Modelling complex bimolecular reactions in a condensed phase: the case of phosphodiester hydrolysis

Background: the theoretical modelling of reactions occurring in liquid phase is a research line of primary importance both in theoretical-computational chemistry and in the context of organic and biological chemistry. Here we present the modelling of the kinetics of the hydroxide-promoted hydrolysis of phosphoric diesters. Method: the theoretical-computational procedure involves a hybrid quantum/classical approach based on the perturbed matrix method (PMM) in conjunction with molecular mechanics. Results: the presented study reproduces the experimental data both in the rate constants and in the mechanistic aspects (C-O bond vs. O-P bond reactivity). The study suggests that the basic hydrolysis of phosphodiesters occurs through a concerted ANDN mechanism, with no formation of penta-coordinated species as reaction intermediates. Conclusions: the presented approach, despite the approximations, is potentially applicable to a large number of bimolecular transformations in solution and therefore leads the way to a fast and general method to predict the rate constants and reactivities/selectivities in complex environments

Turning renewable feedstocks into a valuable and efficient chiral phosphate salt catalyst

Solketal, the chiral acetonide of glycerol, has been employed as the starting material in the design of a novel punctually chiral phosphate sodium salt for catalytic applications in organic and asymmetric synthesis. The racemate and the two enantiomers of the substrate are economic and commercially available, straightforwardly prepared in high yields from naturally occurring feedstocks. Therefore, remarkably, both enantiomers of the final catalyst can be synthesized by simple procedures in high yield and in compliance with several principles of green chemistry. To further demonstrate the usefulness of the novel catalyst, its application in a solventless protocol for cyanohydrin synthesis from a series of aldehydes has been presented

Organocatalyzed addition to activated C=C bonds

In this chapter, several examples of organocatalyzed additions to C=C bonds carried out through a domino approach are reviewed, from the early examples to recent applications of these strategies in industry

An all-glass microfluidic network with integrated amorphous silicon photosensors for on-chip monitoring of enzymatic biochemical assay

A lab-on-chip system, integrating an all-glass microfluidics and on-chip optical detection, was developed and tested. The microfluidic network is etched in a glass substrate, which is then sealed with a glass cover by direct bonding. Thin film amorphous silicon photosensors have been fabricated on the sealed microfluidic substrate preventing the contamination of the micro-channels. The microfluidic network is then made accessible by opening inlets and outlets just prior to the use, ensuring the sterility of the device. The entire fabrication process relies on conventional photolithographic microfabrication techniques and is suitable for low-cost mass production of the device. The lab-on-chip system has been tested by implementing a chemiluminescent biochemical reaction. The inner channel walls of the microfluidic network are chemically functionalized with a layer of polymer brushes and horseradish peroxidase is immobilized into the coated channel. The results demonstrate the successful on-chip detection of hydrogen peroxide down to 18 mu M by using luminol and 4-iodophenol as enhancer agent

Suicidal ideation and suicide commitment in Health Care Workers during COVID-19 pandemic: a review of the literature

Introduction: Suicide represents an important public health concern since it leads to more annual deaths globally than violence, war and natural disasters combined. It is evident that during this pandemic year the phenomenon acquires even greater importance especially in the categories at risk, such as health care workers (HCWs). The aim of this review is to analyze literature evidence regarding health care providers' suicidal ideation (SI) and suicide commitment during the first year of the COVID-19 pandemic. Methods: International databases and digital worldwide media reports were screened between March 2020 and March 2021. The authors conducted a systematic review and described evidence using a narrative approach with some focus points based on the PICO framework. Inclusion or exclusion of literature is done according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations. Results: What emerged is a range of SI that varies from 4 to 8% and the main risk factors seem to be loneliness, not having children and personal history of mental disorders. Conclusion: SI, and in worst cases suicide commitment, seem mental health outcomes not to be underestimated, especially in an emergency that is protracting. They require monitoring by health surveillance systems with a goal of prevention and support

Do Autistic Traits Correlate with Post-Traumatic Stress and Mood Spectrum Symptoms among Workers Complaining of Occupational Stress?

The adult autism subthreshold spectrum model appears to be a useful tool for detecting possible vulnerability factors in order to develop mental disorders in the contest of work-related stress. The aim of the present study is to analyze the relationship between autism, mood, and post-traumatic spectrum in a cohort of subjects complaining of work-related stress before the COVID-19 pandemic. The authors carried out a retrospective investigation of both medical records and self-assessment tools of a sample of subjects evaluated at the Occupational Health Department of a University hospital in central Italy. Data showed significant correlations between the AdAS spectrum, TALS-SR, and MOODS total and domain scores. A multiple linear regression evidenced that both the AdAS spectrum and TAL-SR significantly predict the MOODS scores. In particular, mediation analysis showed both a direct and indirect, mediated by TALS-SR, effect of the AdAS Spectrum on the MOODS-SR. These results corroborate the role of autistic traits in influencing the traumatic impact of work-related stress and the development of mood spectrum symptoms

Guanidinium promoted cleavage of phosphoric diesters: Kinetic investigations and calculations provide indications on the operating mechanism

The catalytic activity of the guanidinium units toward the cleavage of phosphoric diesters is deeply investigated both with kinetic experiments and DFT calculations. The first part of the investigation aims to determine how the structure of the substrate (phenyl or alkyl esters) is able to influence the guanidinium-catalyzed hydrolysis changing the mechanism from ANDN to AN+DN. In the cleavage of the DNA model bis(4-nitrophenyl)phospate (BNPP), experimental kinetic data highlight the operation of a guanidine-guanidinium catalytic dyad that can act both intermolecularly and intramolecularly on different molecular scaffolds exhibiting notable values of effective molarity. 31P NMR spectra and DFT investigation provide indication that the deprotonated guanidine involved in such a catalysis acts as a general base in the deprotonation of a water molecule involved in the cleavage, and not as nucleophilic unit. Moreover, DFT calculations were carried out to determine the guanidinium promoted activation energy of pseudorotation. The results indicate a remarkable drop in the activation energy of this process for dialkylphosphate esters explaining, in part, the higher sensitivity of diribonucleoside to the presence of guanidinium-based catalysts compared to the more activated RNA model HPNP

Guanidine-based polymer brushes grafted onto silica nanoparticles as efficient artificial phosphodiesterases

Polymer brushes grafted to the surface of silica nanoparticles were fabricated by atom-transfer radical polymerization (ATRP) and investigated as catalysts in the cleavage of phosphodiesters. The surfaces of silica nanoparticles were functionalized with an ATRP initiator. Surface-initiated ATRP reactions, in varying proportions, of a methacrylate moiety functionalized with a phenylguanidine moiety and an inert hydrophilic methacrylate species afforded hybrid nanoparticles that were characterized with potentiometric titrations, thermogravimetric analysis, and SEM. The activity of the hybrid nanoparticles was tested in the transesterification of the RNA model compound 2-hydroxypropyl para-nitrophenylphosphate (HPNP) and diribonucleoside monophosphates. A high catalytic efficiency and a remarkable effective molarity, thus overcoming the effective molarities previously observed for comparable systems, indicate the existence of an effective cooperation of the guanidine/guanidinium units and a high level of preorganization in the nanostructure. The investigated system also exhibits a marked and unprecedented selectivity for the diribonucleoside sequence CpA. The results presented open up the way for a novel and straightforward strategy for the preparation of supramolecular catalysts