IR ion spectroscopy in a combined approach with MS/MS and IM-MS to discriminate epimeric anthocyanin glycosides (cyanidin 3-O-glucoside and -galactoside)

Anthocyanins are widespread in plants and flowers, being responsible for their different colouring. Two representative members of this family have been selected, cyanidin 3-O-β-glucopyranoside and 3-O-β-galactopyranoside, and probed by mass spectrometry based methods, testing their performance in discriminating between the two epimers. The native anthocyanins, delivered into the gas phase by electrospray ionization, display a comparable drift time in ion mobility mass spectrometry (IM-MS) and a common fragment, corresponding to loss of the sugar moiety, in their collision induced dissociation (CID) pattern. However, the IR multiple photon dissociation (IRMPD) spectra in the fingerprint range show a feature particularly evident in the case of the glucoside. This signature is used to identify the presence of cyanidin 3-O-β-glucopyranoside in a natural extract of pomegranate. In an effort to increase any differentiation between the two epimers, aluminum complexes were prepared and sampled for elemental composition by FT-ICR-MS. CID experiments now display an extensive fragmentation pattern, showing few product ions peculiar to each species. More noteworthy is the IRMPD behavior in the OH stretching range showing significant differences in the spectra of the two epimers. DFT calculations allow to interpret the observed distinct bands due to a varied network of hydrogen bonding and relative conformer stability

A comparative study of electrochemical, spectroscopic and structural properties of phenyl, thienyl and furyl substituted ethylenes

a detailed electrochemical and photophysical comparative study of three parallel series of phenyl, thienyl and furyl substituted ethylenes has been carried out, implemented by the computational calculation of selected terms. Relationships have been highlighted between molecular structure (number and type of aromatic rings) and important functional properties (in particular, electronic features and oligomerization ability). Interestingly, some of the studied heteroaryl-ethylenes show emission in the solid state displaying an aggregation-induced emission behavior

Intrinsic and Extrinsic Heavy-Atom Effects on the Multifaceted Emissive Behavior of Cyclic Triimidazole

Considering that heavy halogen atoms can be used to tune the emissive properties of organic luminogens, the understanding of their role in photophysics is fundamental for materials engineering. Here, the extrinsic and intrinsic heavy-atom effects on the photophysics of organic crystals were separately evaluated by comparing cyclic triimidazole (TT) with its monoiodo derivative (TTI) and its co-crystal with diiodotetrafluorobenzene (TTCo). Crystals of TT showed room-temperature ultralong phosphorescence (RTUP) originated from H-aggregation. TTI and TTCo displayed two additional long-lived components, the origin of which is elucidated through single-crystal X-ray and DFT/TDDFT studies. The results highlight the different effects of the I atom on the three phosphorescent emissions. Intrinsic heavy-atom effects play a major role on molecular phosphorescence, which is displayed at room temperature only for TTI. The H-aggregate RTUP and the I c5 c5 c5N XB-induced (XB=halogen bond) phosphorescence on the other side depend only on packing features

Long-living optical gain induced by solvent viscosity in a push-pull molecule

The combination of continuum and ultrafast pump-probe spectroscopy with DFT and TDDFT calculations, in viscous and non-viscous environments, is effective in unraveling important features of the twisted intramolecular charge transfer mechanism in a new push-pull molecule that possesses aggregation induced emission properties. Long-living optical gain is found when this mechanism is inhibited, highlighting the importance of the environment rigidity in the design of materials for photonic applications

Mechanisms of immune evasion in multiple myeloma: Open questions and therapeutic opportunities

Multiple myeloma (MM) is the second most common hematologic malignancy, charac-terized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immuno-suppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

Combined lymphocyte/monocyte count, D-dimer and iron status predict COVID-19 course and outcome in a long-term care facility

Background: The Sars-CoV-2 can cause severe pneumonia with multiorgan disease; thus, the identification of clinical and laboratory predictors of the progression towards severe and fatal forms of this illness is needed. Here, we retrospectively evaluated and integrated laboratory parameters of 45 elderly subjects from a long-term care facility with Sars-CoV-2 outbreak and spread, to identify potential common patterns of systemic response able to better stratify patients’ clinical course and outcome. Methods: Baseline white blood cells, granulocytes’, lymphocytes’, and platelets’ counts, hemoglobin, total iron, ferritin, D-dimer, and interleukin-6 concentration were used to generate a principal component analysis. Statistical analysis was performed by using R statistical package version 4.0. Results: We identified 3 laboratory patterns of response, renamed as low-risk, intermediate-risk, and high-risk, strongly associated with patients’ survival (p < 0.01). D-dimer, iron status, lymphocyte/monocyte count represented the main markers discriminating high- and low-risk groups. Patients belonging to the high-risk group presented a significantly longer time to ferritin decrease (p: 0.047). Iron-to-ferritin-ratio (IFR) significantly segregated recovered and dead patients in the intermediate-risk group (p: 0.012). Conclusions: Our data suggest that a combination of few laboratory parameters, i.e. iron status, D-dimer and lymphocyte/monocyte count at admission and during the hospital stay, can predict clinical progression in COVID-19