Tailored functionalization of natural phenols to improve biological activity

Phenols are widespread in nature, being the major components of several plants and essential oils. Natural phenols' anti-microbial, anti-bacterial, anti-oxidant, pharmacological and nutritional properties are, nowadays, well established. Hence, given their peculiar biological role, numerous studies are currently ongoing to overcome their limitations, as well as to enhance their activity. In this review, the functionalization of selected natural phenols is critically examined, mainly highlighting their improved bioactivity after the proper chemical transformations. In particular, functionalization of the most abundant naturally occurring monophenols, diphenols, lipidic phenols, phenolic acids, polyphenols and curcumin derivatives is explored

A stoichiometric solvent-free protocol for acetylation reactions

Considering the remarkable relevance of acetylated derivatives of phenols, alcohols, and aryl and alkyl thiols in different areas of biology, as well as in synthetic organic chemistry, a sustainable solvent-free approach to perform acetylation reactions is proposed here. Acetylation reactions are classically performed using excess of acetic anhydride (Ac2O) in solvent-free conditions or by eventually working with stoichiometric amounts of Ac2O in organic solvents; both methods require the addition of basic or acid catalysts to promote the esterification. Therefore, they usually lead to the generation of high amounts of wastes, which sensibly raise the E-factor of the process. With the aim to develop a more sustainable system, a solvent-free, stoichiometric acetylation protocol is, thus, proposed. The naturally occurring phenol, thymol, can be converted to the corresponding-biologically active-ester with good yields, in the presence of 1% of VOSO4. Interestingly, the process can be efficiently adopted to synthesize other thymyl esters, as well as to perform acetylation of alcohols and aryl and alkyl thiols. Remarkably, a further improvement has been achieved replacing Ac2O with its greener alternative, isopropenyl acetate (IPA)

Unveiling KuQuinone redox species: an electrochemical and computational cross study

The study of the electrochemical properties of variegated quinones is a fascinating topic in chemistry. In fact, redox reactions occurring with quinoid scaffolds are essential for most of their applications in biological systems, in photoelectrochemical devices, and in many other fields. In this paper, a detailed investigation of KuQuinones' redox behavior is presented. The distinctiveness of such molecules is the presence in the structure of two condensed naphthoquinone units, which implies the possibility to undergo multiple one-electron reduction processes. Solvent, supporting electrolyte, and hydrogen bond donor species effects have been elucidated. Changing the experimental parameters provoked significant shift of the redox potential for each reduction process. In particular, additions of 2,2,2-trifluoroethanol as a hydrogen bond donor in solution as well as Lewis acid coordination were crucial to obtain important shifts of the redox potentials toward more favorable values. UV-vis-NIR spectroelectrochemical experiments and DFT calculations are also presented to clarify the nature of the reduced species in solution

Towards the “Eldorado” of pKa Determination: A Reliable and Rapid DFT Model

The selection of a “perfect tool” for the theoretical determination of acid-base dissociation constants (Ka) is still puzzling. Recently, we developed a user-friendly model exploiting CAM-B3LYP for determining pKa with impressive reliability. Herein, a new challenge is faced, examining a panel of functionals belonging to different rungs of the “Jacob’s ladder” organization, which classifies functionals according to their level of theory. Specifically, meta-generalized gradient approximations (GGAs), hybrid-GGAs, and the more complex range-separated hybrid (RSH)-GGAs were investigated in predicting the pKa of differently substituted carboxylic acids. Therefore, CAM-B3LYP, WB97XD, B3PW91, PBE1PBE, PBEPBE and TPSSTPSS were used, with 6-311G+(d,p) as the basis set and the solvation model based on density (SMD). CAM-B3LYP showed the lowest mean absolute error value (MAE = 0.23) with relatively high processing time. PBE1PBE and B3PW91 provided satisfactory predictions (MAE = 0.34 and 0.38, respectively) with moderate computational time cost, while PBEPBE, TPSSTPSS and WB97XD led to unreliable results (MAE > 1). These findings validate the reliability of our model in predicting carboxylic acids pKa, with MAE well below 0.5 units, using a simplistic theoretical level and a low-cost computational approach

An accurate approach for computational pKa determination of phenolic compounds

Computational chemistry is a valuable tool, as it allows for in silico prediction of key parameters of novel compounds, such as pKa. In the framework of computational pKa determination, the literature offers several approaches based on different level of theories, functionals and continuum solvation models. However, correction factors are often used to provide reliable models that adequately predict pKa. In this work, an accurate protocol based on a direct approach is proposed for computing phenols pKa. Importantly, this methodology does not require the use of correction factors or mathematical fitting, making it highly practical, easy to use and fast. Above all, DFT calculations performed in the presence two explicit water molecules using CAM-B3LYP functional with 6-311G+dp basis set and a solvation model based on density (SMD) led to accurate pKa values. In particular, calculations performed on a series of 13 differently substituted phenols provided reliable results, with a mean absolute error of 0.3. Furthermore, the model achieves accurate results with -CN and -NO2 substituents, which are usually excluded from computational pKa studies, enabling easy and reliable pKa determination in a wide range of phenols

Spinal vascular lesions: anatomy, imaging techniques and treatment

Vascular lesions of the spinal cord are rare but potentially devastating conditions whose accurate recognition critically determines the clinical outcome. Several conditions lead to myelopathy due to either arterial ischemia, venous congestion or bleeding within the cord. The clinical presentation varies, according with the different aetiology and mechanism of damage

Artificial photosynthesis: photoanodes based on polyquinoid dyes onto mesoporous tin oxide surface

Dye-sensitized photoelectrochemical cells represent an appealing solution for artificial photosynthesis, aimed at the conversion of solar light into fuels or commodity chemicals. Extensive efforts have been directed towards the development of photoelectrodes combining semiconductor materials and organic dyes; the use of molecular components allows to tune the absorption and redox properties of the material. Recently, we have reported the use of a class of pentacyclic quinoid organic dyes (KuQuinone) chemisorbed onto semiconducting tin oxide as photoanodes for water oxidation. In this work, we investigate the effect of the SnO2 semiconductor thickness and morphology and of the dye-anchoring group on the photoelectrochemical performance of the electrodes. The optimized materials are mesoporous SnO2 layers with 2.5 mu m film thickness combined with a KuQuinone dye with a 3-carboxylpropyl-anchoring chain: these electrodes achieve light-harvesting efficiency of 93% at the maximum absorption wavelength of 533 nm, and photocurrent density J up to 350 mu A/cm(2) in the photoelectrochemical oxidation of ascorbate, although with a limited incident photon-to-current efficiency of 0.075%. Calculations based on the density functional theory (DFT) support the role of the reduced species of the KuQuinone dye via a proton-coupled electron transfer as the competent species involved in the electron transfer to the tin oxide semiconductor. Finally, a preliminary investigation of the photoelectrodes towards benzyl alcohol oxidation is presented, achieving photocurrent density up to 90 mu A/cm(2) in acetonitrile in the presence of N-hydroxysuccinimide and pyridine as redox mediator and base, respectively. These results support the possibility of using molecular-based materials in synthetic photoelectrochemistry.[GRAPHICS]

Midterm follow-up after embolization of intracranial aneurysms proximal to the circle of Willis with the Silk Vista flow diverter: the I-MAMA registry

Purpose: The aim of this registry was to assess technical success, procedural safety and mid- to long-term follow-up results of the Silk Vista “Mama” (SVM) flow diverter (BALT, Montmorency, France) for the treatment of proximal intracranial aneurysms. Methods: Between August 2020 and March 2022, data from nine Italian neurovascular centres were collected. Data included patients’ clinical presentation, aneurysms’ size, location and status, technical details, overall complications and mid- to long-term angiographic follow-up. Results: Forty-eight aneurysms in 48 patients were treated using the SVM. Most aneurysms were small (≤ 10 mm: no. 29, 60%) and unruptured (no. 31, 65%); 13 aneurysms were recurrent after coiling or clipping. 37/48 aneurysms involved the internal carotid artery (77%). Optimal opening and complete wall apposition of the device were achieved in 46 out of 48 cases (96%). Four intra- or periprocedural complications occurred (two thrombotic complications successfully resolved, one cerebellar ischemia, one perirenal hematoma), without new neurological deficit. No significant intra-stent stenosis or stent displacement was observed during follow-up. No FD-related morbidity nor mortality was reported. At midterm (6–12 months) to long-term (> 12 months) follow-up, complete aneurysm occlusion (OKM D) was achieved in 76% of cases. Eighty-eight percent of patients had complete aneurysm occlusion or entry remnant (OKM D + C). Conclusions: Our experience suggests that the new generation of low-profile SVM flow diverter for the treatment of proximal intracranial aneurysms is safe and effective, with low rates of intraprocedural complications and acceptable mid- to long-term occlusion rate