Targeting the Antifungal Activity of Carbon Dots against Candida albicans Biofilm Formation by Tailoring Their Surface Functional Groups.

Carbon dots (CDs) are an emerging class of carbon nanoparticles, which for their characteristics have found applications in many fields such as catalysis, materials and biomedicine. Within this context, the application of CDs as antibacterial agents has received much attention in very recent years, while their use as antifungal nanoparticles has been scarcely investigated. Here we report a systematic investigation of the surface functional groups of CDs to study their influence on these nanoparticles' against Candida albicans. Three classes of CDs have been synthesised and fully characterized. A thorough in vitro and in vivo biological screening against C. albicans was performed to test their antifungal, antiadhesion and antibiofilm formation activities. Moreover, the interaction with C. albicans cells was investigated by microscopic analysis. Our results evidence how the presence of a positively polarised surface results crucial for the internalization into COS-7 cells. Positively charged nanoparticles were also able to inhibit adhesion and biofilm formation, to interact with the cellular membrane of C. albicans, and to increase the survival of G. mellonella infected larvae after the injection with positive nanoparticles. The antifungal activity of CDs and their extremely low toxicity may represent a new strategy to combat infections sustained by C.albicans.

Chlamydomonas reinhardtii: A Factory of Nutraceutical and Food Supplements for Human Health.

Chlamydomonas reinhardtii (C. reinhardtii) is one of the most well-studied microalgae organisms that revealed important information for the photosynthetic and metabolic processes of plants and eukaryotes. Numerous extensive studies have also underpinned its great potential as a biochemical factory, capable of producing various highly desired molecules with a direct impact on human health and longevity. Polysaccharides, lipids, functional proteins, pigments, hormones, vaccines, and antibodies are among the valuable biomolecules that are produced spontaneously or under well-defined conditions by C. reinhardtii and can be directly linked to human nutrition and diet. The aim of this review is to highlight the recent advances in the field focusing on the most relevant applications related to the production of important biomolecules for human health that are also linked with human nutrition and diet. The limitations and challenges are critically discussed along with the potential future applications of C. reinhardtii biomass and processed products in the field of nutraceuticals and food supplements. The increasing need for high-value and low-cost biomolecules produced in an environmentally and economy sustainable manner also underline the important role of C. reinhardtii.

N-Acetyl-l-phenylalanine Racemization during TBTU Amidation: An In-Depth Study for the Synthesis of Anti-Inflammatory 2-(N-Acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA).

A thorough study on the amidation conditions of N-acetyl-l-phenylalanine using TBTU and various bases is reported for the synthesis of 2-(N-acetyl)-l-phenylalanylamido-2-deoxy-d-glucose (NAPA), a promising drug for the treatment of joints diseases. TBTU-mediated diastereoselective amidation reaction with 1,3,4,6-tetra-O-acetyl-ß-d-glucosamine always gave racemization of N-acetyl-l-phenylalanine. The stereochemical retention under amidation conditions was studied in detail in the presence of difference bases and via other control experiments, evidencing the possibility to reduce racemization using pyridine as base.

Stereoselective Synthesis of Spiro-Decalin Oxindole Derivatives via Sequential Organocatalytic Michael-Domino Michael/Aldol Reaction.

A highly stereoselective procedure for the synthesis of spiro-polycyclic oxindoles bearing five contiguous stereogenic centers including two tetrasubstituted carbons has been developed. Under sequential organocatalysis performed by a pyrrolidine-based organocatalyst and DBU, a highly atom-economical Michael-domino Michael/aldol reaction sequence was optimized, yielding variously functionalized spiro-decalin oxindoles with excellent stereoselectivity (>99:1 dr, up to 92% ee).

Anharmonic Aspects in Vibrational Circular Dichroism Spectra from 900 to 9000 cm-1 for Methyloxirane and Methylthiirane.

Vibrational circular dichroism (VCD) spectra and the corresponding IR spectra of the chiral isomers of methyloxirane and of methylthiirane have been reinvestigated, both experimentally and theoretically, with particular attention to accounting for anharmonic corrections, as calculated by the GVPT2 approach. De novo recorded VCD spectra in the near IR (NIR) range regarding CH-stretching overtone transitions, together with the corresponding NIR absorption spectra, were also considered and accounted for, both with the GVPT2 and with the local mode approaches. Comparison of the two methods has permitted us to better describe the nature of active "anharmonic" modes in the two molecules and the role of mechanical and electrical anharmonicity in determining the intensities of VCD and IR/NIR data. Finally, two nonstandard IR/NIR regions have been investigated: the first one about ≈2000 cm-1, involving mostly two-quanta bending mode transitions, the second one between 7000 and 7500 cm-1 involving three-quanta transitions containing CH-stretching overtones and HCC/HCH bending modes.

Stemodane Diterpenes and Diterpenoids: Isolation, Structure Elucidation, Biogenesis, Biosynthesis, Biological Activity, Biotransformations, Metabolites and Derivatives Biological Activity, Rearrangements.

The scientific activity carried out over forty-five years on stemodane diterpenes and diterpenoids structure elucidation, biogenesis, biosynthesis, biological activity and biotransformations was reviewed.

Structural features of selected protic ionic liquids based on a super-strong base.

Protic ionic liquids (PIL) were prepared from a super-strong base 1,7-diazabicyclo[5.4.0]undec-7-ene (DBU) and super-strong acids, trifluoromethane sulfonic acid (TfOH), and (trifluoromethanesulfonyl)-(nonafluorobutylsulfonyl)imide, (IM14H), ([DBUH][TfO] and [DBUH][IM14], respectively; the latter for the first time) and their chemical and physical properties and structural features have been explored using a synergy of experimental and computational tools. The short range order in neat DBU, as well as the long range structural correlations induced by charge correlation and hydrogen bonding interactions in the ionic liquids, have been explored under ambient conditions, where these compounds are proposed for a variety of applications. Similar to other [DBUH]-based PILs, the probed ones behave as good ionic liquids. Molecular dynamics-rationalised X-ray diffraction patterns show the major role played by hydrogen bonding in affecting morphology in these systems. Additionally, we find further evidence for the existence of fluorous domains in [DBUH][IM14], thus potentially extending the range of applications for these PILs.

Stemarane Diterpenes and Diterpenoids.

: In this article the scientific activity carried out on stemarane diterpenes and diterpenoids, isolated over the world from various natural sources, was reviewed. The structure elucidation of stemarane diterpenes and diterpenoids was reported, in addition to their biogenesis and biosynthesis. Stemarane diterpenes and diterpenoids biotransformations and biological activity was also taken into account. Finally the work leading to the synthesis and enantiosynthesis of stemarane diterpenes and diterpenoids was described.

Unexpected Racemization in the Course of the Acetalization of (+)-(S)-5-Methyl-Wieland-Miescher Ketone with 1,2-Ethanediol and TsOH under Classical Experimental Conditions.

(+)-(S) and (-)-(R)-5-methyl-Wieland-Miescher ketone (+)-1 and (-)-1, are important synthons in the diastereo and enantioselective syntheses of biological and/or pharmacological interesting compounds. A key step in these syntheses is the chemoselective C(1)O acetalization to (+)-5 and (-)-5, respectively. Various procedures for this transformation have been described in the literature. Among them, the classical procedure based on the use of 1,2-ethanediol and TsOH in refluxing benzene in the presence of a Dean-Stark apparatus. Within our work on bioactive natural products, it occurred to us to observe the partial racemization of (+)-5 in the course of the acetalization of (+)-1 by means of the latter methodology. Aiming to investigate this drawback, which, to our best knowledge, has no precedents in the literature, we acetalized with 1,2-ethanediol and TsOH in refluxing benzene and in the presence of a Dean-Stark apparatus under various experimental conditions, enantiomerically pure (+)-1. It was found that the extent of racemization depends on the TsOH/(+)-1 and 1,2-ethanediol/(+)-1 ratios. Mechanism hypotheses for this partial and unexpected racemization are provided.

Proof of the Structure of the Stemodia chilensis Tetracyclic Diterpenoid (+)-19-Acetoxystemodan-12-ol by Synthesis from (+)-Podocarpic Acid: X-ray Structure Determination of a Key Intermediate.

The first synthesis of (+)-19-acetoxystemodan-12-ol (1), a stemodane diterpenoid isolated from Stemodia chilensis, is described. The structure was supported by an X-ray crystallographic analysis of intermediate (+)-9a, which confirmed the proposed structure and excluded the structure of (-)-19-hydroxystemod-12-ene as a possible candidate for the Chilean Calceolaria diterpenoid to which the (-)-19-hydroxystemar-13-ene structure (9b) had been erroneously assigned.

(+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †.

In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned.

Two different models to predict ionic-liquid diffraction patterns: fixed-charge versus polarizable potentials.

This study reports the performance of classical molecular dynamics (MD) in predicting the X-ray diffraction patterns of butylammonium nitrate (BAN) and two derivatives, 4-hydroxybutan-1-ammonium nitrate (4-HOBAN) and 4-methoxybutan-1-ammonium nitrate (4-MeOBAN). The structure functions and radial distribution functions obtained from energy-dispersive X-ray diffraction spectra, recorded newly for BAN and for the first time for 4-MeOBAN and 4-HOBAN, are compared with the corresponding quantities calculated from MD trajectories, to access information on the morphology of these liquids. The different behavior of two force fields, a polarizable multipole force field and a fixed-charge one supplemented by an explicit three-body term, is shown. The three-body force field proves to be superior in reproducing the intermediate q range, for which the polarizable force field gives the wrong peak position and intensities. In addition, both models can correctly account for the presence or absence of a low q peak in the scattering patterns.

Interaction of a long alkyl chain protic ionic liquid and water.

A combined experimental/theoretical approach has been used to investigate the role of water in modifying the microscopic interactions characterizing the optical response of 1-butyl-ammonium nitrate (BAN) water solutions. Raman spectra, dominated by the signal from the protic ionic liquid, were collected as a function of the water content, and the corresponding spatial organization of the ionic couples, as well as their local arrangement with water molecules, was studied exploiting classical molecular dynamics calculations. High quality spectroscopic data, combined with a careful analysis, revealed that water affects the vibrational spectrum BAN in solution: as the water concentration is increased, peaks assigned to stretching modes show a frequency hardening together with a shape narrowing, whereas the opposite behavior is observed for peaks assigned to bending modes. Calculation results clearly show a nanometric spatial organization of the ionic couples that is not destroyed on increasing the water content at least within an intermediate range. Our combined results show indeed that small water concentrations even increase the local order. Water molecules are located among ionic couples and are closer to the anion than the cation, as confirmed by the computation of the number of H-bonds which is greater for water-anion than for water-cation. The whole results set thus clarifies the microscopic scenario of the BAN-water interaction and underlines the main role of the extended hydrogen bond network among water molecules and nitrate anions.

Oxime metathesis: tuneable and versatile chemistry for dynamic networks.

Oxime chemistry has emerged as a versatile tool for use in a wide range of applications. In particular, the combination of oximes with esters and urethanes has enabled the realisation of Covalent Adaptable Networks (CANs) with improved and tunable dynamic properties. Nevertheless, an exclusively oxime-based chemistry has not yet been explored in the fabrication of CANs. In this work, we investigate the mechanism of the acid-catalysed dynamic exchange of oximes. We propose a metathesis mechanism that is well supported by both experimental and computational studies, which highlight the importance of the substituent effect on the exchange reaction kinetics. Then, as a proof of concept, we incorporate oxime groups into a cross-linked polymeric material and demonstrate the ability of oxime-based polymers to be reprocessed under acid catalysis while maintaining their structural integrity.

Rice Phytoalexins: Half a Century of Amazing Discoveries; Part I: Distribution, Biosynthesis, Chemical Synthesis, and Biological Activities.

Cultivated rice is a staple food for more than half of the world's population, providing approximately 20% of the world's food energy needs. A broad spectrum of pathogenic microorganisms causes rice diseases leading to huge yield losses worldwide. Wild and cultivated rice species are known to possess a wide variety of antimicrobial secondary metabolites, known as phytoalexins, which are part of their active defense mechanisms. These compounds are biosynthesized transiently by rice in response to pathogens and certain abiotic stresses. Rice phytoalexins have been intensively studied for over half a century, both for their biological role and their potential application in agronomic and pharmaceutical fields. In recent decades, the growing interest of the research community, combined with advances in chemical, biological, and biomolecular investigation methods, has led to a notable acceleration in the growth of knowledge on rice phytoalexins. This review provides an overview of the knowledge gained in recent decades on the diversity, distribution, biosynthesis, chemical synthesis, and bioactivity of rice phytoalexins, with particular attention to the most recent advances in this research field.

Thymol-Functionalized Hyaluronic Acid as Promising Preservative Biomaterial for the Inhibition of Candida albicans Biofilm Formation.

Hyaluronic acid (HA) is a naturally occurring biopolymer that has been employed for a plethora of medicinal applications. Nevertheless, as HA is a natural polysaccharide, it can be a substrate able to promote microbial growth and proliferation. Biopolymer-drug conjugates have gained attention over the years to overcome drawbacks of each single component. Within this context, thymol (Thy), a phenolic compound occurring in essential oils (EOs) extracted from Thymus and Origanum, has been largely studied for its antimycotic applications. However, it is characterized by a low water solubility and moderate cytotoxicity. Herein, we report an innovative HA-thymol conjugate (HA-Thy) biomaterial to circumvent the drawbacks of free thymol use by providing the polymer conjugate with the beneficial properties of both components. Preliminary biological tests evidenced the decrease of thymol cytotoxicity for the HA-Thy conjugate, paired with a promising antibiofilm formation activity against Candida albicans, similar to pure thymol, highlighting its potential application as a preservative biomaterial in formulations.

Regio- and diastereoselective synthesis and X-ray structure determination of (+)-2-deoxyoryzalexin S from (+)-podocarpic acid. Structural nonidentity with its nominal natural isolated enantiomer.

(+)-2-Deoxyoryzalexin S (1), the nominal enantiomer of a diterpenoid isolated in Chile from Calceolaria species, was regio- and diastereoselectively synthesized from (+)-podocarpic acid. (+)-2-Deoxyoryzalexin S (1) was characterized also as its acetyl derivative, (+)-2, whose structure was confirmed by X-ray crystallographic analysis. Surprisingly, comparison of the data recorded for (+)-1 and (+)-2 and those reported in the literature for the Calceolaria isolated diterpenoid 1 and its derivative (-)-2 showed some differences, suggesting that the latter do not possess the proposed structures.

Self-Healing and Reprocessable Oleic Acid-Based Elastomer with Dynamic S-S Bonds as Solvent-Free Reusable Adhesive on Copper Surface.

In the last decade, the application of dynamic covalent chemistry in the field of polymeric materials has become the subject of an increasing number of studies, gaining applicative relevance. This is due to the fact that polymers containing dynamic functions possess a structure that affords reprocessability, recyclability and peculiar self-healing properties inconceivable for "classic" polymer networks. Consequently, the synthesis of a dynamic covalent chemistry-based polymer and its chemical, thermal, and mechanical characterizations are reported in the present research. In particular, oleic acid has been used as starting material to follow the founding principles of the circular economy system and, thanks to the aromatic disulfide component, which is the foundation of the material dynamic characteristics, the obtained polymer resulted as being reprocessable and self-healable. Moreover, the polymer can strongly interact with copper surfaces through the formation of stable Cu-S bonds. Then, the application of the polymer as a solvent-free reusable adhesive for copper was investigated by lap joint shear tests and comparisons with the properties of an analogous material, devoid of the disulfide bonds, were conducted.

Diastereoselective total synthesis of (+)-13-stemarene by fourth generation methods: a formal total synthesis of (+)-18-deoxystemarin.

The problem of constructing diastereoselectively the C/D ring system of stemarane diterpenes from a bicyclo[2.2.2]octane intermediate was solved resulting in very simple synthesis of (+)-13-stemarene 1. The obtaining of the latter represents also a formal synthesis of (+)-18-deoxystemarin 2. In the key step, the epimeric mixture 10, dissolved in toluene, was converted by the action of TsOH into (+)-stemar-13-en-15-one 28.

Impact of Environmental Factors on Stilbene Biosynthesis.

Stilbenes are a small family of polyphenolic secondary metabolites that can be found in several distantly related plant species. These compounds act as phytoalexins, playing a crucial role in plant defense against phytopathogens, as well as being involved in the adaptation of plants to abiotic environmental factors. Among stilbenes, trans-resveratrol is certainly the most popular and extensively studied for its health properties. In recent years, an increasing number of stilbene compounds were subjected to investigations concerning their bioactivity. This review presents the most updated knowledge of the stilbene biosynthetic pathway, also focusing on the role of several environmental factors in eliciting stilbenes biosynthesis. The effects of ultraviolet radiation, visible light, ultrasonication, mechanical stress, salt stress, drought, temperature, ozone, and biotic stress are reviewed in the context of enhancing stilbene biosynthesis, both in planta and in plant cell and organ cultures. This knowledge may shed some light on stilbene biological roles and represents a useful tool to increase the accumulation of these valuable compounds.