Identification of Bioactive Compounds of Asparagus officinalis L.: Permutation Test Allows Differentiation among “Triguero” and Hybrid Green Varieties

In this study, we determined the phytochemical profile of the Spanish “triguero” asparagus landrace “verde-morado” (Asparagus officinalis L.), a wild traditional landrace, and the improved “triguero” HT-801, together with two commercial green asparagus varieties. For comparison, we used reverse-phase high-performance liquid chromatography coupled with diode array electrospray time-of-flight mass spectrometry (RP-HPLC-DAD-ESI-TOF/MS) followed by a permutation test applied using a resampling methodology valid under a relaxed set of assumptions, such as i.i.d. errors (not necessarily normal) that are exchangeable under the null hypothesis. As a result, we postulate that “triguero” varieties (the improved HT-801 followed by its parent “verde-morado”) have a significantly different phytochemical profile from that of the other two commercial hybrid green varieties. In particular, we found compounds specific to the “triguero” varieties, such as feruloylhexosylhexose isomers, or isorhamnetin-3-O-glucoside, which was found only in the “triguero” variety HT-801. Although studies relating the phytochemical content of “triguero” asparagus varieties to its health-promoting effects are required, this characteristic phytochemical profile can be used for differentiating and revalorizating these asparagus cultivars.     

“Texas-Sized” Molecular Boxes: From Chemistry to Applications

The design and synthesis of novel macrocyclic host molecules continues to attract attention because such species play important roles in supramolecular chemistry. However, the discovery of new classes of macrocycles presents a considerable challenge due to the need to embody by design effective molecular recognition features, as well as ideally the development of synthetic routes that permit further functionalization. In 2010, we reported a new class of macrocyclic hosts: a set of tetracationic imidazolium macrocycles, which we termed “Texas-sized” molecular boxes (TxSBs) in homage to Stoddart’s classic “blue box” (CBPQT⁴⁺). Compared with the rigid blue box, the first generation TxSB displayed considerably greater conformational flexibility and a relatively large central cavity, making it a good host for a variety of electron-rich guests. In this review, we provide a comprehensive summary of TxSB chemistry, detailing our recent progress in the area of anion-responsive supramolecular self-assembly and applications of the underlying chemistry to water purification, information storage, and controlled drug release. Our objective is to provide not only a review of the fundamental findings, but also to outline future research directions where TxSBs and their constructs may have a role to play.     

Synthesis and Fluorescent Properties of Aminopyridines and the Application in “Click and Probing”

Unsubstituted pyridin-2-amine has a high quantum yield and is a potential scaffold for a fluorescent probe. However, the facile access to conjugated highly substituted aminopyridines and the study of their fluorescent properties is scarce. In this paper, synthesis and fluorescent properties of multisubstituted aminopyridines were studied based on a recently developed Rh-catalyzed coupling of vinyl azide with isonitrile to form a vinyl carbodiimide intermediate, following tandem cyclization with an alkyne. An aminopyridine substituted with an azide group as a potential probe was further designed, synthesized, and evaluated. The “clicking-and-probing” experiment of it on BSA protein showed the potential of aminopyridine as a scaffold of a biological probe.     

A Silver Monochrome “Concetto spaziale” by Lucio Fontana: A Spectroscopic Non- and Micro-Invasive Investigation of Materials

In several of his artworks, for instance the Venezie cycle, Fontana employed metallic paints; previous investigations on such materials highlighted the use of different synthetic binders and of thick paint layers below the metal one, having different colours to change the visual perception of the metallic surface. In the present work, a monochrome silver “Concetto spaziale” by the Italo–Argentine artist belonging to a private collection recently gifted to the museum of the Church of San Fedele in Milano, Italy, was investigated to deepen the knowledge of this particular group of Fontana’s paintings. The artwork was initially visually inspected in visible and ultraviolet (UV) light. Subsequently, a non-invasive spectroscopic investigation was performed by X-ray fluorescence (XRF), reflection Fourier-transform infrared (FTIR) and Raman spectroscopy. A minute fragment of silver-coloured paint was taken from the reverse of the painting, near the cut edge, and examined by scanning electron microscopy coupled with energy dispersive X-ray analysis (SEM-EDX) and micro-Fourier-transform Raman (FT-Raman) spectroscopy. The analytical data made it possible to identify the composition of the metallic paint layer and of the underlying dark one, both from the point of view of the pigments and of the binders used, also highlighting the potential of the non-invasive and micro-invasive methods adopted in the investigation.     

Observation of “de Vries-like” properties in bent-core molecules

“de Vries” liquid crystals, defined by a maximum layer shrinkage of ≤1% from the smectic A to C phase transition, are an integral component of ferroelectric liquid crystal (FLC) displays. Bona fide de Vries materials described in the literature are primarily perfluorinated, polysiloxane and polysilane-terminated rod-like (or calamitic) LCs. Herein, for the first time, we report a series of newly designed achiral unsymmetrical bent-core molecules with terminal alkoxy chains exhibiting similar properties to “de Vries” LCs. The new molecular structure is based on the systematic distribution of four phenyl rings attached via ester and imine linkers having 3-amino-2-methylbenzoic acid as the central core with a bent angle of 147°. Detailed microscopic investigations in differently aligned (planar as well as homeotropic) cells along with SAXS/WAXS studies revealed that the materials exhibited a SmA–SmC phase sequence along with the appearance of the nematic phase at higher temperatures. SAXS measurements divulged the layer spacings (d-spacings) and hence, the layer shrinkage was calculated ranging from 0.19% to 0.68% just below the SmA–SmC transition. The variation of the calculated molecular tilt angle (α) derived from the temperature-dependent SAXS data, followed the power law with exponent values 0.29 ± 0.01 and 0.25 ± 0.01 for compounds 1/10 and 1/12, respectively. The experimental values obtained were very close to the theoretically predicted values for the materials with de Vries-like properties. The analysis of temperature-dependent birefringence studies based on the prediction of the Landau theory, showed a dip across the SmA–SmC phase transition typical of compounds exhibiting the de Vries characteristics. The collective results obtained suggest “de Vries” SmA as a probable model for this bent-core system which may find applications in displays.

A simple molecular design of unsymmetrical bent-core molecules exhibiting low layer shrinkage and a dip in the birefringence at the SmA–SmC phase transition, typical characteristics of “de Vries” liquid crystals.     

Using the Method of “Optical Biopsy” of Prostatic Tissue to Diagnose Prostate Cancer

Simple SummaryAnalytical discrimination models of Raman spectra of prostate cancer tissue were constructed by using the projections onto latent structures data analysis (PLS-DA) method for different wavelengths of exciting radiation—532 and 785 nm. These models allowed us to divide the Raman spectra of prostate cancer and the spectra of hyperplasia sites for validation datasets with the accuracy of 70–80%, depending on the specificity value. Meanwhile, for the calibration datasets, the accuracy values reached 100% for the excitation of a laser with a wavelength of 785 nm. Due to the registration of Raman “fingerprints”, the main features of cellular metabolism occurring in the tissue of a malignant prostate tumor were confirmed, namely the absence of aerobic glycolysis, over-expression of markers, and a strong increase in the concentration of cholesterol and its esters, as well as fatty acids and glutamic acid.AbstractThe possibilities of using optical spectroscopy methods in the differential diagnosis of prostate cancer were investigated. Analytical discrimination models of Raman spectra of prostate tissue were constructed by using the projections onto latent structures data analysis(PLS-DA) method for different wavelengths of exciting radiation—532 and 785 nm. These models allowed us to divide the Raman spectra of prostate cancer and the spectra of hyperplasia sites for validation datasets with the accuracy of 70–80%, depending on the specificity value. Meanwhile, for the calibration datasets, the accuracy values reached 100% for the excitation of a laser with a wavelength of 785 nm. Due to the registration of Raman “fingerprints”, the main features of cellular metabolism occurring in the tissue of a malignant prostate tumor were confirmed, namely the absence of aerobic glycolysis, over-expression of markers (FASN, SREBP1, stearoyl-CoA desaturase, etc.), and a strong increase in the concentration of cholesterol and its esters, as well as fatty acids and glutamic acid. The presence of an ensemble of Raman peaks with increased intensity, inherent in fatty acid, beta-glucose, glutamic acid, and cholesterol, is a fundamental factor for the identification of prostate cancer.     

Applications of Hybrid Polymers Generated from Living Anionic Ring Opening Polymerization

Increasingly precise control of polymer architectures generated by “Living” Anionic Ring-Opening Polymerization (Living AROP) is leading to a broad range of commercial advanced material applications, particularly in the area of siloxane macromers. While academic reports on such materials remain sparse, a significant portion of the global population interacts with them on a daily basis—in applications including medical devices, microelectronics, food packaging, synthetic leather, release coatings, and pigment dispersions. The primary driver of this increased utilization of siloxane macromers is their ability to incorporate the properties of silicones into organic structures in a balanced manner. Compared to organic polymers, the differentiating properties of silicones—low T_g, hydrophobicity, low surface energy, and high free molal space—logically lend themselves to applications in which low modulus, release, permeability to oxygen and moisture, and tactile interaction are desired. However, their mechanical, structural and processing properties have until recently precluded practical applications. This review presents applications of “Living” AROP derived polymers from the perspective of historical technology development. Applications in which products are produced on a commercial scale—defined as not only offered for sale, but sold on a recurrent basis—are emphasized. Hybrid polymers with intriguing nanoscale morphology and potential applications in photoresist, microcontact printing, biomimetic soft materials, and liquid crystals are also discussed. Previously unreported work by the authors is provided in the context of this review.     

Electrochemical Determination of the “Furanic Index” in Honey

5-(hydroxymethyl)furan-2-carbaldehyde, better known as hydroxymethylfurfural (HMF), is a well-known freshness parameter of honey: although mostly absent in fresh samples, its concentration tends to increase naturally with aging. However, high quantities of HMF are also found in fresh but adulterated samples or honey subjected to thermal or photochemical stresses. In addition, HMF deserves further consideration due to its potential toxic effects on human health. The processes at the origin of HMF formation in honey and in other foods, containing saccharides and proteins—mainly non-enzymatic browning reactions—can also produce other furanic compounds. Among others, 2-furaldehyde (2F) and 2-furoic acid (2FA) are the most abundant in honey, but also their isomers (i.e., 3-furaldehyde, 3F, and 3-furoic acid, 3FA) have been found in it, although in small quantities. A preliminary characterization of HMF, 2F, 2FA, 3F, and 3FA by cyclic voltammetry (CV) led to hypothesizing the possibility of a comprehensive quantitative determination of all these compounds using a simple and accurate square wave voltammetry (SWV) method. Therefore, a new parameter able to provide indications on quality of honey, named “Furanic Index” (FI), was proposed in this contribution, which is based on the simultaneous reduction of all analytes on an Hg electrode to ca. −1.50 V vs. Saturated Calomel Electrode (SCE). The proposed method, validated, and tested on 10 samples of honeys of different botanical origin and age, is fast and accurate, and, in the case of strawberry tree honey (Arbutus unedo), it highlighted the contribution to the FI of the homogentisic acid (HA), i.e., the chemical marker of the floral origin of this honey, which was quantitatively reduced in the working conditions. Excellent agreement between the SWV and Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) data was observed in all samples considered.     

The highly efficient protein crystallography beamline TLS 13B1 at the National Synchrotron Radiation Research Center

Synchrotron protein crystallography (PX) is one of the most powerful and dominant tools for determining the three-dimensional structures of biological macromolecules. At the National Synchrotron Radiation Research Center, TLS 13B1 is the first dedicated energy-tunable and highly automated PX beamline for efficiently solving de novo protein structures in Taiwan and has been open for users since September 2005. With remote access, user support services, and annual PX training courses over 17 years, the number of user groups at TLS 13B1 has grown from 11 to 139. In total, 1,429 projects were supported, and 2090 experiments were hosted during 67,846 hr of beamtime. This paper describes the photon source, beamline components, experimental station equipment, beamline software, beamline application process, and results from our users.     

“Broken-hearted” carbon bowl via electron shuttle reaction: energetics and electron coupling

Unprecedented one-step C C bond cleavage leading to opening of the buckybowl (π-bowl), that could provide access to carbon-rich structures with previously inaccessible topologies, is reported; highlighting the possibility to implement drastically different synthetic routes to π-bowls in contrast to conventional ones applied for polycyclic aromatic hydrocarbons. Through theoretical modeling, we evaluated the mechanistic pathways feasible for π-bowl planarization and factors that could affect such a transformation including strain and released energies. Through employment of Marcus theory, optical spectroscopy, and crystallographic analysis, we estimated the possibility of charge transfer and electron coupling between “open” corannulene and a strong electron acceptor such as 7,7,8,8-tetracyanoquinodimethane. Alternative to a one-pot solid-state corannulene “unzipping” route, we reported a nine-step solution-based approach for preparation of novel planar “open” corannulene-based derivatives in which electronic structures and photophysical profiles were estimated through the energies and isosurfaces of the frontier natural transition orbitals.

An electron shuttle contributed to breaking corannulene''s heart through a unique one-step reductive C C bond cleavage in the traditionally robust π-bowl. The heartbreak did not stop there as “broken analogs” were developed through a solution-phase route.     

“Click-switch” – one-step conversion of organic azides into photochromic diarylethenes for the generation of light-controlled systems

Diarylethenes (DAEs) are an established class of photochromic molecules, but their effective incorporation into pre-existing targets is synthetically difficult. Here we describe a new class of DAEs in which one of the aryl rings is a 1,2,3-triazole that is formed by “click” chemistry between an azide on the target and a matching alkyne–cyclopentene–thiophene component. This late-stage zero-length linking allows for tight integration of the DAE with the target, thereby increasing the chances for photomodulation of target functions. Nineteen different DAEs were synthesized and their properties investigated. All showed photochromism. Electron-withdrawing groups, and in particular −M-substituents at the triazole and/or thiophene moiety resulted in DAEs with high photo- and thermostability. Further, the chemical nature of the cyclopentene bridge had a strong influence on the behaviour upon UV light irradiation. Incorporation of perfluorinated cyclopentene led to compounds with high photo- and thermostability, but the reversible photochromic reaction was restricted to halogenated solvents. Compounds containing the perhydrogenated cyclopentene bridge, on the other hand, allowed the reversible photochromic reaction in a wide range of solvents, but had on average lower photo- and thermostabilities. The combination of the perhydrocyclopentene bridge and electron-withdrawing groups resulted in a DAE with improved photostability and no solvent restriction. Quantum chemical calculations helped to identify the photoproducts formed in halogenated as well as non-halogenated solvents. For two optimized DAE photoswitches, photostationary state composition and reaction quantum yields were determined. These data revealed efficient photochemical ring closure and opening. We envision applications of these new photochromic diarylethenes in photonics, nanotechnology, photobiology, photopharmacology and materials science.

New photochromic diarylethenes are reported in which one aryl ring is a 1,2,3-triazole that is formed by “click” chemistry between an azide on the target and a matching alkyne–cyclopentene–thiophene component.     

“Click handle”-modified 2′-deoxy-2′-fluoroarabino nucleic acid as a synthetic genetic polymer capable of post-polymerization functionalization

The functions of natural nucleic acids such as DNA and RNA have transcended genetic information carriers and now encompass affinity reagents, molecular catalysts, nanostructures, data storage, and many others. However, the vulnerability of natural nucleic acids to nuclease degradation and the lack of chemical functionality have imposed a significant constraint on their ever-expanding applications. Herein, we report the synthesis and polymerase recognition of a 5-(octa-1,7-diynyl)uracil 2′-deoxy-2′-fluoroarabinonucleic acid (FANA) triphosphate. The DNA-templated, polymerase-mediated primer extension using this “click handle”-modified FANA (cmFANA) triphosphate and other FANA nucleotide triphosphates consisting of canonical nucleobases efficiently generated full-length products. The resulting cmFANA polymers exhibited excellent nuclease resistance and the ability to undergo efficient click conjugation with azide-functionalized molecules, thereby becoming a promising platform for serving as a programmable and evolvable synthetic genetic polymer capable of post-polymerization functionalization.

Polymerase-mediated incorporation of a “click handle”-modified fluoroarabinonucleic acid (cmFANA) triphosphate produces a new class of nuclease-resistant, evolvable genetic polymers that can be functionalized with azide-containing molecules.     

Moving toward a Handheld “Plasma” Spectrometer for Elemental Analysis,Putting the Power of the Atom (Ion) in the Palm of Your Hand

Many of the current innovations in instrument design have been focused on making them smaller, more rugged, and eventually field transportable. The ultimate application is obvious, carrying the instrument to the field for real time sample analysis without the need for a support laboratory. Real time data are priceless when screening either biological or environmental samples, as mitigation strategies can be initiated immediately upon the discovery that contaminant metals are present in a location they were not intended to be. Additionally, smaller “handheld” instruments generally require less sample for analysis, possibly increasing sensitivity, another advantage to instrument miniaturization. While many other instruments can be made smaller just by using available micro-technologies (e.g., eNose), shrinking an ICP-MS or AES to something someone might carry in a backpack or pocket is now closer to reality than in the past, and can be traced to its origins based on a component-by-component evaluation. While the optical and mass spectrometers continue to shrink in size, the ion/excitation source remains a challenge as a tradeoff exists between excitation capabilities and the power requirements for the plasma’s generation. Other supporting elements have only recently become small enough for transport. A systematic review of both where the plasma spectrometer started and the evolution of technologies currently available may provide the roadmap necessary to miniaturize the spectrometer. We identify criteria on a component-by-component basis that need to be addressed in designing a miniaturized device and recognize components (e.g., source) that probably require further optimization. For example, the excitation/ionization source must be energetic enough to take a metal from a solid state to its ionic state. Previously, a plasma required a radio frequency generator or high-power DC source, but excitation can now be accomplished with non-thermal (cold) plasma sources. Sample introduction, for solids, liquids, and gasses, presents challenges for all sources in a field instrument. Next, the interface between source and a mass detector usually requires pressure reduction techniques to get an ion from plasma to the spectrometer. Currently, plasma mass spectrometers are field ready but not necessarily handheld. Optical emission spectrometers are already capable of getting photons to the detector but could eventually be connected to your phone. Inert plasma gas generation is close to field ready if nitrogen generators can be miniaturized. Many of these components are already commercially available or at least have been reported in the literature. Comparisons to other “handheld” elemental analysis devices that employ XRF, LIBS, and electrochemical methods (and their limitations) demonstrate that a “cold” plasma-based spectrometer can be more than competitive. Migrating the cold plasma from an emission only source to a mass spectrometer source, would allow both analyte identification and potentially source apportionment through isotopic fingerprinting, and may be the last major hurdle to overcome. Finally, we offer a possible design to aid in making the cold plasma source more applicable to a field deployment.     

Resources and Methods for Engineering “Designer” Glycan-Binding Proteins

This review provides information on available methods for engineering glycan-binding proteins (GBP). Glycans are involved in a variety of physiological functions and are found in all domains of life and viruses. Due to their wide range of functions, GBPs have been developed with diagnostic, therapeutic, and biotechnological applications. The development of GBPs has traditionally been hindered by a lack of available glycan targets and sensitive and selective protein scaffolds; however, recent advances in glycobiology have largely overcome these challenges. Here we provide information on how to approach the design of novel “designer” GBPs, starting from the protein scaffold to the mutagenesis methods, selection, and characterization of the GBPs.     

Metabolite Profiling of “Green” Extracts of Cynara cardunculus subsp. scolymus,Cultivar “Carciofo di Paestum” PGI by 1H NMR and HRMS-Based Metabolomics

Globe artichoke (Cynara cardunculus L. var. scolymus L.), is a perennial plant widely cultivated in the Mediterranean area, known for its edible part named capitula or heads. Its functional properties are related to its high levels of polyphenolic compounds and inulin. “Carciofo di Paestum”, an Italian traditional cultivar, is a labeled PGI (Protected Geographical Indication) product of the Campania region, representing an important economic resource. So far, a few chemical investigations were performed on this cultivar, mainly focused on the analysis of methanol extracts. Due to the increasing use of food supplements, in this study, a comprehensive analysis of green extracts of “Carciofo di Paestum” PGI heads was performed. EtOH, EtOH: H₂O (80:20, 70:30, 60:40) extracts, as well as infusions and decoctions prepared according to Pharmacopeia XII were analyzed by LC-ESI/QExactive/MS/MS. A total of 17 compounds corresponding to caffeoylquinic acid derivatives, phenolics, flavonoids, and terpenoids were identified. The extracts were further submitted to NMR analysis to highlight the occurrence of primary metabolites. Both LCMS and NMR data were analyzed by Principal Component Analysis (PCA), showing significant differences among the extraction methods. Moreover, 5-caffeoylquinic acid and 1,5-dicaffeoylquinic acid were quantified in the extracts by LC-ESI/QTrap/MS/MS using the Multiple Reaction Monitoring (MRM) method. Furthermore, the phenolic content, antioxidant activity, and α-glucosidase inhibitory activity of C. cardunculus var. scolymus “Carciofo di Paestum” extracts were evaluated.     

Towards photoswitchable quadruple hydrogen bonds via a reversible “photolocking” strategy for photocontrolled self-assembly

Developing new photoswitchable noncovalent interaction motifs with controllable bonding affinity is crucial for the construction of photoresponsive supramolecular systems and materials. Here we describe a unique “photolocking” strategy for realizing photoswitchable control of quadruple hydrogen-bonding interactions on the basis of modifying the ureidopyrimidinone (UPy) module with an ortho-ester substituted azobenzene unit as the “photo-lock”. Upon light irradiation, the obtained Azo-UPy motif is capable of unlocking/locking the partial H-bonding sites of the UPy unit, leading to photoswitching between homo- and heteroquadruple hydrogen-bonded dimers, which has been further applied for the fabrication of novel tunable hydrogen bonded supramolecular systems. This “photolocking” strategy appears to be broadly applicable in the rational design and construction of other H-bonding motifs with sufficiently photoswitchable noncovalent interactions.

A photolocking strategy is described to achieve the construction of effectively photoswitchable quadruple hydrogen bonds featuring with photoregulable H-bonding affinities, which is further applied in the photocontrollable H-bonded self-assemblies.     

Rational design of an “all-in-one” phototheranostic

We report here porphodilactol derivatives and their corresponding metal complexes. These systems show promise as “all-in-one” phototheranostics and are predicated on a design strategy that involves controlling the relationship between intersystem crossing (ISC) and photothermal conversion efficiency following photoexcitation. The requisite balance was achieved by tuning the aromaticity of these porphyrinoid derivatives and forming complexes with one of two lanthanide cations, namely Gd³⁺ and Lu³⁺. The net result led to a metalloporphodilactol system, Gd-trans-2, with seemingly optimal ISC efficiency, photothermal conversion efficiency and fluorescence properties, as well as good chemical stability. Encapsulation of Gd-trans-2 within mesoporous silica nanoparticles (MSN) allowed its evaluation for tumour diagnosis and therapy. It was found to be effective as an “all-in-one” phototheranostic that allowed for NIR fluorescence/photoacoustic dual-modal imaging while providing an excellent combined PTT/PDT therapeutic efficacy in vitro and in vivo in 4T1-tumour-bearing mice.

We report here porphodilactol derivatives and their corresponding metal complexes as “all-in-one” phototheranostics by controlling the relationship between intersystem crossing (ISC) and photothermal conversion efficiency following photoexcitation.     

A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.