110 research outputs found
The Phenomenon of Self-Induced Diastereomeric Anisochrony and Its Implications in NMR Spectroscopy
Nuclear magnetic resonance (NMR) spectroscopy is an analytical technique largely applied in the analysis of discrimination processes involving enantiomeric substrates and chiral agents, which can interact with the analyte either via covalent bonding or via formation of diastereomeric solvates. However, enantiodiscrimination has been observed, in some cases, even in the absence of any additional chiral selector. The reasons behind this phenomenon must be found in the capability of some chiral substrates to interact with themselves by forming diastereomeric solvates in solution that can generate nonequivalences in the NMR spectra of enantiomerically enriched mixtures. As a result, differentiation of enantiomers is observed, thus allowing the quantification of the enantiomeric composition of the mixture under investigation. The tendency of certain substrates to self-aggregate and to generate diastereomeric adducts in solution can be defined as Self-Induced Diastereomeric Anisochrony (SIDA), but other acronyms have been used to refer to this phenomenon. In the present work, an overview of SIDA processes investigated via NMR spectroscopy will be provided, with a particular emphasis on the nature of the substrates involved, on the interaction mechanisms at the basis of the phenomenon, and on theoretical treatments proposed in the literature to explain them
Role of nanostructured aggregation of chitosan derivatives on [5-methionine]enkephalin affinity
Affinities of quaternary ammonium-chitosan conjugates, their thiolated derivatives and corresponding nanostructured aggregates towards the hydrophilic drug [5-methionine]enkephalin were compared by Nuclear Magnetic Resonance (NMR) spectroscopic methods based on proton selective relaxation rate measurements. Nanoaggregates showed enhanced drug affinity in comparison with corresponding polymers, especially in the case of thiolated systems
Regio- and stereoselective behavior of l-arabinal-derived vinyl epoxide in nucleophilic addition reactions. Comparison with conformationally restricted d-galactal-derived analogs
Abstract The regio- and stereoselectivity of the addition reactions of O-, C-, N-, and S-nucleophiles to l-arabinal-derived vinyl epoxide 2, the simplest non-conformationally restricted glycal-derived vinyl epoxide, has been examined and compared with the corresponding, conformationally restricted d-galactal-derived analogs 1β and 1β-Me. Results indicated that the 1,4-/1,2-regioselectivity ratio and the related syn-1,4-/anti-1,2-stereoselectivity observed in glycal-derived vinyl oxiranes is independent of the presence of substituents on the six-membered unsaturated ring, and the absence of conformational freedom: it depends only on the ability of the nucleophile to give a coordination process with the oxirane oxygen in the form of a hydrogen bond or through a coordinating cation
A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone
The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices
Efficient Ligand Passivation Enables Ultrastable CsPbX3 Perovskite Nanocrystals in Fully Alcohol Environments
Halide perovskite nanocrystals (PNCs) have demonstrated their wide potential to fabricate efficient optoelectronic devices and to prepare promising photocatalysts for solar-driven photo(electro)chemical reactions. However, their use in most of the practical applications is limited due to the instability of PNCs in polar environments. Here, the preparation of non-encapsulated CsPbX3 nanocrystals dispersed in fully alcohol environments, with outstanding stability through surface defect passivation strategy is reported. By using didodecyldimethylammonium bromide (DDAB) during material post-treatment, highly luminescent CsPbBr3 PNCs with remarkable stability in methanol/butanol medium up to 7 months with near-unity photoluminescence quantum yield are achieved. This approach is extrapolated to stabilize iodine-based CsPbBr3-xIx and CsPbI3 PNCs, showing an improvement of their photoluminescence features and stability in these high polar alcohols up to 6 h. DDAB mediates the defect suppression through ligand exchange and avoids the full permeation of alcohol to be in contact with the PNCs. In this context, DDAB induces ionization of alcohol molecules to strengthen the surface passivation. The findings open the door to the development of long-term stable CsPbX3 PNCs with high optical performance to be used in polar environments.This work was supported by the European Innovation Council (EIC) via OHPERA project (grant agreement 101071010), the Spanish Ministry of Science and Innovation under projects STABLE (PID2019-107314RB-I00) and ECOCAT (PID2020-116093RB-C41), the Spanish Ministry of Science and Innovation under project She-LED (PID2021-122960OA-I00), and the Generalitat Valenciana via Prometeo Grant Q-Solutions (CIPROM/2021/078). C.A.M. acknowledges APOSTD grant (APOSTD/2021/251) for funding. The authors also thank the Ministry of Education, Youth and Sports of the Czech Republic for the financial support of XPS measurements using CEMNAT infrastructure (project LM 2018103). The authors are very grateful to the “Serveis Centrals d'Instrumentació Científica (SCIC)” of the Universitat Jaume I
Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors
Hedgehog signaling is essential for tissue development and stemness, and its deregulation has been observed in many tumors. Aberrant activation of Hedgehog signaling is the result of genetic mutations of pathway components or other Smo-dependent or independent mechanisms, all triggering the downstream effector Gli1. For this reason, understanding the poorly elucidated mechanism of Gli1-mediated transcription allows to identify novel molecules blocking the pathway at a downstream level, representing a critical goal in tumor biology. Here, we clarify the structural requirements of the pathway effector Gli1 for binding to DNA and identify Glabrescione B as the first small molecule binding to Gli1 zinc finger and impairing Gli1 activity by interfering with its interaction with DNA. Remarkably, as a consequence of its robust inhibitory effect on Gli1 activity, Glabrescione B inhibited the growth of Hedgehog-dependent tumor cells in vitro and in vivo as well as the self-renewal ability and clonogenicity of tumor-derived stem cells. The identification of the structural requirements of Gli1/DNA interaction highlights their relevance for pharmacologic interference of Gli signaling
New Platinum(II) Complexes Containing Chiral Secondary Amines: Efficient and Versatile Chiral Derivatizing Agents for the Determination of the Enantiomeric Composition and Absolute Configuration of Chiral Unsaturated Compounds by 195Pt NMR Spectroscopy
Chiral mono- and dicarbamates derived from ethyl (S)-lactate: convenient chiral solvating agents for the direct and efficient enantiodiscrimination of amino acid derivatives by 1H NMR spectroscopy
New lactate-based CSAs for 1H NMR enantiodifferentiation of amino acid derivatives
Chiral NMR solvating additives for differentiation of enantiomers
This chapter will describe the general features and main categories of chiral solvating agents (CSAs) for NMR spectroscopy, spanning from low-medium sized CSAs to macrocyclic ones. CSAs based on chiral ionic liquids will be introduced, in view of their increasing popularity, and, finally, a short paragraph will be dedicated to special applications of CSAs in particular experimental conditions. Several valuable works, which are mainly devoted to investigate enantiodifferentiation mechanisms by NMR, will not be discussed The main objective is to identify the current trend in the research areas dedicated to the development of new CSAs for NMR spectroscopy
New Chiral Solvating and Derivatizing Agents for the Enantiomeric Purities Determinations by NMR Spectroscopy
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