Federica Balzano

Enantiodiscrimination by NMR Spectroscopy

The analysis of enantiorecognition processes involves the detection of enantiomeric species as well as the study of chiral discrimination mechanisms. In both fields Nuclear Magnetic Resonance (NMR) spectroscopy plays a fundamental role, providing several tools, based on the use of suitable chiral auxiliaries, for observing distinct signals of enantiomers and for investigating the complexation phenomena involved in enantiodiscrimination processes.

Improved synthesis of quaternary ammonium-chitosan conjugates (N+-Ch) for enhanced intestinal drug permeation

The pH-induced structural modifications of the reaction product between chitosan and 2-diethylaminoethyl chloride are studied with the purpose of testing and comparing the resulting chitosan derivatives on the basis of their intestinal drug permeability-enhancing properties. The reaction reproducibly yielded conjugates comprising short pendant chains of n adjacent diethyl-dimethylene-ammonium groups substituted onto the primary amino group of the chitosan repeating unit. The more significant derivatives, N(+)-Ch-7 (degree of substitution, DS=41%; n=3) and N(+)-Ch-8 (DS=59%; n=1.7) were prepared at pH 7 and 8, respectively. The apparent permeability (P(app)) of excised rat intestine was determined by means of Ussing type chambers. The hydrophilic fluorescein sodium (NaFlu) and fluorescein isothiocyanate dextran (MW 4400 Da) (FD-4), and the lipophilic rhodamine 123 (Rh-123), were applied in Ringer buffer to the apical side. Apical to basolateral transport was measured in the absence or presence of 0.5% (w/v) of the polymer under test. N(+)-Ch-7 and N(+)-Ch-8 were more effective P(app) enhancers than N-trimethyl-chitosan. Both N(+)-Ch-7 and N(+)-Ch-8 enhanced the P(app) of NaFlu (enhancement ratio, ER=1.84 and 1.33, respectively), while N(+)-Ch-8 was the more effective enhancer for FD-4 (ER=2.14). The P(app) of Rh-123 was significantly enhanced only by N(+)-Ch-7 (ER=1.37). Permeant-polymer binding counteracted the enhancement effect of polymer on transmembrane permeant flux. Contact with the chitosan conjugates did not impair the mucosal epithelium integrity.

Synergistic interaction between TS-polysaccharide and hyaluronic acid: implications in the formulation of eye drops.

An interaction between tamarind seed polysaccharide (TSP) and hyaluronic acid (HA) in aqueous solution has been ascertained. Various TSP/HA mixtures have been studied as the basis for the development of a potential excipient for eye drops synergistically improved over those of the separate polymers. Information about the nature of interpolymer interactions, and their dependence on TSP/HA ratios were obtained by NMR spectroscopy in solution. Superior mucin affinity of TSP/HA mixtures with respect to the single polysaccharides was assessed by NMR proton selective relaxation rate measurements. The mucoadhesivity of the TSP/HA (3/2) mixture, evaluated in vitro by NMR or viscometry, and in vivo by its mean and maximum residence time in rabbit precorneal area, is stronger than that of the component polysaccharides or the TSP/HA mixtures of different composition. TSP/HA (3/2) is little viscous and well tolerated by rabbit eyes. It stabilizes the tear film, thereby prolonging the residence of ketotifen fumarate and diclofenac sodium in tear fluid, but is unable to permeabilize the cornea. In conclusion, mucoadhesivity is responsible for the TSP/HA (3/2) synergistic enhancement of either extra- or intra-ocular drug bioavailability.

Nuclear magnetic resonance approaches to the rationalization of chromatographic enantiorecognition processes

NMR spectroscopy represents a valuable tool for obtaining information about structure and dynamics at a molecular level on the diastereoisomeric complexes formed by enantiomeric substrates and chromatographic chiral selectors or modifiers. Some examples collected from the literature show the potentialities of solution NMR spectroscopy in the rationalization of chromatographic enantiorecognition processes and the different NMR approaches needed according to the chiral selector features.

Versatile chiral auxiliaries for NMR spectroscopy based on carbamoyl derivatives of dihydroquinine

Abstract Carbamoylation at the C(9) site of dihydroquinine affords new and efficient chiral solvating agents for the NMR enantiodiscrimination of simple derivatives of chiral alcohols, amines, carboxyl acids and amino acids.

Multiscale morphology design of hybrid halide perovskites through a polymeric template

Hybrid halide perovskites have emerged as promising active constituents of next generation solution processable optoelectronic devices. During their assembling process, perovskite components undergo very complex dynamic equilibria starting in solution and progressing throughout film formation. Finding a methodology to control and affect these equilibria, responsible for the unique morphological diversity observed in perovskite films, constitutes a fundamental step towards a reproducible material processability. Here we propose the exploitation of polymer matrices as cooperative assembling components of novel perovskite CH3NH3PbI3 : polymer composites, in which the control of the chemical interactions in solution allows a predictable tuning of the final film morphology. We reveal that the nature of the interactions between perovskite precursors and polymer functional groups, probed by Nuclear Magnetic Resonance (NMR) spectroscopy and Dynamic Light Scattering (DLS) techniques, allows the control of aggregates in solution whose characteristics are strictly maintained in the solid film, and permits the formation of nanostructures that are inaccessible to conventional perovskite depositions. These results demonstrate how the fundamental chemistry of perovskite precursors in solution has a paramount influence on controlling and monitoring the final morphology of CH3NH3PbI3 (MAPbI3) thin films, foreseeing the possibility of designing perovskite : polymer composites targeting diverse optoelectronic applications.

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 (CILs) 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.

A conformational model of per-O-acetyl-cyclomaltoheptaose (-β-cyclodextrin) in solution: detection of partial inversion of glucopyranose units by NMR spectroscopy

The stereochemical features of per-O-acetyl-cyclomaltoheptaose (-beta-cyclodextrin) have been investigated in solution by NMR spectroscopy, and the deviation of functionalised glucopyranose rings from 4C(1) chairs to skew-type conformations has been detected.

NMR investigation of the interaction of (+)‐ and (−)‐flurbiprofen with β‐cyclodextrin

The sodium salts of (+)-(S)- and (−)-(R)-2-(2-fluoro-4-biphenylyl)propionic acid (flurbiprofen, FBP) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) having different association constants. Proton selective relaxation rate measurements revealed the existence of superior aggregated forms for both complexes (+)-FBP/β-CD and (−)-FBP/β-CD; information about their stereochemistry has been obtained by 2D ROESY analysis.

C11 versus C9 carbamoylation of quinine: a new class of versatile polyfunctional chiral solvating agents

Carbamoyl derivatives of quinine obtained by derivatization of its double bond have been prepared and used as chiral solvating agents for NMR spectroscopy: their efficiency reproduces very well that of quinine and its C9 carbamates in enantiodiscriminating underivatized and derivatized chiral substrates, respectively.