A Variational Approach to the Maximization of Preferences Without Numerical Representation

Journal of Optimization Theory and Applications - We introduce a variational approach to study a maximization problem of preferences that cannot be represented by a utility function. In such...     

Enantioselective analysis of venlafaxine and its active metabolites: A review on the separation methodologies

Venlafaxine (VFX) is a serotonin and norepinephrine reuptake inhibitor chiral drug used in therapy as an antidepressant in the form of a racemate consisting of R‐ and S‐VFX. The two enantiomers of VFX exhibit different pharmacological activities: R‐VFX inhibits both norepinephrine and serotonin synaptic reuptake, whereas S‐VFX inhibits only the serotonin one. R‐ and S‐VFX are metabolized in the liver to the respective R‐ and S‐O‐desmethylvenlafaxine (ODVFX), R‐ and S‐N‐desmethylvenlafaxine (NDVFX), and R‐ and S‐N,O‐didesmethylvenlafaxine (NODVFX). The pharmacological profile of ODVFX is close to that of VFX, whereas the other two chiral metabolites (NDVFX and NODVFX) have lower affinity for the receptor sites. The pharmacokinetics of the VFX enantiomers appear stereoselective, including the metabolism process. In the past 20 years, several studies describing the enantioselective analysis of R‐ and S‐VFX in pharmaceutical formulations and its chiral metabolites in biological matrices were published. These methods encompass liquid chromatography coupled with UV detection, mass spectrometry, or tandem mass spectrometry, and capillary electrophoresis. This paper reviews the published methods used for the determination of the individual enantiomers of VFX and its chiral metabolites in different matrices.     

Is it True That the Normal Valence‐Length Correlation Is Irrelevant for Metal–Metal Bonds?

The most intriguing feature of metal–metal bonds in inorganic compounds is an apparent lack of correlation between the bond order and the bond length. In this study, we combine a variety of literature data obtained by quantum chemistry and our results based on the empirical bond valence model (BVM), to confirm for the first time the existence of a normal exponential correlation between the effective bond order (EBO) and the length of the metal–metal bonds. The difference between the EBO and the formal bond order is attributed to steric conflict between the (TM)_n cluster (TM=transition metal) and its environment. This conflict, affected mainly by structural type, should cause high lattice strains, but electron redistribution around TM atoms, evident from the BVM calculations, results in a full or partial strain relaxation.     

A Novel [OSSO]-Type Chromium(III) Complex as a Versatile Catalyst for Copolymerization of Carbon Dioxide with Epoxides

A new chromium(III) complex, bearing a bis-thioether-diphenolate [OSSO]-type ligand, was found to be an efficient catalyst in the copolymerization of CO₂ and epoxides to achieve poly(propylene carbonate), poly(cyclohexene carbonate), poly(hexene carbonate) and poly(styrene carbonate), as well as poly(propylene carbonate)(cyclohexene carbonate) and poly(propylene carbonate)(hexene carbonate) terpolymers.     

On solutions to a FitzHugh–Rinzel type model

Ricerche di Matematica - A ternary autonomous dynamical system of FitzHugh–Rinzel type is analyzed. The system, at start, is reduced to a nonlinear integro differential equation. The...     

Anti-Cancer Effects of Carnosine—A Dipeptide Molecule

Background: Carnosine is a dipeptide molecule (β-alanyl-l-histidine) with anti-inflammatory, antioxidant, anti-glycation, and chelating properties. It is used in exercise physiology as a food supplement to increase performance; however, in vitro evidence suggests that carnosine may exhibit anti-cancer properties. Methods: In this study, we investigated the effect of carnosine on breast, ovarian, colon, and leukemic cancer cell proliferation. We further examined U937 promonocytic, human myeloid leukemia cell phenotype, gene expression, and cytokine secretion to determine if these are linked to carnosine’s anti-proliferative properties. Results: Carnosine (1) inhibits breast, ovarian, colon, and leukemic cancer cell proliferation; (2) upregulates expression of pro-inflammatory molecules; (3) modulates cytokine secretion; and (4) alters U937 differentiation and phenotype. Conclusion: These effects may have implications for a role for carnosine in anti-cancer therapy.     

Enantiomeric analysis of drugs in water samples by using liquid–liquid microextraction and nano-liquid chromatography

The nano-LC technique is increasingly used for both fast studies on enantiomeric analysis and test beds of novel stationary phases due to the small volumes involved and the short conditioning and analysis times. In this study, the enantioseparation of 10 drugs from different families was carried out by nano-LC, utilizing silica with immobilized amylose tris(3-chloro-5-methylphenylcarbamate) column. The effect on chiral separation caused by the addition of different salts to the mobile phase was evaluated. To simultaneously separate as many enantiomers as possible, the effect of buffer concentration in the mobile phase was studied, and, to increase the sensitivity, a liquid–liquid microextraction based on the use of isoamyl acetate as sustainable extraction solvent was applied to pre-concentrate four chiral drugs from tap and environmental waters, achieving satisfactory recoveries (>70%).     

The Crucial Role of Sb2F10 in the Chemical Synthesis of F2

The purely chemical synthesis of fluorine is a spectacular reaction which for more than a century had been believed to be impossible. In 1986, it was finally experimentally achieved, but since then this important reaction has not been further studied and its detailed mechanism had been a mystery. The known thermal stability of MnF₄ casts serious doubts on the originally proposed hypothesis that MnF₄ is thermodynamically unstable and decomposes spontaneously to a lower manganese fluoride and F₂. This apparent discrepancy has now been resolved experimentally and by electronic structure calculations. It is shown that the reductive elimination of F₂ requires a large excess of SbF₅ and occurs in the last reaction step when in the intermediate [SbF₆][MnF₂][Sb₂F₁₁] the addition of one more SbF₅ molecule to the [SbF₆]⁻ anion generates a second tridentate [Sb₂F₁₁]⁻ anion. The two tridentate [Sb₂F₁₁]⁻ anions then provide six fluorine bridges to the Mn atom thereby facilitating the reductive elimination of the two fluorine ligands as F₂.     

Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec-7

We investigated two recently synthesized and characterized sialyl derivatives, bearing the Neu5Ac-α-(2-6)-Gal epitope, as promising binders for Siglec-7, an inhibitory Siglec mainly found on natural killer cells. A variety of sialoglycan structures can be recognized by Siglec-7 with implications in the modulation of immune responses. Notably, overexpression of sialylated glycans recognized by Siglec-7 can be associated with the progression of several tumors, including melanoma and renal cell carcinoma. NOE-based NMR techniques, including Saturation Transfer Difference and transferred-NOESY NMR, together with molecular docking and dynamic simulations were combined to shed light on the molecular basis of Siglec-7 recognition of two conformationally constrained Sialyl-Tn antigen analogs. We, therefore, identify the ligands epitope mapping and their conformational features and propose 3D models accurately describing the protein-ligand complexes. We found that the binding site of Siglec-7 can accommodate both synthetic analogs, with the sialic acid mainly involved in the interaction. Moreover, the flexibility of Siglec-7 loops allows a preferred accommodation of the more rigid compound bearing a biphenyl moiety at position 9 of the sialic acid that contributed to the interaction to a large extent. Our findings provided insights for developing potential novel high affinity ligands for Siglec-7 to hinder tumor evasion.     

Direct On‐Surface Patterning of a Crystalline Laminar Covalent Organic Framework Synthesized at Room Temperature

We report herein an efficient, fast, and simple synthesis of an imine‐based covalent organic framework (COF) at room temperature (hereafter, RT‐COF‐1 ). RT‐COF‐1 shows a layered hexagonal structure exhibiting channels, is robust, and is porous to N₂ and CO₂. The room‐temperature synthesis has enabled us to fabricate and position low‐cost micro‐ and submicropatterns of RT‐COF‐1 on several surfaces, including solid SiO₂ substrates and flexible acetate paper, by using lithographically controlled wetting and conventional ink‐jet printing.