New Insights into the Ion-Specific Behaviors and Design Strategies for Ion–π Interactions

Open AccessCCS ChemistryRESEARCH ARTICLE1 Mar 2021New Insights into the Ion-Specific Behaviors and Design Strategies for Ion–π Interactions Zhangyun Liu, Zheng Chen Xin Xu Liu Collaborative Innovation Center of Chemistry Energy Materials, Shanghai Key Laboratory Molecular Catalysis Innovative MOE Computational Physical Sciences, Department Chemistry, Fudan University, 200433 Google Scholar More articles by this author , *Corresponding author: E-mail Address: [email protected] https://doi.org/10.31635/ccschem.020.202000285 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesTrack Citations ShareFacebookTwitterLinked InEmail interactions play a critical role in many important biological processes, such as gene expression, nicotine addiction, ion channel function, so on, through recognizing specific ions receptors. However, widely used models, electrostatic potential quadrupole moment, either treat point charges or consider arenes only that key information carried is rarely discussed. Here, we shed light on specificities ion–π correlating binding energies new model, namely orbital energy (OEE), which describes properties both π systems detail via electron density distributions orbitals. With more detailed descriptor electrostatics, insights behind several experimental theoretical behaviors are revealed, will provide deeper understanding molecular recognition communication interactions. On top OEE an ion-specific design strategy proposed. Download figure PowerPoint Introduction Noncovalent crucial supramolecular chemistry biology.1–8 In particular, involving arene rings not prominent crystal engineering, protein folding, on,1,8–10 but also regulating processes where receptors can recognize ions, well ions.11–14 For instance, cation–π have been shown some trimethyllysine reader- proteins,15,16 discriminate degree methylation histone tails, triggering downstream processes. Meanwhile, relevance anion–π active site urate oxidase enzyme has reported.17 Hence clear physical natures cation–π8,12,14,18–26 anion–π9–10,26–38 vital tuning interactions, eventually advance development novel functional materials drugs. While great efforts devoted nature (ESP), moment (Qzz), charges, thus miss contained especially when non-spherical, linear, planar even polyhedral. Consequently, roles carrying discussed current literature. Until now, types ascribed combination effects ion-induced polarization effects.14,19–24,39–41 Thus, expected be similar. significantly different reported between them experimentally theoretically. example, according observation X-ray structures Cambridge Structural Database (CSD), cations always show strong preference ring centers, whereas it rare anions locate exactly over centers rings.42,43 Besides, optimizations often lead single type minimum structure complexes, while there feasible modes contact lie above rings.42 The “aromatic box” consisting aromatic components exists processes11–14 applied artificial hosts.14,35–38 additivity influence selective ion. nonadditivity still elusive. Jiang et al.44 bindings sandwich complexes additive using Me4N+ typical cation, (BEs) approximately twice BEs respective half-sandwich complexes. other results showed π–cation–π generally nonadditive.45,46 hand, majority approximate geometries BEs.47–50 Nevertheless, how understand investigation individual complex, apply total BE decomposition51–54 perform subsequent analysis various origins.31,33–34,55–57 context finding trend set direct convenient correlate with certain descriptors, example ESP Qzz, commonly done literature.19,21,24–25,39,58,59 these descriptors capture fundamental physics under study. present work, report comparative order reveal determines their behaviors. We (OEE),60 Our differentiate showing make contributions former dominant contributor here quantitative differences brought qualitative natures. explored interactions: (1) strength (i.e., Li+ > Na+ K+) alkali bonded benzene (BEN), selectivity channels, mainly determined instead believed. (2) small rely effects. unexpectedly (3) significant (4) It drive prefer center, because planes rings. Based from Details XYG3 doubly hybrid DFT XYG361 (xDH) theory (DFT) remarkably accurate describing noncovalent main group elements.62–71 Here fully optimize all 6-31+G(d) basis related systems, 6-31G(d) derivatives naphthalene, anthracene, triphenylene. calculations then performed optimized at XYG3/6-311++G(3df,2p) level counterpoise corrections superposition error (BSSE).72 values OEEs ESPs B3LYP/6-311++G(3df,2p) method. This way accord fact method uses B3LYP orbitals densities input its final evaluations. To estimate contribution replace spherical complex dummy probe atom evaluate value point. All out local version Gaussian 09 package.73 model interpret underlying physics, decomposed effect, exchange correlation Pauli repulsion, charge transfer contribution, on.51–53,57 Among terms, effect two unperturbed A B easily quantified, coined OEE,60,67 follows: = − ∑ Z ∫ ρ Ion ( r → ′ ) | R d + (1)where refers system ZA, ZB RA, RB eq 1 positions nuclei B, respectively, M i occ φ 2 (M Arene π, Ion) isolated monomer obtained occupied { } . first terms describe nuclei–electron attractions vice versa. last repulsions electron–electron nuclei–nuclei, respectively. Hence, considers details monomers systems. As excellent linear correlations, corresponding intercepts, zero, interpreted “non-electrostatic” termed NEE, together.60 Results Discussion Different Numerous studies demonstrated interactions.14,19–24,29–34,39–40,58,67 Due simplicity, (e.g., Na+) halogen Cl–) employed exploring Usually, treated (with opposite signs) models based Qzz rings.14,19,21,24,25,29,31–34,39,58–59 improve utilize takes account those interacting (see “Computational Details” section). particularly useful description unsymmetrically shaped difficult apply. validity electrostatics examined comparing model. Na+–benzene (BEN, −8.45 B)30 Cl−–hexafluorobenzene (HFB, 9.50 examples.40,42,74 Figure plots profiles Na+–BEN Cl−–HFB lying C6 symmetry axis. Both computed function distance centroid. When far away rings, almost identical, means long distances. equilibrium distances (around 2.4 Å 3.2 Cl−–HFB), (−14.14 kcal mol−1) slightly negative than −ESP (−13.30 (−18.07 (−8.36 complex. These illustrate that, reasonable cation interaction substantially underestimated latter demonstrates anion being Therefore, quantify (red lines) (blue (a) (b) Cl−–HFB, ion-centroid (Re, Å). arrows indicate scans without geometry relaxations Dougherty co-workers adopted rationalize variation abilities series factors absorbed constant term (NEEs).19,21,24 now used. metal general argue important, quantitatively, qualitatively, employ model60 place, remaining NEEs described accurately. construct OEEs, 35 20 Supporting Information S1 ranging substituted benzenes, heterocycles, cyanuric acid similar core. choose six comparison: Li+, Na+, K+, F−, Cl−, Br− (Figure 2). multiply [(NH2)3C+, NH4+, N3−, NO3−, BF4−] provided S2. 2, faithfully conveniently mirror trends invoking intensive decomposition analyses. NEE values, indicated −26.10, −13.37, −8.98 mol−1 Li+–π, Na+–π K+–π larger size produces weaker contribution. addition, NH4+–π −8.61 (as S2), close size.14 expected, component mostly polarization.21 reluctant donate accept electrons, suggests including covalent interaction, negligible. compact dispersion near each ion, makes net attractive Binding (BEs, plotted versus (OEE, Li+–π (c) (d) F−–π (e) Cl−–π (f) Br−–π Slope*OEE defines “nonelectrostatic” 0. correlations OEEs. slopes relations 1.0, obviously less 1.0 (≍ 0.6–0.7). comparison indicates repulsive linearly scaled effect. fact, repulsion caused diffuse anions. −3.34, −1.66, −0.15 F−–π, Cl−–π, smaller Moreover, S2, comparatively (−2.89, −1.47, −1.43 N3−–π, NO3−–π, BF4−–π respectively), compared Note vanish become unfavorable ≥ 0), exist appreciable no case left once again provides indication Physically, ability polarize tendency polarized. Roughly, shorter intermolecular ions-π density. stronger electric field produced does large arenes, electron-rich polarizable electron-deficient ring. simple proposed Information, S3, Table S4 S5) distribution polarizability intensity inversely proportional square distance. supports our findings Understanding Li+–BEN K+–BEN Revealing channels. BEN gets larger, gradually weakened. believed result effect.12,14,20–21 Through separating BEs, conclusion revisited here. true 3a, Li+–BEN, Na+–BEN, same BEs. should noted reference 0.44 2.88 mol−1, weaker, although 14.10 20.87 weaker. K+–BEN, effects, 12.73 17.12 Li+–BEN. addition actually plays sequences metals benzene. 3 mol−1), (NEE, (BE, centroids Å) Li+–Benzene Na+–1,3,5-trifluorobenzene (TFB), Cl−-1,3,5-TFB, Na+–triazine (TAZ), Cl−–TAZ driving force negligible 1,3,5-trifluorobenzene (TFB, 0.57 B) triazine (TAZ, 0.90 B), thought contribute complexes.33,40 favorable considered solid evidence existence importance interactions.33,40 3b, Na+–TFB (−1.74 clearly (−13.37 consistent previous suggestions.33,40 Cl−–TFB despite positive (−6.75 (−5.99 (−1.66 minor. suggested work,51 conclude here, OEE, contributes most offset leading term. 3b. demonstrate dependent analyses, powerful tool Nonetheless, usually underestimate overestimate treating charge, further highlights energy. drugs hosts; however, elusive.44–50 New required physics. π–ion–π employed, characterized BEadd, defined difference 4, C+–BEN (C+ NH4+) obvious nonadditivity, Me4N+–BEN shows good additivity. (Cl−, Br−, BF4−)–HFB additive, F−–HFB additive. work.44–50 π–π sandwiches (BEπ–π) ignorable seen S1), they do impact separation. OEEadd 4). dipoles effect) generated subsystems other, nonadditivity. Furthermore, distance, forces. controlled nonadditive nonadditive. fine additivity, longer weakens poor strengths size, (e.g. Me4N+) BF4−) highly relies information, sensitive depends size. 4 Calculated (kcal Benzene (BEN) hexafluorobenzene (HFB) chosen hosts bind anions, BES complexation BEs(π–ion–π) E(π–ion–π) – E(ion) 2E(π). BEHS fragments’ pairs. BEHS(ion–π) E(ion–π) E(π). BEadd BEadd(π–ion–π) BEs(π–ion–π)–2BEHS(ion–π). OEEadd(π–ion–π) OEES (π–ion–π)–2OEEHS(ion–π). preferred locations 5 carbon periphery. Good observed Detailed calculation data summarized Tables S2 S3. Cl− binds emphasized, Taking hexamethylbenzene (HMB) −19.92 −13.37 making −34.10 sitting center. represents strongly bounded studied work. weakest occurs −1.57 compensates (9.61 achieve binding. becomes periphery, significance moved location center decreases 2.15 2b) −11.22 5a). resistant against movement th