dichlorophenolindophenol Oxidoreductase from Bacillus licheniformis / methyl acetoin was efficiently exploited for the preparation of optically active phenyl acetyl carbinols ((S) -PACs). In addition, the same enzyme / substrate pair was demonstrated to be extremely effective in the synthesis of dissymmetric acyloins. At the end of my doctoral course, during my period abroad in the group of Prof. Darren J. Dixon at the University of Oxford, I was involved in a research program dealing with the activation of amides promoted by Iridium complexes. In this regard, a new methodology was developed for the synthesis of substituted pyrrolidines, which were obtained through 1,3-dipolar cyclization reactions between acrylates and azomethine ylides generated in situ by catalysis with the Vaska complex in a reductive environment.La progettazione di nuove reazioni che permettono la formazione di legami carbonio-carbonio è sicuramente il campo principale in cui si sono focalizzati gli sforzi dei chimici organici negli ultimi quarant’anni. In aggiunta, l’indubbio beneficio portato dalla catalisi in tale ambito ha reso possibile l’esplorazione di nuove reattività prima sconosciute, che hanno spianato la strada alla sintesi di molecole complesse, in maniera sempre più efficiente. Su questa linea, il nostro gruppo si è inserito da anni con la premessa di esplorare in maniera critica la reattività che porta all’inversione della naturale polarità nei substrati, e durante il mio periodo di dottorato l’attività svolta ha previsto l’indagine di tale reattività attraverso i suoi due approcci più importanti (organocatalisi e biocatalisi). La via organocatalitica è stata impiegata con successo nella sintesi di imidazoline-2-tioni mediante un processo domino che ha coinvolto la formazione di un nuovo legame carbonio-carbonio, tramite una reazione aza-benzoinica promossa da un carbene N-eterociclico (NHC acronimo del termine inglese N-Heterocyclic Carbene). A seguire è stato messo a punto un protocollo per la dearomatizzazione di sali di piridinio, attivati da un gruppo elettron-attrattore in posizione 3 dell’anello. Questi ultimi hanno ricoperto il ruolo di elettrofili nell’addizione di aldeidi attivate da NHC chirali. Ed infine, l’ultimo lavoro inerente l’organocatalisi, ha riguardato la desimmetrizzazione di 1,4-diidropiridine tramite catalisi da NHC chirali in ambiente ossidativo. Nell’ambito della biocatalisi la coppia enzima/substrato, Acetoin:Dichlorophenolindophenol Oxidoreductase from Bacillus licheniformis / metil acetoino, è stata impiegata efficacemente nella preparazione di fenil acetil carbinoli otticamente attivi ((S)-PAC). In aggiunta, la medesima coppia enzima/substrato si è rivelata essere estremamente efficiente per sintesi enantioselettiva di aciloini dissimmetrici. Al termine del mio percorso dottorale, durante il mio periodo svolto all’estero presso il gruppo del Prof. Darren J. Dixon (Università di Oxford), mi sono occupato dell’attivazione di ammidi mediante complessi di Iridio. Nella fattispecie è stata sviluppata una metodologia che porta alla sintesi di pirrolidine sostituite, attraverso una reazione di ciclizzazione 1,3-dipolare, resa possibile dalla formazione in situ di azometinilidi grazie alla reattività del complesso di Vaska in ambiente riduttivo

Deep Eutectic Solvents: Alternative reaction media for organic oxidation reactions

Deep eutectic solvents (DESs) have emerged as an alternative to ionic liquids (ILs). DESs share with ILs some appealing features, such as low vapor pressure, capability to dissolve reagents insoluble in common organic solvents, and the possibility to tune the overall pH of the medium by replacing one of the constituents of the mixture. Furthermore, DESs can be prepared by combining molecules that come from natural sources (i.e., glycerol, glucose), making them biodegradable. DESs have already been used for a variety of reactions and protocols since they were reported for the first time by A. P. Abbott, G. Capper, D. L. Davies, R. K. Rasheed and V. Tambyrajah, Chem. Commun., 2003, 70, and among the reactions studied, organic oxidation has recently gained much attention. In particular, the recyclability of these ionic compounds makes it possible to achieve anchoring of organic oxidants, such as TEMPO and peroxydisulfate, directly onto one species of the DES mixture components. In addition, their solubility properties play a crucial role in organic oxidation since DESs have the ability to dissolve both organic lipophilic and hydrophilic species, making the oxidation of organic compounds mediated by hydrogen peroxide more efficient. Herein we report the state of the art of this developing field, focusing on the benefits of substituting common organic solvents with DESs, especially in terms of sustainability, enhancement of reactivity, and recyclability

Deep eutectic solvents: alternative reaction media for organic oxidation reactions

Deep eutectic solvents (DESs) have emerged as an alternative to ionic liquids (ILs). DESs share with ILs some appealing features, such as low vapor pressure, capability to dissolve reagents insoluble in common organic solvents, and the possibility to tune the overall pH of the medium by replacing one of the constituents of the mixture. Furthermore, DESs can be prepared by combining molecules that come from natural sources (i.e., glycerol, glucose), making them biodegradable. DESs have already been used for a variety of reactions and protocols since they were reported for the first time by A. P. Abbott, G. Capper, D. L. Davies, R. K. Rasheed and V. Tambyrajah, Chem. Commun., 2003, 70, and among the reactions studied, organic oxidation has recently gained much attention. In particular, the recyclability of these ionic compounds makes it possible to achieve anchoring of organic oxidants, such as TEMPO and peroxydisulfate, directly onto one species of the DES mixture components. In addition, their solubility properties play a crucial role in organic oxidation since DESs have the ability to dissolve both organic lipophilic and hydrophilic species, making the oxidation of organic compounds mediated by hydrogen peroxide more efficient. Herein we report the state of the art of this developing field, focusing on the benefits of substituting common organic solvents with DESs, especially in terms of sustainability, enhancement of reactivity, and recyclability

Solvent effects in the homogeneous catalytic reduction of propionaldehyde with aluminium isopropoxide catalyst: New insights from PFG NMR and NMR relaxation studies

Solvent effects in homogeneous catalysis are known to affect catalytic activity. Whilst these effects are often described using qualitative features, such as Kamlet‐Taft parameters, experimental tools able to quantify and reveal in more depth such effects have remained unexplored. In this work, PFG NMR diffusion and T1 relaxation measurements have been carried out to probe solvent effects in the homogeneous catalytic reduction of propionaldehyde to 1‐propanol in the presence of aluminium isopropoxide catalyst. Using data on diffusion coefficients it was possible to estimate trends in aggregation of different solvents. The results show that solvents with a high hydrogen‐bond accepting ability, such as ethers, tend to form larger aggregates, which slow down the molecular dynamics of aldehyde molecules, as also suggested by T1 measurements, and preventing their access to the catalytic sites, which results in the observed decrease of catalytic activity. Conversely, weakly interacting solvents, such as alkanes, do not lead to the formation of such aggregates, hence allowing easy access of the aldehyde molecules to the catalytic sites, resulting in higher catalytic activity. The work reported here is a clear example on how combining traditional catalyst screening in homogeneous catalysis with NMR diffusion and relaxation time measurements can lead to new physico‐chemical insights into such systems by providing data able to quantify aggregation phenomena and molecular dynamics