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A curious and noticeable structural feature in Schiff bases from 2-aminoaldoses is the fact that imino tautomers arranged equatorially in the most stable ring conformation exhibit a counterintuitive reverse anomeric effect (RAE) in the mutarotational equilibrium, i.e., the most stable and abundant anomer is the equatorial one (β). As shown by our very recent research, this effect arises from the total or partial inhibition of the exo-anomeric effect due to the presence of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen in the axial anomer (α). When the Schiff base adopts either an enamine structure or the imino group is protonated, the exo-anomeric effect is restored, and the axial α-anomer becomes the most stable species. Although the intramolecular H-bonding should appropriately be interpreted as a genuine stereoelectronic effect, the magnitude of the RAE could be affected by other structural parameters. Herein and through a comprehensive analysis of benzylidene, cinnamylidene, naphthalene, phenanthrene, and anthracene aldehydes, we show the robustness of the RAE effect, which is similar in extent to simple aldehydes screened so far, irrespective of the size and/or hydrophobicity of the substituent at the nitrogen atom.

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil's surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available. Routine in vitro diagnosis using the basophil activation test uses free amoxicillin, which is assumed to conjugate to a carrier present in blood. To standardize the methodology, we propose the use of well-controlled and defined nanomaterials functionalized with amoxicilloyl. Silica nanoparticles decorated with PAMAM-dendrimer-amoxicilloyl conjugates (NpDeAXO) of different sizes and amoxicilloyl densities (50-300 µmol amoxicilloyl/gram nanoparticle) have been prepared and chemically characterized. Two methods of synthesis were performed to ensure reproducibility and stability. Their functional effect on basophils was measured using an in-house basophil activation test (BAT) that determines CD63 + or CD203c high activation markers. It was observed that NpDeAXO nanocomposites are not only able to specifically activate basophils but also do so in a more effective way than free amoxicillin, pointing to a translational potential diagnosis.

Background: Obesity and its associated lifestyle are known risk factors for early-onset colorectal cancer and are associated with poor postoperative and survival outcomes in older patients. We aimed to investigate the impact of obesity on the outcomes of early-onset colorectal cancers., Methods: Retrospective review of all patients undergoing primary resection of colon or rectal adenocarcinoma at our institution between 2015-2022. Patients who had palliative resections, resections performed at another institution, appendiceal tumors, and were underweight were excluded. The primary endpoint was survival according to the patient's body mass index: normal weight (18-24.9 kg/m 2 ), overweight (25-29.9 kg/m 2 ), and obesity (≥30 kg/m 2 ). Patient and tumor characteristics and survival were compared between the three groups., Results: A total of 279 patients aged <50 years with colorectal cancer were treated at our hospital; 120 were excluded from the analysis for the following reasons: main treatment or primary resection performed at another hospital (n = 97), no resection/palliative resection (n = 23), or body mass index <18 kg/m 2 (n = 2). Of these, 157 patients were included in the analysis; 61 (38.9%) were overweight and 45 (28.7%) had obesity. Except for a higher frequency of hypertension in the overweight (P = .062) and obese (P = .001) groups, no differences in patient or tumor characteristics were observed. Mean overall survival was 89 months with normal weight, 92 months with overweight, and 65 months with obesity (P = .032). Mean cancer-specific survival was 95 months with normal weight, 94 months with overweight, and 68 months with obesity (P = .018). No statistically significant difference in disease-free survival (75 vs 70 vs 59 months, P = .844) was seen., Conclusion: Individuals with early-onset colorectal cancer who are overweight or obese present with similar tumor characteristics and postoperative morbidity to patients with normal weight. However, obesity may have a detrimental impact on their survival. Addressing obesity as a modifiable risk factor might improve early-onset colorectal cancer prognosis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The reverse anomeric effect is usually associated with the equatorial preference of nitrogen substituents at the anomeric center. Once postulated as another anomeric effect with explanations ranging from electrostatic interactions to delocalization effects, it is now firmly considered to be essentially steric in nature. Through an extensive research on aryl imines from 2-amino-2-deoxyaldoses, spanning nearly two decades, we realized that such substances often show an anomalous anomeric behavior that cannot easily be rationalized on the basis of purely steric grounds. The apparent preference, or stabilization, of the β-anomer takes place to an extent that not only neutralizes but also overcomes the normal anomeric effect. Calculations indicate that there is no stereoelectronic effect opposing the anomeric effect, resulting from the repulsion between electron lone pairs on the imine nitrogen and the endocyclic oxygen. Such data and compelling structural evidence unravel why the exoanomeric effect is largely inhibited. We are now confident, as witnessed by 2-iminoaldoses, that elimination of the exo-anomeric effect in the α-anomer is due to the formation of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen, thereby accounting for a true electronic effect. In addition, discrete solvation may help justify the observed preference for the β-anomer.

This paper explores and revisits in detail the formation and characterization of sugar-based aminonitriles, whose ultimate origin can be traced to the interaction of biomolecules with cyanide. Although the synthesis and spectroscopic data of 2-amino-aldononitriles were reported long ago, there are both contradictory and confusing results among the published data. We have now addressed this concern through an exhaustive structural elucidation of acylated 2-amino- and 2-alkyl(aryl)amino-2-deoxyaldonitriles using mass spectrometry and FT-IR, FT-Raman, and NMR spectroscopies. Several structures could be unambiguously determined through single-crystal X-ray diffraction, which allowed us to correct other misassignments. Moreover, this study unveils how steric and electronic effects influence the acylation outcome of the amino, (alkyl, aryl)amino, or acetamido group at C-2. The chirality at the latter, which was assigned tentatively through optical rotation correlation, and hence the preferential threo stereochemistry generated during the cyanohydrin synthesis of 2-amino-2-deoxy aldononitriles have now been established with confidence.

The persistence in the environment and possible harmful effects of neonicotinoid insecticides have raised some concerns, which have led to the proposal of various measures for their remediation. The aim of this work was to study the elimination of five neonicotinoids (thiamethoxam (THM), imidacloprid (IMI), clothianidin (CLO), thiacloprid (THC), and acetamiprid (ACE)) using ferrate (Fe(VI)) as the oxidizing agent. Firstly, second-order rate constants for the reactions of neonicotinoids with Fe(VI) were determined at different pHs. The most reactive compound was THC, with a rate constant of 400 ± 43 M -1  s -1 at pH 8 (the optimum pH considering the predominance of the most reactive species (HFeO 4 - ) and the decreasing self-decomposition of Fe(VI) with pH), followed by CLO (10.7 ± 1.7 M -1  s -1 ), THM (9.7 ± 0.7 M -1  s -1 ), and IMI (2.5 ± 0.6 M -1  s -1 ). ACE did not significantly react with Fe(VI). The oxidation of the selected pollutants in secondary effluents by Fe(VI) was rather slow, and only THC could be efficiently removed. The presence of natural organic matter (NOM) exerted a negative influence on the removal of the neonicotinoids of moderate reactivity with Fe(VI) (CLO, THM, and IMI). The additional presence of peroxymonosulfate (Fe(VI)/PMS system) slightly increased the removal of neonicotinoids due to the formation of hydroxyl and sulfate radicals. Finally, the application of the Fe(VI)/sulfite system considerably increased the oxidation rate of the selected pollutants, with enhanced formation of hydroxyl and, especially, sulfate radicals. Overall, these results suggest that the Fe(VI)/sulfite system has significant potential to address environmental and health concerns associated with neonicotinoids in water sources with low NOM content., (© 2024. The Author(s).)

A family of acylhydrazones have been prepared and characterized with the aim of investigating their potential as information storage systems. Their well-established synthetic methodologies allowed for the preparation of seven chemically stable acylhydrazones in excellent yields that have been photophysically and photochemically characterized. In addition, DFT and TD-DFT calculations have been performed to gain more insights into the structural, energetic and photophysical properties of the E / Z isomers. Our results reveal that E / Z configurational isomerization upon irradiation is highly dependent on the stabilization of the E or Z isomers due to the formation of intramolecular H bonds and the electronic/steric effects intrinsically related to their structures. In addition, Raman spectroscopy is also used to confirm the molecular structural changes after the formation of hydrogen bonds in the isomers.

This paper thoroughly explores the formation of Schiff bases derived from salicylaldehydes and a conformationally restricted amino alcohol (1-amino-2-indanol), as well as the generation of 1,3-oxazolidines, a key heterocyclic core present in numerous bioactive compounds. We provide enough evidences, both experimental-including crystallographic analyses and DFT-based calculations on imine/enamine tautomerism in the solid state and solution. In the course of imine formation, a pentacyclic oxazolidine-oxazine structure could be isolated with complete stereocontrol, whose configuration has been determined by merging theory and experiment. Mechanistic studies reveal that, although oxazolidines can be obtained under kinetic conditions, the prevalence of imines obeys to thermodynamic control as they are the most stable structures. The stereochemical outcome of imine cyclization under acylating conditions leads to formation of 2,4- trans -oxazolidines.

Polyhydroxylated phenols are components of biomass and precursors of pigments in plants. This paper reports a novel entry to xanthene dyes, involving the reaction of 2,4,6-trihydroxybenzaldehyde with primary aliphatic amines. This catalyst-free synthesis exhibits a high atom economy and can be conducted under eco-friendly conditions and operational simplicity.

Objective: The purpose of this study was to determine the impact of varying inflation parameters on paclitaxel delivery and retention using a commercially available DCB., Background: Drug-coated balloons (DCB) have become the standard treatment for peripheral artery disease. Clinical data suggest that varying DCB delivery parameters directly impact patient outcome. Differences in delivery parameters can potentially alter the retention of the drug coating on DCBs., Methods: Harvested porcine carotid arteries were utilized in an ex vivo pulsatile flow bioreactor system. The DCBs were then deployed at a DCB-to-artery ratio of 1:1 or 1.25:1, an inflation time of 30 seconds or 1 minute and transit time of 30 seconds or 3 minutes. The amount of drug retention in arterial tissue was evaluated by pharmacokinetic analysis at 1 hour and 1 day post DCB deployment., Results: Arterial paclitaxel levels were found to be less at an inflation ratio of 1:1 with 3-minute transit time as compared to 30 seconds of transit time at 1 hour (12.3 ± 1.6 ng/mg vs. 391 ± 139 ng/mg, P = .036). At 1-day, DCBs deployed at a ratio of 1:1 resulted in less drug retention as compared to 1.25:1 (61.3 ± 23.1 ng/mg vs. 404 ± 195 ng/mg, P = .013)., Conclusion: Arterial paclitaxel retention is reduced with extended transit times and sub-optimal expansion of the balloon. Optimization of delivery parameters can serve as an effective strategy to enhance clinical DCB outcomes.

The purpose of this pilot study was to investigate the feasibility of a perfusion catheter to deliver liquid paclitaxel into arterial segments. A clinically relevant rabbit ilio-femoral injury model was utilized to determine the impact of liquid paclitaxel delivered locally into the vessel wall using a perfusion catheter at 1 h to 14 days. Treatment by two clinically available forms of liquid paclitaxel, a solvent-based (sb) versus an albumin-bound (nab), along with a control (uncoated balloons), were investigated. Pharmacokinetic results demonstrated an increase in the retention of the sb-paclitaxel versus the nab-paclitaxel at 1 h; however, no other differences were observed at days one, three, and seven. Histological findings at 14 days showed significantly less neointimal area in the sb-paclitaxel treated arteries as compared with the nab-paclitaxel and the uncoated balloon-treated arteries. Additionally, percent area stenosis was significantly less in the sb-paclitaxel group. These results support the concept of local liquid delivery of paclitaxel into the arterial segments.

Imine and enamine bonds decorate the skeleton of numerous reagents, catalysts, and organic materials. However, it is difficult to isolate at will a single tautomer, as dynamic equilibria occur easily, even in the solid state, and are sensitive to electronic and steric effect, including π-conjugation and H-bonding. Here, using as model Schiff bases generated from salicylaldehydes and TRIS in a set of linear free energy relationships (LFER), we disclose how the formation of either imines or enamines can be controlled and provide a comprehensive framework that captures the structural underpinning of this prediction. This work highlights the potentiality of tailor-made designs en route to compounds with desirable functionality.

A one-pot procedure for preparing a series of chiral imines by direct condensation of d-glucamine with 2-hydroxyacetophenones is described. Under conventional acetylation an unexpected mixture of two different peracetylated molecules is obtained, one with an open enamine structure, and the other incorporating an N-acetyl-1,3-oxazolidine into the acyclic skeleton. Surprisingly, both molecules coexist within the crystal's unit cell, as inferred from single-crystal X-ray analysis of a 5-bromo-substituted aryl derivative. Moreover, the 1,3-oxazolidine ring exists as rotational conformers (E,Z) owing to the restricted rotation around the N-acetyl bond. The equilibrium involving imine and enamine structures has been assessed in detail, providing in addition linear free-energy relationships between the tautomerization constants (K T ) and the electronic effect of the substituents.

Tautomerism plays a pivotal role in structural stabilization and reactivity. Herein we investigate in detail, aided by DFT simulations, the case of gossypol, a naturally occurring atropisomeric dialdehyde showing promising properties as a male contraceptive and an antineoplasic agent. Its toxicity linked to reactive aldehydo groups can be reduced through amino conjugation. The occurrence of either imino or enamino structures is puzzling indeed and a clear-cut rationale is missing yet. N-enamine-N-enamine structures are prevalent or exclusive tautomers for Schiff bases from gossypol, while their corresponding hydrazones only possess N-imine-N-imine structures both in solution and the solid state. The modification of interactions between the lone pairs on the nitrogen atoms by altering the steric hindrance of the non-iminic nitrogen can favor enamine tautomers. This assumption has now been confirmed and, in the solid state, hydrazones from N-aminopiperidine and their cis-2,6-dimethylderivative present bis-imine and bis-enamine structures, respectively. In solution, these compounds exist in equilibrium between both structures. The tautomerization mechanism, analysis of axial chirality and aromaticity in such H-bonded pseudorings are discussed as well.

Refractive error (RE), particularly myopia, is the first cause of visual impairment throughout the world. This study aimed to depict the prevalence of myopia in a multicentric series of French individuals.This cross-sectional analysis was carried out between January 2012 and November 2013 in eye clinics dedicated to REs. Data collection included age, gender, best-corrected visual acuity, RE, and any relevant medical history involving laser refractive surgery and cataract surgery. Exclusion criteria consisted of monophthalm patients or those with incomplete demographic data.Prevalences in the overall population, by gender and by age groups were reported for mild myopia (-0.50 to -2.75 diopter [D]), moderate myopia (-3 to -5.75 D), high myopia (less than -6 D), and very high myopia (less than -10 D).The analysis included 100,429 individuals, mean age 38.5 years (± 16.9). Overall prevalence of myopia was 39.1% (95% CI 38.8-39.4). Prevalences of mild, moderate, high and very high myopia were respectively 25.1% (95% CI 25.4-24.9), 10.6% (95% CI 10.4-10.8), 3.4% (95% CI 3.3-3.5) and 0.5% (95% CI 0.48-0.57).Even if possible bias occurred in recruitment, our results are similar to RE data collected in nationally representative samples of Caucasians in other studies. This is to our knowledge, one of the largest European series of individuals dedicated to myopia prevalences in different age groups. These results confirm the importance of myopia as a major health issue in Western countries.

Purpose: Age-related macular degeneration (AMD) is the main cause of visual loss in the elderly population. With the use of anti-vascular endothelial growth factor, the visual outcomes of exudative AMD patients have been improved. This study was aimed at assessing the quality of life (QoL) of exudative AMD patients treated with ranibizumab and at determining its drivers in a real-life setting., Methods: We performed a national, cross-sectional, observational survey based on questionnaires sent to members of French associations relative to AMD between December 2012 and March 2013. Patients suffering from exudative AMD with at least one intravitreal injection of ranibizumab within the last 6 months were included. Demographics, AMD characteristics, visual acuity (VA) and past and ongoing treatments were collected. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was self-administered. A multivariate model was used to identify QoL drivers., Results: 416 questionnaires fulfilled the complete criteria for both QoL and cost analyses. The mean age of exudative AMD patients was 78.0 years and bilateral involvement was reported in 60.4%. The overall mean QoL score was 53.4. Mental health, driving and role difficulties were the most widely affected domains. After bivariate analyses, long-term illness status, worse VA and higher number of unpaid aids were associated with worse QoL, with odds ratios of 2.4, 5.2 and 11.6, respectively. The mean cost per year and per patient was 1,741 EUR. The main components of costs were aids and services and the purchase of visual equipment., Conclusions: The main predictors of QoL in exudative AMD patients treated with ranibizumab are VA outcomes, home healthcare and social services provided to the patients., (© 2015 S. Karger AG, Basel.)

Research at the interface between chemistry and cybernetics has led to reports of 'programmable molecules', but what does it mean to say 'we programmed a set of solution-phase molecules to do X'? A survey of recently implemented solution-phase circuitry indicates that this statement could be replaced with 'we pre-mixed a set of molecules to do X and functional subsets of X'. These hard-wired mixtures are then exposed to a set of molecular inputs, which can be interpreted as being keyed to human moves in a game, or as assertions of logical propositions. In nucleic acids-based systems, stemming from DNA computation, these inputs can be seen as generic oligonucleotides. Here, we report using reconfigurable nucleic acid catalyst-based units to build a multipurpose reprogrammable molecular automaton that goes beyond single-purpose 'hard-wired' molecular automata. The automaton covers all possible responses to two consecutive sets of four inputs (such as four first and four second moves for a generic set of trivial two-player two-move games). This is a model system for more general molecular field programmable gate array (FPGA)-like devices that can be programmed by example, which means that the operator need not have any knowledge of molecular computing methods.