Extended enantiopure ortho-phenylene ethylene (o-OPE)-based helical systems as scaffolds for supramolecular architectures: a study of chiroptical response and its connection to the CISS effect

ORGANIC CHEMISTRY FRONTIERS RESEARCH ARTICLE Cite this: Org. Chem. Front., 2021, 8, 5071 Received 29th May 2021, Accepted 28th June 2021 DOI: 10.1039/d1qo00822f rsc.li/frontiers-organic Extended enantiopure ortho-phenylene ethylene (o-OPE)-based helical systems as scaffolds for supramolecular architectures: a study of chiroptical response and its connection to the CISS effect† Ana M. Ortuño, a Pablo Reiné, a Sandra Resa, a Luis Álvarez de Cienfuegos, a Victor Blanco, a José Manuel Paredes, b Antonio J. Mota, * c Giuseppe Mazzeo, d,e Sergio Abbate, d,e Jesus M. Ugalde, f Vladimiro Mujica,* f,g Giovanna Longhi, * d,e Delia Miguel * b and Juan Manuel Cuerva * a A novel synthetic strategy based on a bifunctional stapled chiral nucleus from which segments of different lengths can be added to both ends of o-phenylene ethynylenes (o-OPEs) has been developed to obtain a new type of foldamer and a novel chiral Pd 2 L 2 metallacycle. For the first time, an enantiopure fully conjugated helical foldamer having 14 phenyl rings and 13 alkynes is reported. The folded structure has four complete loops and is able to host three Ag(I) cations in their cavity with high binding constants. The complete photophysical and chiroptical (ECD, CPL and VCD) characterization of these foldamers has shown that these molecules show intense chiroptical responses with dissymmetry ratios in the range of 10 −2 . Theoretical modeling of these systems reveals the origin of these remarkable responses and points out a potential connection with the chiral induced spin selectivity (CISS) effect. The magnetic dipole moment is proposed as a key physical variable connecting the chiroptical properties and CISS-based spin filtering properties observed in chiral compounds. Introduction Helical structures are widespread motifs in biomolecules and many efforts have been made to imitate such geometries using abiotic components. 1 Thus for example, [n]-helicenes have attracted the attention of chemists for almost a century. 2,3 Particularly appealing is the fact that they present a conjugated system arranged in a helical geometry, which is preserved beyond [6]-helicenes. Their chiroptical properties, derived from their intrinsic chirality, such as optical rotatory dispersion (ORD), electronic circular dichroism (ECD), vibrational circular dichroism (VCD), Raman optical activity (ROA) and more recently, circularly polarized luminescence (CPL), 4,5 are in fact remarkable, and have been extensively studied. Moreover, the helical geometry is also relevant in other fields. It has been suggested that conductive helical arrangements are of importance in the context of the chiral induced spin selectivity (CISS) effect 6 once they can be prepared as enantiopure entities. The CISS effect is based on the phenomenon of electron spin polarization in electron transfer, electron transport and bond polarization processes in chiral molecules. Although initial experiments were based on biomacromolecules, 7 it is †Electronic supplementary information (ESI) available: Additional figures and tables referred to in the main text, the experimental details for NMR, IR, ECD, CPL and VCD measurements, the details of the conformational analysis, the computational aspects of the spectral calculations and data treatment. CCDC 2073558. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d1qo00822f a Department of Organic Chemistry, Faculty of Science, Universidad de Granada (UGR), Unidad de Excelencia de Química (UEQ), E-18071 Granada, Spain. E-mail: [email protected] b Department of Physical Chemistry, Faculty of Pharmacy, UGR-UEQ. E-mail: [email protected] c Department of Inorganic Chemistry, Faculty of Science, UGR-UEQ. E-mail: [email protected] d Department of Molecular and Translational Medicine, Università di Brescia, Brescia, Italy e Istituto Nazionale di Ottica –CNR, Brescia Research Unit, via Branze 45, 25123 Brescia, Italy. E-mail: [email protected] f Kimika Fakultatea, Euskal Herriko Unibertsitatea and Donostia International Physics Center (DIPC), P. K. 1072, 20080 Donostia, Euskadi, Spain g Arizona State University, School of Molecular Sciences, Tempe, AZ 85287, USA. E-mail: [email protected] This journal is © the Partner Organisations 2021 Org. Chem. Front.,2021,8,5071–5086 | 5071 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online View Journal | View Issue worth noting that it has also been observed in in fully conjugated [7]-helicene and in other helicene-like molecules. 8 Consequently, fully conjugated helical molecules have been theoretically suggested as interesting candidates for spintronics, quantum sensing and quantum information applications. 9–11 Moreover, the remarkable geometry of [6]-helicenes has also been used in the context of chiral metallosupramolecular architectures 12,13 as bidentate donors with an angle between the binding sites close to 0°. 14 These systems have emerged as an unique research field owing to their electronic, optical and sensing capabilities. However, the main drawback in [n]-helicene chemistry is the challenging synthesis of members with increasing turns, even in their racemic form. In fact, the longest member of the series, [16]-helicene, composed of two and a half turns, represents an isolated example (Fig. 1, top). 15 Although longer related helicene-like molecules (two and a half turns) have been described, easy access to fully conjugated helical systems continues to be a synthetic challenge. 16,17 Therefore, easy-to-prepare extended and conjugated helical systems would be highly desirable for important applications like those mentioned above. Within this context, foldamers based on conjugated subunits constitute a privileged scaffold for a number of different reasons: (i) they can be easily prepared by iterative protocols using simple conjugated monomers with different geometries, (ii) the functionality present in such monomers can cooperatively act to strengthen their properties or even create new ones, and (iii) they can also interact dynamically with the environment. In fact, many aromatic foldamers can be switched between different states by different stimuli such as the presence of light, 18–22 changes in temperature, 23–26 solvent composition, 27 anions, 28–32 cations, 33,34 or water 35–38 binding, and redox processes. 39,40 Moreover, foldamers are able to generate chirality in a dynamic way even using achiral monomers/repeating units. Therefore, the control of the P/M helicity 41–46 yields systems that are able to act as chiroptical probes 47,48 or even CPL emitters. 49–53 In recent years, we have been working on conjugated helical structures based on o-OPEs 54–58 as an alternative to [n]-helicenes exhibiting, in many cases, better chiroptical responses. Our approach relies on widening the inner cavity present in [n]-helicenes, which translates into an enhancement in the magnetic moment of optical transitions and the corresponding chiroptical response, especially at the longest wavelength. Thus, we have developed two strategies to obtain enantiopure folded fully conjugated helical systems: the first based on the use of chiral sulfoxides 59,60 and, secondly, the use of chiral staples, demonstrating that enantiopure P/Mhelixes can be also prepared by efficient chirality transfer from a chiral staple to the o-OPE core, including even double staples to avoid racemization processes. 61–64 However, the later systems could be synthesized with only one turn and a half. 65 All the above approaches provide structures with remarkable chiroptical responses in ECD, CPL and VCD. It is worth noting that the response of ECD in terms of molar circular dichroism has been for some time correlated with the magnitude of the chiral-induced spin selectivity (CISS) effect. 66 Actually, this phenomenon has been recently discovered, offering a promising change of paradigm for the discrimination and filtering of spin states. The spin of the electron, S= 1 2, yields two quantum states characterized by its projection on Fig. 1 Top: Previous studies with foldamers and helicene-type systems with more than two loops. Bottom: New helical systems developed in this work: chemical structure of stapled nucleus (S,S,P)-1, helical systems (S,S,P)-2-(S,S,P)-6, ligand (S,S,P)-7and metallosupramolecular complex ((S,S,P)-7) 2 Pd 2 . Research Article Organic Chemistry Frontiers 5072 |Org. Chem. Front.,2021,8,5071–5086 This journal is © the Partner Organisations 2021 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online a given axis, m s =± 1 2. The two states are degenerate in the absence of either internal or external magnetic fields and, consequently, any electron current under such circumstances will consist of a half–half mixture of both states. The separation of the spin states of the electrons is a milestone of the greatest importance for the development of spintronics. Although spin states of neutral particles 67 can be selected passing through an in-homogeneous magnetic field, charged particles, like electrons, suffer from the Lorentz force arising from the interaction of the electric charge with the magnetic field, preventing a Zeeman’seffect-based technique to be used for separating electron spin states. Although more complex architectures can be used, 68 the (preferential) selection of the spin state of electrons travelling through chiral structures is highly appealing. The chemically relevant fact is that now it is the scattering of electrons through the molecular (helical) structure that induces the filtering of the electron spin states. Namely, depending on the helicity of the molecular structure, it preferentially allows the passage of one of the two spin states over the other, because helicity couples the spin of the electron with its own linear momentum, resulting in the selective transmission of electrons with the preferred spin state. This opens the way to great opportunities for “chemical control”in the selection and discrimination of the spin state of electric currents. The key concept resides in the achievement of precise chemical control on the factors affecting the molecular helical structure, i.e. length, diameter, pitch, chemical composition, chemical environment, either the solvent selection or its deposition on selected surfaces, including nanoparticles, etc. The absence of external electromagnetic fields avoids any interference with the spins in “uncontrollable”ways. The implications of the CISS effect for the control of the electronic spin state have already been documented. 69 Nevertheless, a long-standing goal, not fully resolved at the time being, is to know beforehand which molecules are best for CISS spin-filtering. Within this context, remarkable effort has been made by Waldeck et al., 66 who showed conclusive experimental evidence for the direct correlation between CISS induced spin-filtering power and the magnitude of features of the molecule electronic circular dichroism (ECD) spectrum. A direct correlation of the dissymmetry of the electron-transfer rate for photoelectrons produced by circularly polarized light was found with both the sign and intensity of the ECD signal of electron acceptor chiral molecules. This suggests that the larger the ECD signal intensity the better the CISS spin-filtering a molecule can perform. The sign determines which spin is preferentially filtered. Although the relationship between both phenomena seems plausible, it is not clear which factors are relevant for such a connection. One conceivable hypothesis is that the CISS effect may be associated with a transient magnetic moment in chiral molecules. Indeed, the intrinsic magnetic nature of the CISS effect suggests that induced magnetic transition moments (m) could be relevant to characterize the magnetic molecular response associated with the dynamic spin-polarized electron transport through a molecule. The optimal design of structures in which such a relationship could be validated is, therefore, essential. Here we report on a versatile scaffold to explore new helical architectures using simple derivatizations. Chiral stapled nucleus (S,S,P)-1can be used as a chiral seed for the synthesis of highly extended enantiopure conjugated helical systems (S, S,P)-2–(S,S,P)-6(Fig. 1, bottom) containing one up to four complete turns. In the presence of Ag(I) we have obtained the most extended enantiopure systems with a well-defined structure described to date. 70–73 This situation is optimal to gain insight into the importance of the length of helical systems, the magnitude of the magnetic dipole transition moment (m) associated with the less energetic transition, and their potential use as a predictor of CISS capabilities for an organic architecture. We must emphasize that a comprehensive theoretical model coupling optical dichroism with the CISS effect is still missing, but the work reported here may be a step forward in this direction. Moreover, the usefulness of (S,S,P)-1is also demonstrated with the preparation of ligand (S,S,P)-7. This compound increases the toolbox of the supramolecular research area showing that simple helical foldamers can be also used as a building block for the Pd(II)-directed self-assembly of a chiral Pd 2 L 2 metallacycle, thus expanding the scarce number of examples of chiral metallosupramolecular architectures reported to date. 13 Results and discussion Synthesis The main objective of our approach is the synthesis of a chiral core able to be further functionalized. Taking into account our previous successful route to enantiopure stapled o-OPEs based on an etherification reaction of a simple o-OPE and a chiral bis-tosylate derivative, 53 we decided to adopt this strategy to access compound (S,S,P)-1. Hence, this compound could be easily prepared following the route described in Scheme 1. (S, S,P)-1presents two aromatic bromides suitable for symmetric Scheme 1 Synthesis of helical systems (S,S,P)-2–(S,S,P)-6and ligand (S, S,P)-7. Reagents and conditions: (a) Ac 2 O (1.4 eq.), DMAP (2 eq.), CH 2 Cl 2 , rt, 5 min, 100%; (b) Pd(CH 3 CN) 2 Cl 2 (0.03 eq.), PtBu 3 ·HBF 4 (0.06 eq.), CuI (0.03 eq.), iPr 2 NH, rt, 24 h, 70%; (c) K 2 CO 3 (7 eq.), THF, MeOH, rt, 30 min, 88%; (d) CsCO 3 ,CH 3 CN, reflux, 24 h, 56%; (e) Pd(CH 3 CN) 2 Cl 2 , CuI, PtBu 3 ·HBF 4 , iPr 2 NH/THF, 60 °C, 24 h; (f) Pd(CH 3 CN) 2 Cl 2 , CuI, PtBu 3 ·HBF 4 , iPr 2 NH/THF, 60 °C, 24 h; 81%. Yields of step e for each derivative are described in the ESI.† Organic Chemistry Frontiers Research Article This journal is © the Partner Organisations 2021 Org. Chem. Front.,2021,8,5071–5086 | 5073 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online extension of the conjugated system using different Sonogashira reactions. Enantiomeric (R,R,M)-1was also prepared resulting in the expected and opposite chiroptical properties (see Fig. S118 and S134†). For simplicity, from now on the discussion is restricted to (S,S,P)-1enantiomer. A simple coupling reaction affords enantiopure compounds (S,S,P)-2to (S,S,P)-6with increasing number of alkynes, enabling the study of systems from three alkynes/one turn, (S,S,P)-1, to thirteen alkynes, (S,S,P)-6, reaching in the latter case four complete turns, which has no precedent in the literature. The coupling reaction of the chiral nucleus (S,S,P)-1with pyridinecontaining dialkyne 19 yielded (S,S,P)-7. These reactions demonstrate that (S,S,P)-1is in fact a versatile chiral building block that enables access to a variety of structures in a straightforward and modular way. Photophysics of compounds (S,S,P)-1 to (S,S,P)-7 Compound (S,S,P)-1was fully characterized by NMR and mass spectrometry (see the ESI†) but also by means of optical and chiroptical techniques. The absorption spectrum in CH 2 Cl 2 exhibits two main bands centered at 305 nm and 290 nm with a smooth shoulder around 350 nm (Fig. 2a). On the other hand, the emission spectrum presents one band at 410 nm (Fig. S110†) with a fluorescence quantum yield of 4.6% (Table S1†). Circular dichroism of (S,S,P)-1(CH 2 Cl 2 ) showed a positive Cotton effect at the longest wavelength, Δε= +47 M −1 cm −1 , which is characteristic of Phelicity (Fig. 2b). We note that molar circular dichroism (Δε) depends on the intensity of absorption (that is, on electric transition dipole moment) and its magnitude cannot be always correlated with the intrinsic chirality of the sample. In that situation, a dimensionless g abs value, Δε/ε, is more representative and easy to compare with theoretical values. Nevertheless, extracting reliable experimental g abs values from ECD bands is tricky since calculations predict energetically close transitions with the opposite sign, such that the observed g abs value results from the algebraic sum of g-values for the individual transitions. Being interested in the first electronic transition, the best estimate can be obtained from the tail of the CD band. In that case, the experimental g abs value (+1 × 10 −2 ) is comparable to previously described values for related systems. 52,53 The origin of this helical chirality could be clarified using density functional theory (DFT) calculations. After a molecular mechanics (MM) conformational search, all structures within 5 kcal mol −1 have been optimized with both Pand Mhelicities at the B3LYP/6-31G** level in CH 2 Cl 2 , treated with the polarizable continuum model (PCM). Only three conformers, corresponding to the relative spatial orientations of the bromine atoms (out–out,out–in and in–in), have been obtained with non-negligible populations (Fig. 2c and Table S10†). They all present Phelicity and, considering the calculated energy, are nearly equally populated. As a consequence, the Pepimer dominates the conformational equilibrium and makes possible a definite assignment of the (S,S,P)-1absolute configuration in solution. This conclusion was strengthened by the similarity between the averaged simulated ECD and absorption spectra of the abovementioned Pconformers (M06/6-31G** level) and the experimental ones (Fig. 2a and b). The calculated g abs value for the longest wavelength transition is in reasonable agreement with the experimental one. Fortunately we could also obtain the single-crystal X-ray diffraction structure of (S,S,P)-1, which confirms its helical Fig. 2 Comparison of the calculated (dashed orange, purple and green) and experimental (black) (a) absorption and (b) ECD spectra of (S,S,P)-1 in CH 2 Cl 2 (2.5 × 10 −5 M); (c) X-ray structure of (S,S,P)-1and calculated structures of the in/in,in/out and out/out conformers. Calculated spectra are 20 nm blue-shifted and their intensity divided by a factor of two. Research Article Organic Chemistry Frontiers 5074 |Org. Chem. Front.,2021,8,5071–5086 This journal is © the Partner Organisations 2021 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online geometry with Ppreference in the solid state (Fig. 2c). This helical arrangement generates a dihedral angle between the central aromatic rings close to 40°. The outer aromatic rings adopt a parallel orientation, although displaced, with a distance between their main planes of 3.5 Å and a distance between centroids of 3.8 Å, suggesting the establishment of π-stacking interactions between them. Being dynamic systems, foldamers are affected by the environment and, consequently, their properties are usually solvent dependent. In this case, we only observed a single set of signals in NMR, showing that any conformational equilibrium takes place faster than the NMR timescale. The absorbance and fluorescence of (S,S,P)-1were analyzed in different solvents, including apolar, polar and protic ones. Although no significant differences were observed in the emission spectra, a slightly increment of the shoulder in the absorbance spectra was observed in some solvents (Fig. S109†). Fluorescence lifetimes were also measured at the emission maximum using an excitation source of 325 nm. In all tested solvents, decays were fit to a biexponential function where the shortest fluorescence lifetimes were around 0.5 ns in most cases, except in CH 2 Cl 2 in which it presented a considerably lower value of 0.2 ns. However, we observed higher differences for the longest fluorescence lifetimes, which varied between 0.7 ns in CH 2 Cl 2 to 4.1 ns in toluene (see Table S2†for more details). In view of these results we recorded the time-resolved emission spectra (TRES) of compound (S,S,P)-1in CH 2 Cl 2 covering all of the emission range, between 340 and 600 nm. This global analysis also afforded a biexponential decay showing, along the whole spectra, an exclusive contribution of the shortest lifetime species, the presence of the largest being almost negligible (see Fig. S106†). Regarding chiroptical properties and according to the abovementioned data, minor changes in the ECD of (S,S,P)-1were observed. We noticed that the chiroptical response of (S,S,P)-1is maximized in MeOH with an experimental g abs value of +1.3 × 10 −2 . Since (S,S,P)-1is fluorescent and chiral, CPL is a valuable tool to extract information of the dynamic system. Although the fluorescence was weak, reliable dissymmetry factors of the emission, g lum values defined as 2(I L −I R )/(I L +I R ), could be measured (CH 2 Cl 2 :g lum = +1.1 × 10 −2 , MeOH: g lum = +1.0 × 10 −2 , MeCN: g lum = +1.0 × 10 −2 ,n-hexane: g lum = +0.9 × 10 −2 ). These results suggest that the Phelicity is preserved in the excited state. Consequently, the similarity of g abs and g lum values also reveals that the structure is highly preserved in the excited state despite the apparent conformational flexibility. Analogous studies were carried out with compounds (S,S)-2 to (S,S)-7(Fig. 3). Again, chiroptical properties, especially ECD and CPL, were highly informative and solvent dependent. The compound presenting five alkynes, (S,S,P)-2, showed remarkable molar circular dichroism in MeCN (Δε= +41 M −1 cm −1 , g abs = +1.0 × 10 −2 ), being compatible with a relatively ordered structure. Again, we found a correlation between the polarity of the solvent and the g abs value for the longest wavelength transition, with similar values in MeOH (Δε= +36 M −1 cm −1 , g abs = +1.4 × 10 −2 ) to those obtained in MeCN, but being weaker in CH 2 Cl 2 (Δε= +20 M −1 cm −1 ,g abs = +0.8 × 10 −2 ) and hexane (Δε= +20 M −1 cm −1 ,g abs =+1×10 −2 ). If we assume g abs values as the representative parameter of the system helicity, Fig. 3 Experimental (solid line) and calculated (dashed line) ECD spectra of (a) (S,S,P)-2and (S,S,P)-3and (b) (S,S,P)-4–(S,S,P)-7in MeCN (calculated spectra are 20 nm shifted) and (c) CPL spectra of (S,S,P)-2-(S, S,P)-7in MeOH. Organic Chemistry Frontiers Research Article This journal is © the Partner Organisations 2021 Org. Chem. Front.,2021,8,5071–5086 | 5075 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online polar solvents are apparently favoring the folding process. Although this is a well-known effect for m-OPEs, 27 this is the first time it is clearly observed for o-OPEs. Theoretical calculations support the prevalence of the fully folded conformations both considering CH 2 Cl 2 and acetonitrile in the polarizable continuum model using the integral equation formalism variant (iefpcm) (see the ESI†), showing again a clear preference for the Pconformation. 74 The rotational barrier for the unfolding process was theoretically estimated by turning one arm of the folded structure in 10 0 steps (Fig. S156†), achieving a maximum at 8.1 kcal mol −1 . Therefore, the partially disordered situation favored by less polar solvents might explain the observed differences (see Fig. S119, in the ESI†). Compound (S,S,P)-2is also fluorescent, with quantum yield values varying from 19% to 29% depending on the solvent (see Table S3 in the ESI†). The fluorescence lifetime at the emission maximum showed again two values around 4 and 2 ns in all solvents. Interestingly, time-resolved fluorescence allows the deconvolution of the emission spectra, providing the ratio of the different emitting species by using the areas of the speciesassociated emission spectra (SAEMS). In the four solvents we could detect two main contributions coming from two different species with around 4.6 and 2.6 ns, which cannot interconvert in that timescale. Although relative proportion depends on the solvent nature (see Fig. S107†), two limit situations are present in hexane and MeOH, in which the corresponding populations are reversed. The coexistence of fully folded and partially folded structures in the excited state may be a reasonable explanation, fully folded structures being maximized in MeOH. Since the chiroptical properties of the abovementioned species are expected to be different, CPL is once again a valuable tool to extract information on the dynamic system. Representative solvents as MeOH, MeCN, CH 2 Cl 2 and hexane were evaluated using this technique, obtaining remarkably high g lum values (MeOH: +1.3 × 10 −2 , MeCN: +1.3 × 10 −2 , CH 2 Cl 2 : +0.88 × 10 −2 , hexane: +1 × 10 −2 ). Once more, a correlation with the polarity of the solvent was observed, the fully folded conformations with higher g lum values being preferred in MeOH or MeCN. The positive sign of CPL is correlated with the positive sign of the ECD signal for the longest wavelength transition, Phelicity being preserved in the excited state. 4 The similarity of g abs and g lum values also reveals that the geometrical structure of the ground state is preserved in the excited state. In fact, the optimized structure for the first excited state starting from the lowest-energy fully folded ground state structure resulted in a nearly superimposable helix in both ground and excited states, showing differences only in the bond length alteration (BLA) of the C–CuC–C groups (see Fig. 4f and Table S12†). Similar conclusions were extracted for (S,S,P)-3–(S,S,P)-5 and (S,S,P)-7. Molar circular dichroism and g abs values remain high, especially in MeCN ((S,S,P)-3:Δε= +21 M −1 cm −1 ,g abs = +0.9 × 10 −2 ;(S,S,P)-4:Δε= +18 M −1 cm −1 ,g abs = +0.5 × 10 −2 ;(S, S,P)-5:Δε= +47 M −1 cm −1 ,g abs = +0.9 × 10 −2 ;(S,S,P)-7:Δε= +19 M −1 cm −1 ,g abs = +0.8 × 10 −2 ), compared to CH 2 Cl 2 ((S,S,P)- 3:Δε=+6M −1 cm −1 ,g abs = +0.3 × 10 −2 ;(S,S,P)-4:Δε=+8M −1 cm −1 ,g abs = +0.3 × 10 −2 ;(S,S,P)-5:Δε= +13 M −1 cm −1 ,g abs = +0.3 × 10 −2 ;(S,S,P)-7:Δε= +19 M −1 cm −1 ,g abs = +0.3 × 10 −2 ), although exceptions can be also observed (see the ESI†). These higher g abs in MeCN suggest a relatively ordered structure in more polar solvents, in accordance with the stability of the helical structure. Nevertheless, the increasing number of potential conformations did not allow a complete modeling of the conformational space as in previous cases. Even so, it seems reasonable to assume that in the absence of solvophobic interactions many more disordered structures in solution could be present. For compound (S,S,P)-6, we found some solubility issues in hexane and MeOH and reliable CD spectra could be obtained only in CH 2 Cl 2 (Δε= +13 M −1 cm −1 ,g abs = +0.3 × 10 −2 ) and MeCN (Δε= +15 M −1 cm −1 ,g abs = +0.3 × 10 −2 ). Fluorescence lifetimes and quantum yields for such longer oligomers (S,S,P)-3-(S,S,P)-7were evaluated in MeOH, MeCN, CH 2 Cl 2 and hexane and are summarized in Table S4.† Quantum yields depend on both the solvent and number of alkynes present in the molecule, but no sensible relationships Fig. 4 Optimized DFT (B3LYP/6-31G**) structures of: (a) (S,S,P)-2; (b) (S,S,P)-3; (c) (S,S,P)-4; (d) (S,S,P)-5; (e) (S,S,P)-6. Color coding: C, gray; O, red. H atoms have been omitted for clarity; (f) ground-excited structures and transitions for (S,S,P)-2in absorption (left) and emission (right). Research Article Organic Chemistry Frontiers 5076 |Org. Chem. Front.,2021,8,5071–5086 This journal is © the Partner Organisations 2021 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online could be obtained in any of the cases. However, it is remarkable that, except for compound (S,S,P)-3, the intensity-averaged lifetime of longer oligomers is always lower in hexane (around 3 ns) than in MeOH and CH 3 CN (around 4 ns), showing again a higher contribution of the shortest lifetime species in apolar solvents, in accordance with the results obtained for TRES of the first member of the series (S,S,P)-2. All helical systems were also very efficient CPL emitters, especially in MeOH ((S,S,P)-3,g lum = +1.3 × 10 −2 ,(S,S,P)-4,g lum = +1.1 × 10 −2 ,(S,S,P)-5,g lum = +1.3 × 10 −2 ,(S,S,P)-6,g lum = +1.3 ×10 −2 ,(S,S,P)-7,g lum = +0.54 × 10 −2 ). Modeling CPL properties has been be carried out for compound (S,S,P)-2in the most stable folded conformer. However, the analysis of larger systems is computationally too demanding. Despite this limitation, the structures were optimized by DFT calculations (Fig. 4b–e). Although, the similarity between g abs and g lum values, which is also observed in experimental trends, is expected, the g lum value is controlled by the S 1 →S 0 transition, which cannot be assumed to be identical to the S 0 →S 1 transition because the structural changes in the excited state may affect the ground state transition parameters. (S,S,P)-1–(S,S,P)-7 Ag(I) complexes Stapled o-OPEs present a perfect arrangement for the coordination of Ag(I) cations (AgBF 4 ) using carbophilic interactions. In this case, we restricted our study to CH 2 Cl 2 owing to the incompatibility of such interactions and polar coordinating solvents. The first member of the series, (S,S,P)-1, presents evident structural changes after Ag(I) addition as we observed an increased resolution and downfield shielding of the aromatic protons (Fig. S49†). Regarding the 13 C NMR spectra, alkyne carbons, which were initially located within 1 ppm to around 92 ppm, evolve to three different signals at 89, 92 and 94 ppm by coordination with the Ag(I) cation (Fig. S50†). The coordination process was also followed by ECD spectroscopy (Fig. S126†). In this particular case, we observed a decrease in the chiroptical response. This fact is in agreement with previous results in related o-OPEs with three alkynes owing to a planarization of the helical structure. ECD titration experiments resulted in a relatively strong single binding event, K 1:Ag =32480±2%M −1 . Theoretical calculations (M06/6-31G* plus LANL2DZ (valence + ECP) for silver in CH 2 Cl 2 ) showed that the minimum energy structure corresponds to a distorted trigonal bipyramidal geometry (Fig. 6b) in which the bromine atoms participate in the coordination to the Ag(I) cation. Compound (S,S,P)-2is expected to behave as a ligand for only one Ag(I) cation taking into account the previous studies of related o-OPE systems. 61 The binding process can be again properly followed by 1 H NMR spectroscopy. NMR titrations showed that the original signals of ortho hydrogen atoms of the inner phenyl rings experience the characteristic deshielding (i.e. from 6.45 ppm to 6.64 ppm, Fig. 6a) attributed to Ag(I) coordination. In addition, significant changes in the chemical shift of alkyne carbons were observed in the 13 C NMR spectrum (Fig. S52†). The ECD response at the longest wavelength is intense (Δε= +85 M −1 cm −1 ,g abs = +2.5 × 10 −2 ) in agreement with a well-defined helical structure upon the formation of the complex (Fig. 6). It is worth noting that such a dissymmetry ratio is huge compared with usual values for organic molecules at the longest wavelength. The corresponding ECD titration showed a high binding constant K 2:Ag = 3.67 × 10 5 ±5% M −1 . As expected, the DFT-based conformational analysis (see the ESI†) of complex (S,S,P)-2:Ag is in agreement with experimental findings, showing a stabilization of the fully folded structure. The calculated ECD is also in good agreement with the experimental one, thus confirming the folding process with Ag(I) (Fig. 5a and 6c). In this case, the distorted trigonal bipyramidal geometry is generated by coordination with five alkynes. Ag–alkyne bond distances are predicted to lay within 2.51–2.69 Å, with the Ag–C (alkyne) distances ranging from 2.57 to 2.76 Å. The distance between the terminal aromatic rings of the side arms and those on the corners on the central core of the helix, which display a quite displaced parallel arrangement, is ca. 3.5–3.6 Å, which suggests some extent of π-interactions between them. Fig. 5 Experimental (solid line) and calculated (dashed line) ECD spectra of: (a) (S,S,P)-2-(S,S,P)-3and (b) (S,S,P)-4–(S,S,P)-6in CH 2 Cl 2 in the presence of an excess of Ag(I). Organic Chemistry Frontiers Research Article This journal is © the Partner Organisations 2021 Org. Chem. Front.,2021,8,5071–5086 | 5077 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online On the other hand, the increase to seven potential binding sites for Ag(I) cations in compound (S,S,P)-3did not result in a significant increase of the chiroptical properties (Δε= +21 M −1 cm −1 ,g abs =+1×10 −2 ). In principle, a single Ag(I) cation does not need all the alkynes in the binding event, making the remaining ones useless to stabilize a second Ag(I) cation. In this situation the presence of loosely or non-bound side arms can result in a more disordered structure compared to (S,S,P)- 2, even in the presence of Ag(I). Unfortunately, the complex conformational space makes it difficult to perform any theoretical prediction. As a consequence of the previous assumption, ECD titrations showed that the compound is only bound to one Ag(I) cation with a binding constant K 3:Ag = 3.7 × 10 6 ± 15% M −1 . Minimum energy calculated structures showed that Ag(I) interacts with five alkynes. Only two alkynes remain free to bind a new cation. Our previous studies 60 indicated that two alkynes are unable to provide an efficient coordination to another Ag(I) cation. The different spatial arrangement for these two additional unbound side chains and even incavity Ag(I) displacements could explain the weaker ECD response. The presence of two additional alkynes in (S,S,P)-4should be in principle beneficial for the coordination process. Nevertheless, the ECD response remains weak and similar to the previous case (Δε= +24 M −1 cm −1 ,g abs = +0.6 × 10 −2 ). This fact suggest that at the concentrations used for the ECD experiments there is only a relevant binding constant, although subsequent Ag(I) coordination processes can take place with a modest binding constant. Accordingly, in the titration experiments a higher overall binding constant, K 4:Ag2 = 2.4 × 10 10 ± 12% M −2 , was obtained (se Fig. S129–S131†). It is worth noting that the corresponding NMR studies were carried out at much higher concentrations. Under such experimental conditions more than two equivalents of the Ag(I) cation are required to fully resolve the signals, suggesting the existence of a symmetric dimetallated structure. Compound (S,S,P)-5, presenting eleven alkynes, is able to accept two Ag(I) cations, thus yielding a longer helical structure. The first evidence came from the ECD spectra, showing a remarkable molar circular dichroism (Δε) at the longest wavelength (Δε= +85 M −1 cm −1 ,g abs = +1.7 × 10 −2 ) in the presence of an excess of Ag(I). ECD titrations also showed strong coordination of two Ag(I) cations (K 5:Ag2 =18×10 9 ± 1.6% M −2 ). This is the first example of a pure and well-defined o-OPE system presenting an enantiopure helical structure with three and a half turns. This fact shows that the chiral nucleus can be useful with the aid of Ag(I) cations in the preparation of long and conjugated helical systems. Although different situations are possible, DFT calculations showed that the energetically favored case is that in which the Ag(I) cations are separated by a distance of approximately 5.2 Å (Fig. 6f). The best chiroptical response was observed for compound (S,S,P)-6, which showed an even higher molar circular dichroism (Δε= +130 M −1 cm −1 ,g abs = +2.2 × 10 −2 ). Again, this result strongly suggests a fully folded helical structure. ECD titrations also showed three strong binding events with three Ag(I) cations (K 6:Ag3 = 2.7 × 10 17 ± 19% M −3 ). As it can be seen in Fig. 6g, DFT calculations predict a highly symmetric structure with four complete loops. The interatomic distances between consecutive Ag(I) cations are 4.4 and 4.5 Å. Interestingly, on the basis of the Ag–alkyne distances, calculations predict that the metal centers are coordinated to five alkynes. As a result, there are two alkynes that coordinate simultaneously to two Ag (I) centers, which results in longer Ag–alkyne distances (2.74–2.89 Å) in comparison with those involving triple bonds coordinated just to one metal center (Ag–alkyne distances: 2.44–2.65 Å). Fig. 6 (a) 1 H NMR spectra (400 MHz, CD 2 Cl 2 ) of compound (S,S,P)-2in the presence of 0, 1, 2, 3 and 4 equivalents of AgBF 4 . (b) Calculated structures (M06/6-31G* plus LANL2DZ for silver) in CH 2 Cl 2 for: (b) (S,S, P)-1:Ag; (c) (S,S,P)-2:Ag; (d) (S,S,P)-3:Ag; (e) (S,S,P)-4:Ag 2 ;(f)(S,S,P)-5: Ag 2 ; (g) (S,S,P)-6:Ag 3 . Color coding: C, gray; O, red; Br, wine; H, white; Ag, light blue. H atoms have been omitted for clarity. Research Article Organic Chemistry Frontiers 5078 |Org. Chem. Front.,2021,8,5071–5086 This journal is © the Partner Organisations 2021 Open Access Article. Published on 28 June 2021. Downloaded on 11/5/2021 9:45:49 AM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online VCD studies The existence of the helical structures was also confirmed by VCD spectroscopy, particularly evident when considering longer oligomers (see the ESI†). Concerning IR measurements, the presence of the Ag(I) complex results in a band shift and broadening of the feature observed at 1500 cm −1 and in the appearance of a band at 1315 cm −1 (Fig. 7). In VCD an intensification of the triplet signal at 1445, 1482 and 1493 cm −1 (+,−,+) is also characteristic of the presence of interacting Ag(I) cations, particularly considering (S,S,P)-4to 6compounds. This hints at the possibility of designing good silver switches based on IR range measurements. This (+,−,+) triplet shows similar intensity in short and long chains in the absence of silver, suggesting that the central portion of the backbone rigidified by the staple is the one responsible for this signal in all compounds. To better understand the origin of the spectroscopic changes upon silver addition, we examined two representative cases with the aid of DFT calculations: the shortest oligomer (S,S,P)-2and a longer case, (S,S,P)-5. For the first case, we considered the possible conformers and compared the calculated spectra for the most stable structures in the absence or presence of silver. The details of this analysis are given in the ESI (conformer characteristics and spectra).†Due to the staple, the structure of the short oligomer is rigid enough to present a VCD signal typical of the ordered OPE structures already observed. 60,61 In particular, the configuration of the staple dictates the prevalent helicity sense and the most stable conformer presents already the correct shape to host a silver ion; however, also partially unfolded structures of (S,S,P)-2maintain the spectroscopic pattern. In the presence of Ag(I), the calculated spectrum reproduces the wavenumber shift of the two higher energy components of the previously cited triplet (+,−,+) and the 1315 cm −1 feature intensification (Fig. 7). Also the IR spectra differences are correctly predicted. In the case of the longer oligomer, Ag(I) cations give rise to the enhancement of the triplet at 1450–1500 cm −1 . The phenomenon can be attributed to normal modes delocalized along the whole molecule, consisting of in-plane bending of the phenyl CH bonds. Structures with various Ag contents have been optimized: one central Ag ion, two Ag ions symmetrically or non-symmetrically disposed and three Ag ions (see Fig. S150†for the optimized structures and Fig. S151†for the corresponding calculated spectra). Overall, there is a good correspondence between calculated and experimental data. In fact, compound (S,S,P)-5revealed to be quite efficient in incorporating silver ions and has sufficient length to show an enhancement of VCD signals when it is guided to form a regular helix in the presence of silver. In conclusion, in the presence of silver, the longer backbone assumes an ordered structure able to show intensification of the triplet; the increase in intensity is more regular considering VCD, while ECD shows a non-monotonic dependence on the alkyne number. A complete theoretical representation of all the situations and of the two spectroscopic responses (ECD and VCD) is not easy due to the complexity of the conformational landscape and of the evident solvent effect (see Fig. 2) which is not simple to model. Chiroptical properties and CISS effect for compounds (S,S,P)-2 to (S,S,P)-6 and their corresponding Ag(I)-complexes In this vein, compounds denoted as (S,S,P)-2–6, appear to be ideal for examining the influence of the number of turns of helical molecules on their chiroptical properties and its eventual connection to the CISS effect-based spin selection power. The chiroptical properties are customarily quantified by the dissymmetry factor, g abs , of the electronic transitions. The latter quantity is expressed in terms of the extinction coefficients for left-, ε _ , and right-polarized, ε + , incident exciting light and reads as, g abs =2(ε _ −ε + )/(ε _ +ε + ) = 4(|μ||m|)cos(θ)/ (|μ| 2 +|m| 2 )≈4R/D, where Rand Dare the rotational and dipole strengths respectively for the corresponding S 0 →S n transition This equation expresses the dissymmetry factor in terms of the electric dipole transition moment, μ, and the magnetic dipole transition moment, m, and the angle subtended by these two vectors, θ. Since the magnetic dipole transition moment is normally much smaller than the corresponding electric one, one can expand (|μ| 2 +|m| 2 ) −1 in terms of powers of (|m|/|μ|) to obtain, at the first order approximation, g abs = 4(|m|/|μ|)cos(θ). On the other hand, the CISS effect translates into an additional component of the magnetic moment associated with a Rashba-like term: m CISS =α(E·(σ× p)), where ais a coupling constant, Ethe molecular electric field, σthe Pauli matrix vector and pthe linear momentum of the electron involved in the transport. This additional term has to be included in the optical response, generating, in principle, a direct connection between ECD and the CISS effect Namely, as noted above, an electron moving along the electric field in a chiral structure defined by the fixed nuclei and not by an external field, will experience in its rest frame a magnetic field, which will interact equally as above with the electron magnetic moment. Hence, the electron magnetic moment appears to be directly connected to the CISS effect. 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