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Background: In the first part of our study on possible contribution of dispersion forces in liquid-phase enantioseparations, the enantioseparation of the axially chiral 3,3'-dibromo-5,5'-bis-ferrocenylethynyl-4,4'-bipyridine with an amylose tris(3,5-dimethylphenylcarbamate)-based chiral column appeared reasonably consistent with a picture of the enantioselective recognition based on the interplay between hydrogen bond (HB), π-π stacking and dispersion interactions., Results: In the second part of this study, we evaluated the impact of analyte and chiral stationary phase (CSP) structure, mobile phase and temperature on the enantioseparations of planar chiral 1-(iodoethynyl)-3-arylferrocenes (3-aryl = phenyl, 2-naphthyl, 4-methylphenyl, 4-t-butylphenyl) with polysaccharide-based chiral columns. The main aim of the present study was to understand the molecular bases of the high affinity observed for the second eluted (R p )-enantiomer of some of these analytes toward amylose phenylcarbamate-based selectors when methanol-containing mixtures were used as mobile phases. Significantly, higher affinity of the second eluted (R p )-enantiomer toward the selector could be also observed for the sterically hindered 1-(iodoethynyl)-3-(4-t-butylphenyl)ferrocene (k 2  = 6.21) compared to the smaller 1-(iodoethynyl)-3-(4-methylphenyl)ferrocenes (k 2  = 4.07) as 2.5% methanol was added to the n-hexane-based mobile phase., Significance: This study reasonably showed that the contribution of dispersion forces may explain the unusually large retention of the second eluted enantiomers observed for the enantioseparation of some planar chiral 1-(iodoethynyl)-3-arylferrocenes with amylose-based selectors. Based on the obtained results, we can conclude that in liquid-phase enantioseparation steric repulsion can be turned into attraction depending on the features of analyte, selector, and mobile phase., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ependymal cells form a specialized brain-cerebrospinal fluid (CSF) interface and regulate local CSF microcirculation. It is becoming increasingly recognized that ependymal cells assume a reactive state in response to aging and disease, including conditions involving hypoxia, hydrocephalus, neurodegeneration, and neuroinflammation. Yet what transcriptional signatures govern these reactive states and whether this reactivity shares any similarities with classical descriptions of glial reactivity (i.e., in astrocytes) remain largely unexplored. Using single-cell transcriptomics, we interrogated this phenomenon by directly comparing the reactive ependymal cell transcriptome to the reactive astrocyte transcriptome using a well-established model of autoimmune-mediated neuroinflammation (MOG 35-55 EAE). In doing so, we unveiled core glial reactivity-associated genes that defined the reactive ependymal cell and astrocyte response to MOG 35-55 EAE. Interestingly, known reactive astrocyte genes from other CNS injury/disease contexts were also up-regulated by MOG 35-55 EAE ependymal cells, suggesting that this state may be conserved in response to a variety of pathologies. We were also able to recapitulate features of the reactive ependymal cell state acutely using a classic neuroinflammatory cocktail (IFNγ/LPS) both in vitro and in vivo. Taken together, by comparing reactive ependymal cells and astrocytes, we identified a conserved signature underlying glial reactivity that was present in several neuroinflammatory contexts. Future work will explore the mechanisms driving ependymal reactivity and assess downstream functional consequences., (© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

The ability of triaryltelluronium salts to interact with N-halosuccinimides (NXS) through chalcogen bonding (ChB) in the solid state and in solution is demonstrated herein. Cocrystals of the triaryltelluronium bearing two CF 3 electron-withdrawing groups per aryl ring with N-chloro-, N-bromo- and N-iodosuccinimide (respectively NCS, NBS and NIS) were analyzed by X-ray diffraction, evidencing a ChB between tellurium and the carbonyl group of NXS. This ChB was confirmed in solution by NMR spectroscopy, especially by 125 Te NMR titration experiment, which allowed the determination of the association constant (K a ) between the telluronium and NBS. The so-obtained K a value of 17.3±0.6 M -1 indicated a moderate interaction in solution because of the competitive role of the solvent. The strength of the Te⋅⋅⋅O ChB was however sufficient enough to promote the catalytic halofunctionalization of aromatics and of alkenes such as the intra- and intermolecular haloalkoxylation and haloesterification of alkenes., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

In the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. However, although bound iodine atoms are considered powerful HaB donors, few iodinated new drugs were reported so far. Recently, iodinated 4,4'-bipyridines showed interesting properties as HaB donors in solution and in the solid state. In this paper, a study on the inhibition activity of seven halogenated 4,4'-bipyridines against malignant melanoma (MM) cell proliferation is described. Explorative dose/response proliferation assays were first performed with three 4,4'-bipyridines by using four MM cell lines and the normal BJ fibroblast cell line as control. Among them, the A375 MM cell line was the most sensitive, as determined by MTT assays, which was selected to evaluate the antiproliferative activity of all 4,4'-bipyridines. Significantly, the presence of an electrophilic iodine impacted the biological activity of the corresponding compounds. The 3,3',5,5'-tetrachloro-2-iodo-4,4'-bipyridine showed significant antiproliferation activity against the A375 cell line, and lower toxicity on BJ fibroblasts. Through in silico studies, the stereoelectronic features of possible sites determining the bioactivity were explored. These results pave the way for the utilization of iodinated 4,4'-bipyridines as templates to design new promising HaB-enabled inhibitors of MM cell proliferation., (© 2024 Wiley-VCH GmbH.)

Telluronium salts [Ar 2 MeTe]X were synthesized, and their Lewis acidic properties towards a number of Lewis bases were addressed in solution by physical and theoretical means. Structural X-ray diffraction analysis of 21 different salts revealed the electrophilicity of the Te centers in their interactions with anions. Telluroniums' propensity to form Lewis pairs was investigated with OPPh 3 . Diffusion-ordered NMR spectroscopy suggested that telluroniums can bind up to three OPPh 3 molecules. Isotherm titration calorimetry showed that the related heats of association in 1,2-dichloroethane depend on the electronic properties of the substituents of the aryl moiety and on the nature of the counterion. The enthalpies of first association of OPPh 3 span -0.5 to -5 kcal mol -1 . Study of the affinity of telluroniums for OPPh 3 by state-of-the-art DFT and ab-initio methods revealed the dominant Coulombic and dispersion interactions as well as an entropic effect favoring association in solution. Intermolecular orbital interactions between [Ar 2 MeTe] + cations and OPPh 3 are deemed insufficient on their own to ensure the cohesion of [Ar 2 MeTe ⋅ B n ] + complexes in solution (B=Lewis base). Comparison of Grimme's and Tkatchenko's DFT-D4/MBD-vdW thermodynamics of formation of higher [Ar 2 MeTe ⋅ B n ] + complexes revealed significant molecular size-dependent divergence of the two methodologies, with MBD yielding better agreement with experiment., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Chalcogen bonding (ChB) is the non-covalent interaction occurring between chalcogen atoms as Lewis acid sites and atoms or groups of atoms able to behave as Lewis bases through their lone pair or π electrons. Analogously to its sister halogen bonding, the high directionality of this interaction was implemented for precise structural organizations in the solid state and in solution. Regarding catalysis, ChB is now accepted as a new mode of activation as demonstrated by the increased number of examples in the last five years. In the family of ChB catalysts, those based on tellurium rapidly appeared to overcome their lighter sulfur and selenium counterparts. In this review, we highlight the Lewis acid properties of tellurium-based derivatives in solution and summarize the start-of-the-art of their applications in catalysis., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Highly ordered chiral secondary structures as well as multiple (tunable) recognition sites are the keys to success of polysaccharide carbamate-based chiral selectors in enantioseparation science. Hydrogen bonds (HBs), dipole-dipole, and π-π interactions are classically considered the most frequent noncovalent interactions underlying enantioselective recognition with these chiral selectors. Very recently, halogen, chalcogen and π-hole bonds were also identified as interactions working in polysaccharide carbamate-based selectors to promote enantiomer distinction. On the contrary, the function of dispersion interactions in this field was not explored so far., Results: The enantioseparation of chiral ferrocenes featuring chiral axis or chiral plane as stereogenic elements was performed by comparing five polysaccharide carbamate-based chiral columns, with the aim to identify enantioseparation outcomes that could be reasonably determined by dispersion forces, making available a reliable experimental data set for future theoretical studies to confirm the heuristic hypothesis. The effects of mobile phase polarity and temperature on the enantioseparation were considered, and potential recognition sites on analytes and selectors were evaluated by electrostatic potential (V) analysis and molecular dynamics (MD). In this first part, the enantioseparation of 3,3'-dibromo-5,5'-bis-ferrocenylethynyl-4,4'-bipyridine bearing two ferrocenylethynyl units linked to an axially chiral core was performed and compared to that of the analyte featuring the same structural motif with two phenyl groups in place of the ferrocenyl moieties. The results of this study showed the superiority of the ferrocenyl compared to the phenyl group, as a structural element favouring enantiodifferentiation., Significance and Novelty: Even if dispersion (London) forces have been envisaged acting in liquid-phase enantioseparations, focused studies to explore possible contributions of dispersion forces with polysaccharide carbamate-based selectors are practically missing. This study allowed us to collect experimental information that support the involvement of dispersion forces as contributors to liquid-phase enantioseparation, paving the way to a new picture in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In the field of noncovalent interactions, chalcogen bonding (ChB) involving the tellurium atom is currently attracting much attention in supramolecular chemistry and in catalysis. However, as a prerequisite for its application, the ChB should be studied in solution to assess its formation and, if possible, to evaluate its strength. In this context, new tellurium derivatives bearing CH 2 F and CF 3 groups were designed to exhibit Te⋯F ChB and were synthesized in good to high yields. In both types of compounds, Te⋯F interactions were characterized in solution by combining 19 F, 125 Te and HOESY NMR techniques. These Te⋯F ChBs were shown to contribute to the overall J Te-F coupling constants (94-170 Hz) measured in the CH 2 F- and CF 3 -based tellurium derivatives. Finally, a variable temperature NMR study allowed us to approximate the energy of the Te⋯F ChB, from 3 kJ mol -1 for the compounds with weak Te σ-holes to 11 kJ mol -1 for Te σ-holes activated by the presence of strong electron withdrawing substituents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In the chalcogen series, tellurium species exhibit the strongest chalcogen bonding (ChB) interaction with electron-rich atom. This property explains the renewed interested toward tellurium-based derivatives and their use in different applications, such as organocatalysis. In this context, the catalytic activity of telluronium salts in the Povarov reaction is presented herein. Different dienophiles, as well as imines of variable electronic nature, efficiently react in the presence of catalytic amount of either diarylmethyltelluronium or triaryltelluronium salts. Both catalysts could also readily perform the three-component Povarov reaction starting from aldehyde, aniline and dihydrofuran. The reactivity of telluroniums towards imines and aldehydes was confirmed in the solid state by the ability of Te atom to interact through ChB with the oxygen carbonyl of acetone, and in solution with significant shift variations of the imine proton and of the tellurium atom in 1 H and 125 Te NMR spectroscopy. For the most active telluronium catalysts bearing CF 3 groups, association constants (K) with N-phenyl phenylmethanimine in the range 22-38 M -1 were measured in dichloromethane., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Chalcogen bonds (ChBs) occur between molecules containing Lewis acidic chalcogen substituents and Lewis bases. Recently, ChB emerged as a pivotal interaction in solution-based applications such as anion recognition, anion transport and catalysis. However, before moving to applications, the involvement of ChB must be established in solution. In this Concept article, we provide a brief review of the currently available experimental investigations of ChB in solution., (© 2022 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

In this study, the enantioseparation of 14 planar chiral ferrocenes containing halogen atoms, and methyl, iodoethynyl, phenyl, and 2-naphthyl groups, as substituents, was explored with a cellulose tris(4-methylbenzoate) (CMB)-based chiral column under multimodal elution conditions. n-Hexane/2-propanol (2-PrOH) 95:5 v/v, pure methanol (MeOH), and MeOH/water 90:10 v/v were used as mobile phases (MPs). With CMB, baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.24 to 1.77, whereas only three analytes could be enantioseparated with 1.14 ≤ α ≤ 1.51 on a cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC)-based column, used as a reference for comparison, under the same elution conditions. Pendant group-dependent reversal of the enantiomer elution order was observed in several cases by changing CMB to CDMPC. The impact of analyte and chiral stationary phase (CSP) structure, and MP polarity on the enantioseparation, was evaluated. The two cellulose-based CSPs featured by different pendant groups were also compared in terms of thermodynamics. For this purpose, enthalpy (ΔΔH°), entropy (ΔΔS°) and free energy (ΔΔG°) differences, isoenantioselective temperatures (T iso ), and enthalpy/entropy ratios (Q), associated with the enantioseparations, were derived from van 't Hoff plots by using n-hexane/2-PrOH 95:5 v/v and methanol/water 90:10 v/v as MPs. With the aim to disclose the functions of the different substituents in mechanisms and noncovalent interactions underlying analyte-selector complex formation at molecular level, electrostatic potential (V) analysis and molecular dynamics simulations were used as computational techniques. On this basis, enantioseparations and related mechanisms were investigated by integrating theoretical and experimental data., (© 2022 Wiley-VCH GmbH.)

In the last decade, planar chiral ferrocenes have attracted a growing interest in several fields, particularly in asymmetric catalysis, medicinal chemistry, chiroptical spectroscopy and electrochemistry. In this frame, the access to pure or enriched enantiomers of planar chiral ferrocenes has become essential, relying on the availability of efficient asymmetric synthesis procedures and enantioseparation methods. Despite this, in enantioseparation science, these metallocenes were not comprehensively explored, and very few systematic analytical studies were reported in this field so far. On the other hand, enantioselective high-performance liquid chromatography has been frequently used by organic and organometallic chemists in order to measure the enantiomeric purity of planar chiral ferrocenes prepared by asymmetric synthesis. On these bases, this review aims to provide the reader with a comprehensive overview on the enantioseparation of planar chiral ferrocenes by discussing liquid-phase enantioseparation methods developed over time, integrating this main topic with the most relevant aspects of ferrocene chemistry. Thus, the main structural features of ferrocenes and the methods to model this class of metallocenes will be briefly summarized. In addition, planar chiral ferrocenes of applicative interest as well as the limits of asymmetric synthesis for the preparation of some classes of planar chiral ferrocenes will also be discussed with the aim to orient analytical scientists towards 'hot topics' and issues which are still open for accessing enantiomers of ferrocenes featured by planar chirality., (© 2022 The Authors. Electrophoresis published by Wiley-VCH GmbH.)

The σ-hole interaction represents a noncovalent interaction between atoms with σ-hole(s) on their surface (such as halogens and chalcogens) and negative sites. Over the last decade, significant developments have emerged in applications where the σ-hole interaction was demonstrated to play a key role in the control over chirality. The aim of this review is to give a comprehensive overview of the current advancements in the use of σ-hole interactions in stereoselective processes, such as formation of chiral supramolecular assemblies, separation of enantiomers, enantioselective complexation and asymmetric catalysis.

Planar chiral halogenated ferrocenes have come in useful as synthetic intermediates over the years, allowing for the preparation of functionalized derivatives for catalysis, material science, optoelectronics, and medicinal chemistry. Despite their chemical interest, few halogenated planar chiral ferrocenes have been prepared in enantiopure form by asymmetric synthesis so far. Enantioselective HPLC on polysaccharide-based chiral stationary phases (CSPs) has been used for resolving planar chiral ferrocenes making both enantiomers available. However, the enantioseparation of derivatives containing halogens or alkyl groups exclusively remains rather challenging. Given this context, in this study the enantioseparation of eleven dihalogenated planar chiral ferrocenes was systematically explored by using five polysaccharide-based CSPs under multimodal elution conditions. Baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.15 to 1.66. Thermodynamic quantities associated with the enantioseparations were derived from van't Hoff plots, and for 1-halo-2-(iodoethynyl)ferrocenes (1-halogen = F, Cl, Br) halogen-dependent thermodynamic profiles were identified on a cellulose tris(3,5-dimethylphenylcarbamate)-based column. The impact of CSP structure and mobile phase (MP) polarity on the enantioseparation was evaluated. In addition, with the aim to unravel the functions of halogen substituents in mechanisms and noncovalent interactions underlying selector-selectand complex formation at molecular level, local electron charge density of specific molecular regions of the interacting partners were evaluated in terms of calculated electrostatic potential (V) and related source function (SF) contributions. On this basis, the impact of halogen type and position on the enantioseparation was investigated by correlating theoretical and experimental data., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The chalcogen bonding (ChB) ability of Te is studied in symmetrical diaryl ditellurides ArTeTeAr. Among the two Te σ-holes, the one along the less polarized Te-Te bond was calculated as the more electropositive. This counter-intuitive situation is due to the hyperconjugation contribution from Te lone pair to the σ* of the adjacent Te which coincides with σ-hole along the more polarized Te-Ar bond. ArTeTeAr showed notable structural features in the solid state as a result of intermolecular Te⋅⋅⋅Te ChB, such as a Te 4 rectangle through dimer aggregation or a triangular Te 3 motif, where one Te interacts with both Te atoms of a neighboring molecule through both its σ-hole and lone pair, in a slightly frustrated geometry. Lewis acidity of ArTeTeAr was also evaluated by NMR with R 3 PO as σ-hole acceptors in different solvents. Thus, 125 Te NMR allowed monitoring Te⋅⋅⋅O interaction and delivering association constants (K a ) for 1 : 1 adducts. The highest value of K a =90 M -1 was measured for the adduct between ArTeTeAr bearing CF 3 groups and Et 3 PO in cyclohexane. Notably, by using nBu 3 PO, Te⋅⋅⋅O interaction was revealed by 19 F- 1 H HOESY showing spatial proximity between CF 3 and CH 3 of nBu 3 PO., (© 2022 Wiley-VCH GmbH.)

This work reports a combined experimental and theoretical study on the new dibenzo-1,5-ditellurocine 2-Te in order to get an overview on the parameters controlling conformational change and to explain the differences with sulfur and selenium analogues. The preference of the boat conformer over the chair one is revealed by DFT calculations. For 2-Te, a ΔG value of about 3 kJ/mol was calculated, close to the value measured by NMR (5 kJ/mol). However, DFT calculations with implicit solvation effects could not clearly establish the presence of an intramolecular Te…HC noncovalent interaction (NCI), as observed in the solid state. The Independent Gradient Model (IGM) methodology discloses an existent but probably not sufficiently discriminating Te…HC NCI. It also confirms that van der Waals interactions between phenyl rings is a source of stabilization of the boat conformer. Furthermore, electrostatic potential analysis suggests that chalcogen bonds between Te σ-holes and solvent might play an important role., (© 2022 Wiley-VCH GmbH.)

Planar chiral ferrocenes are well-known compounds that have attracted interest for application in synthesis, catalysis, material science, and medicinal chemistry for several decades. In spite of the fact that asymmetric synthesis procedures for obtaining enantiomerically enriched ferrocenes are available, sometimes, the accessible enantiomeric excess of the chiral products is unsatisfactory. In such cases and for resolution of racemic planar chiral ferrocenes, enantioselective high-performance liquid chromatography (HPLC) on polysaccharide-based chiral stationary phases (CSPs) has been used in quite a few literature articles. However, although moderate/high enantioselectivities have been obtained for planar chiral ferrocenes bearing polar substituents, the enantioseparation of derivatives containing halogens, or exclusively alkyl groups, remains rather challenging. In this study, the enantioseparation of ten planar chiral 1,2- and 1,3-disubstituted ferrocenes was explored by using five polysaccharide-based CSPs under multimodal elution conditions. Baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.20 to 2.92. The presence of π-extended systems in the analyte structure was shown to impact affinity of the most retained enantiomer toward amylose-based selectors, observing retention times higher than 80 min with methanol-containing mobile phases (MPs). Electrostatic potential (V) analysis and molecular dynamics (MD) simulations were used in order to study interaction modes at the molecular level., (© 2022 Wiley Periodicals LLC.)

2'-(4-Pyridyl)- and 2'-(4-hydroxyphenyl)-TCIBPs (TCIBP = 3,3',5,5'-tetrachloro-2-iodo-4,4'-bipyridyl) are chiral compounds that showed interesting inhibition activity against transthyretin fibrillation in vitro. We became interested in their enantioseparation since we noticed that the M-stereoisomer is more effective than the P-enantiomer. Based thereon, we recently reported the enantioseparation of 2'-substituted TCIBP derivatives with amylose-based chiral columns. Following this study, herein we describe the comparative enantioseparation of both 2'-(4-pyridyl)- and 2'-(4-hydroxyphenyl)-TCIBPs on four cellulose phenylcarbamate-based chiral columns aiming to explore the effect of the polymer backbone, as well as the nature and position of substituents on the side groups on the enantioseparability of these compounds. In the frame of this project, the impact of subtle variations of analyte and polysaccharide structures, and mobile phase (MP) polarity on retention and selectivity was evaluated. The effect of temperature on retention and selectivity was also considered, and overall thermodynamic parameters associated with the analyte adsorption onto the CSP surface were derived from van 't Hoff plots. Interesting cases of enantiomer elution order (EEO) reversal were observed. In particular, the EEO was shown to be dependent on polysaccharide backbone, the elution sequence of the two analytes being P-M and M-P on cellulose and amylose tris(3,5-dimethylphenylcarbamate), respectively. In this regard, a theoretical investigation based on molecular dynamics (MD) simulations was performed by using amylose and cellulose tris(3,5-dimethylphenylcarbamate) nonamers as virtual models of the polysaccharide-based selectors. This exploration at the molecular level shed light on the origin of the enantiodiscrimination processes., (© 2021 Wiley-VCH GmbH.)

Chalcogen bonding results from non-covalent interactions occurring between electrodeficient chalcogen atoms and Lewis bases. Among the chalcogens, tellurium is the strongest Lewis acid, but Te-based compounds are scarcely used as organocatalysts. For the first time, telluronium cations demonstrated impressive catalytic properties at low loadings in three benchmark reactions: the Friedel-Crafts bromination of anisole, the bromolactonization of ω-unsaturated carboxylic acids and the aza-Diels-Alder between Danishefsky's diene and imines. The ability of telluronium cations to interact with a Lewis base through chalcogen bonding was demonstrated on the basis of multi-nuclear ( 17 O, 31 P, and 125 Te) NMR analysis and DFT calculations., (© 2021 Wiley-VCH GmbH.)

Commercial 4,4'-bipyridine is a popular scaffold that is primarily employed as a linker in 3D self-assembled architectures such as metallo-organic frameworks or as a connector in 2D networks. The introduction of alkyl substituents on the bipyridine skeleton is instrumental when 4,4'-bipyridines are used as linkers to form 2D self-assembled patterns on surfaces. Here, several synthetic strategies to access 4,4'-bipyridines functionalized at various positions are described. These easily scalable reactions have been used to introduce a range of alkyl substituents at positions 2 and 2' or 3 and 3' and at positions 2,2' and 6,6' in the case of tetra-functionalization. Scanning tunneling microscopy studies of molecular monolayers physisorbed at the graphite-solution interface revealed different supramolecular patterns whose motifs are primarily dictated by the nature and position of the alkyl chains.

The chalcogen bond (ChB) is a noncovalent interaction based on electrophilic features of regions of electron charge density depletion (σ-holes) located on bound atoms of group VI. The σ-holes of sulfur and heavy chalcogen atoms (Se, Te) (donors) can interact through their positive electrostatic potential ( V ) with nucleophilic partners such as lone pairs, π-clouds, and anions (acceptors). In the last few years, promising applications of ChBs in catalysis, crystal engineering, molecular biology, and supramolecular chemistry have been reported. Recently, we explored the high-performance liquid chromatography (HPLC) enantioseparation of fluorinated 3-arylthio-4,4'-bipyridines containing sulfur atoms as ChB donors. Following this study, herein we describe the comparative enantioseparation of three 5,5'-dibromo-2,2'-dichloro-3-selanyl-4,4'-bipyridines on polysaccharide-based chiral stationary phases (CSPs) aiming to understand function and potentialities of selenium σ-holes in the enantiodiscrimination process. The impact of the chalcogen substituent on enantioseparation was explored by using sulfur and non-chalcogen derivatives as reference substances for comparison. Our investigation also focused on the function of the perfluorinated aromatic ring as a π-hole donor recognition site. Thermodynamic quantities associated with the enantioseparation were derived from van't Hoff plots and local electron charge density of specific molecular regions of the interacting partners were inspected in terms of calculated V . On this basis, by correlating theoretical data and experimental results, the participation of ChBs and π-hole bonds in the enantiodiscrimination process was reasonably confirmed.

Positive electrostatic potential ( V ) values are often associated with σ- and π-holes, regions of lower electron density which can interact with electron-rich sites to form noncovalent interactions. Factors impacting σ- and π-holes may thus be monitored in terms of the shape and values of the resulting V . Further precious insights into such factors are obtained through a rigorous decomposition of the V values in atomic or atomic group contributions, a task here achieved by extending the Bader-Gatti source function (SF) for the electron density to V . In this article, this general methodology is applied to a series of 4,4'-bipyridine derivatives containing atoms from Groups VI (S, Se) and VII (Cl, Br), and the pentafluorophenyl group acting as a π-hole. As these molecules are characterized by a certain degree of conformational freedom due to the possibility of rotation around the two C-Ch bonds, from two to four conformational motifs could be identified for each structure through conformational search. On this basis, the impact of chemical and conformational features on σ- and π-hole regions could be systematically evaluated by computing the V values on electron density isosurfaces ( V S ) and by comparing and dissecting in atomic/atomic group contributions the V S maxima ( V S,max ) values calculated for different molecular patterns. The results of this study confirm that both chemical and conformational features may seriously impact σ- and π-hole regions and provide a clear analysis and a rationale of why and how this influence is realized. Hence, the proposed methodology might offer precious clues for designing changes in the σ- and π-hole regions, aimed at affecting their potential involvement in noncovalent interactions in a desired way.

The chromatographic performances of four coated and immobilized amylose phenylcarbamate-based chiral columns were evaluated and compared under normal phase (NP) elution conditions by using chiral 4,4'-bipyridine derivatives as analytes. n-Hexane/2-propanol 90:10 and n-hexane/2-propanol/methanol 90:5:5 mixtures were employed as mobile phases (MPs), and the effect of adding methanol in the MP on retention and selectivity was considered. The effect of temperature on retention and selectivity was also evaluated, and overall thermodynamic parameters associated with the analyte adsorption onto the CSP surface were derived from van't Hoff plots. Interesting cases of enantiomer elution order (EEO) reversal, which are dependent on the nature of polar modifier, analyte structure, column-type, and temperature, were observed. The impact of substitution pattern and electronic properties of analytes and selectors on the separation behaviour was investigated by correlating chromatographic parameters and molecular properties determined by using density functional theory (DFT) calculations. Both coated and immobilized amylose tris(3,5-dimethylphenylcarbamate) columns allowed for the baseline enantioseparation (2.0 ≤ R S ≤ 4.9) of all 4,4'-bipyridines considered in this study. These results appear particularly useful because both enantiomers of these 4,4'-bipyridine derivatives are currently under investigation as new inhibitors of transthyretin fibrillogenesis, a biochemical phenomenon which is implicated to cause amyloid diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)