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Showing papers by "J. Fraser Stoddart published in 2017"


Journal ArticleDOI
TL;DR: How being able to template the formation of mechanically interlocked molecules has led to the design and synthesis of shuttles, switches, and machines at the nanoscale is described.
Abstract: Chemistry welcomes a new bond: The mechanical bond has endowed molecules with component parts whose movements can be controlled and monitored. In his Nobel Lecture, J. F. Stoddart describes how being able to template the formation of mechanically interlocked molecules has led to the design and synthesis of shuttles, switches, and machines at the nanoscale.

615 citations


Journal ArticleDOI
TL;DR: This Review surveys the recent developments of the chemistry of naturally occurring cyclodextrins, along with a variety of synthetic flexible and rigid macrocycles that have drawn their inspiration from Pedersen's ground-breaking discovery of crown ethers in the mid-1960s.
Abstract: Macrocycles are molecular entities that display a combination of molecular recognition and complexation properties with vital implications for host–guest/supramolecular chemistry. Since the accidental discovery of the crown ethers by Pedersen half a century ago, the chemistry of wholly synthetic macrocycles for structure-specific, highly selective, host–guest complexation has experienced rapid development. While the structural diversity and host–guest chemistry of the original macrocycles are well-known, new derivatives of them are being investigated continuously and reported on today in order to improve their recognition properties as well as to unleash new opportunities in supramolecular chemistry. In this Review, we survey the recent developments of the chemistry of naturally occurring cyclodextrins, along with a variety of synthetic flexible and rigid macrocycles that have drawn their inspiration from Pedersen's ground-breaking discovery of crown ethers in the mid-1960s.

521 citations


Journal ArticleDOI
TL;DR: The different design principles by which molecular machines can be engineered to use different sources of energy to carry out self-organization and the performance of work in their environments are discussed.
Abstract: In mechanically interlocked compounds, such as rotaxanes and catenanes, the molecules are held together by mechanical rather than chemical bonds. These compounds can be engineered to have several well-defined mechanical states by incorporating recognition sites between the different components. The rates of the transitions between the recognition sites can be controlled by introducing steric “speed bumps” or electrostatically switchable gates. A mechanism for the absorption of energy can also be included by adding photoactive, catalytically active, or redox-active recognition sites, or even charges and dipoles. At equilibrium, these Mechanically Interlocked Molecules (MIMs) undergo thermally activated transitions continuously between their different mechanical states where every transition is as likely as its microscopic reverse. External energy, for example, light, external modulation of the chemical and/or physical environment or catalysis of an exergonic reaction, drives the system away from equilibrium. The absorption of energy from these processes can be used to favour some, and suppress other, transitions so that completion of a mechanical cycle in a direction in which work is done on the environment – the requisite of a molecular machine – is more likely than completion in a direction in which work is absorbed from the environment. In this Tutorial Review, we discuss the different design principles by which molecular machines can be engineered to use different sources of energy to carry out self-organization and the performance of work in their environments.

208 citations


Journal ArticleDOI
TL;DR: These composite microspheres, composed of CD-MOF nanocrystals embedded in a biocompatible polymer (PAA) matrix, constitute an efficient and pharmaceutically acceptable MOF-based carrier for sustained drug release.
Abstract: Metal–organic frameworks (MOFs), which are typically embedded in polymer matrices as composites, are emerging as a new class of carriers for sustained drug delivery. Most of the MOFs and the polymers used so far in these composites, however, are not pharmaceutically acceptable. In the investigation reported herein, composites of γ-cyclodextrin (γ-CD)-based MOFs (CD-MOFs) and polyacrylic acid (PAA) were prepared by a solid in oil-in-oil (s/o/o) emulsifying solvent evaporation method. A modified hydrothermal protocol has been established which produces efficiently at 50 °C in 6 h micron (5–10 μm) and nanometer (500–700 nm) diameter CD-MOF particles of uniform size with smooth surfaces and powder X-ray diffraction patterns that are identical with those reported in the literature. Ibuprofen (IBU) and Lansoprazole (LPZ), both insoluble in water and lacking in stability, were entrapped with high drug loading in nanometer-sized CD-MOFs by co-crystallisation (that is more effective than impregnation) without causing MOF crystal degradation during the loading process. On account of the good dispersion of drug-loaded CD-MOF nanocrystals inside polyacrylic acid (PAA) matrices and the homogeneous distribution of the drug molecules within these crystals, the composite microspheres exhibit not only spherical shapes and sustained drug release over a prolonged period of time, but they also demonstrate reduced cell toxicity. The cumulative release rate for IBU (and LPZ) follows the trend: IBU-γ-CD complex microspheres (ca. 80% in 2 h) > IBU microspheres > IBU-CD-MOF/PAA composite microspheres (ca. 50% in 24 h). Importantly, no burst release of IBU (and LPZ) was observed from the CD-MOF/PAA composite microspheres, suggesting an even distribution of the drug as well as strong drug carrier interactions inside the CD-MOF. In summary, these composite microspheres, composed of CD-MOF nanocrystals embedded in a biocompatible polymer (PAA) matrix, constitute an efficient and pharmaceutically acceptable MOF-based carrier for sustained drug release.

178 citations


Journal ArticleDOI
TL;DR: It is shown that ibuprofen can be incorporated within CD-MOF-1 either by a crystallization process using the potassium salt of ibUprofen as the alkali cation source for production of the MOF or by absorption and deprotonation of the free-acid, leading to an uptake of 23-26 wt % of ib uprofen within the CD- MOF.
Abstract: Although ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs), it exhibits poor solubility in aqueous and physiological environments as a free acid. In order to improve its oral bioavailability and rate of uptake, extensive research into the development of new formulations of ibuprofen has been undertaken, including the use of excipients as well as ibuprofen salts, such as ibuprofen lysinate and ibuprofen, sodium salt. The ultimate goals of these studies are to reduce the time required for maximum uptake of ibuprofen, as this period of time is directly proportional to the rate of onset of analgesic/anti-inflammatory effects, and to increase the half-life of the drug within the body; that is, the duration of action of the effects of the drug. Herein, we present a pharmaceutical cocrystal of ibuprofen and the biocompatible metal–organic framework called CD-MOF. This metal–organic framework (MOF) is based upon γ-cyclodextrin (γ-CD) tori that are coordinated to alkali metal c...

147 citations



Journal ArticleDOI
TL;DR: The present investigation reveals that understanding and controlling the relative conformational dispositions of redox-active units in macrocycles are key to achieving high energy density and long cycle-life electrodes for organic rechargeable batteries.
Abstract: Organic rechargeable batteries, composed of redox-active molecules, are emerging as candidates for the next generation of energy storage materials because of their large specific capacities, cost effectiveness, and the abundance of organic precursors, when compared with conventional lithium-ion batteries. Although redox-active molecules often display multiple redox states, precise control of a molecule’s redox potential, leading to a single output voltage in a battery, remains a fundamental challenge in this popular field of research. By combining macrocyclic chemistry with density functional theory calculations (DFT), we have identified a structural motif that more effectively delocalizes electrons during lithiation events in battery operations—namely, through-space electron delocalization in triangular macrocyclic molecules that exhibit a single well-defined voltage profile—compared to the discrete multiple voltage plateaus observed for a homologous macrocyclic dimer and an acyclic derivative of pyromel...

96 citations


Journal ArticleDOI
TL;DR: By taking the radical cationic state of 1,1′-dialkyl-4,4′-bipyridinium (BIPY•+) as an example, research on the art and science of introducing radical-pairing interactions into functional systems, from prototypical molecular switches to complex molecular machines is highlighted, followed by a discussion of the limitations of the current systems.
Abstract: Ever since their discovery, stable organic radicals have received considerable attention from chemists because of their unique optical, electronic, and magnetic properties. Currently, one of the most appealing challenges for the chemical community is to develop sophisticated artificial molecular machines that can do work by consuming external energy, after the manner of motor proteins. In this context, radical-pairing interactions are important in addressing the challenge: they not only provide supramolecular assistance in the synthesis of molecular machines but also open the door to developing multifunctional systems relying on the various properties of the radical species. In this Outlook, by taking the radical cationic state of 1,1′-dialkyl-4,4′-bipyridinium (BIPY•+) as an example, we highlight our research on the art and science of introducing radical-pairing interactions into functional systems, from prototypical molecular switches to complex molecular machines, followed by a discussion of the (i) li...

88 citations


Journal ArticleDOI
TL;DR: The singlet oxygen generated by the MOF/fullerene material is shown to oxidize sulfur mustard selectively to the less toxic bis(2-chloroethyl)sulfoxide with a half-life of only 11 min.
Abstract: A fullerene-based photosensitizer is incorporated postsynthetically into a Zr6 -based MOF, NU-1000, for enhanced singlet oxygen production. The structural organic linkers in the MOF platform also act as photosensitizers which contribute to the overall generation of singlet oxygen from the material under UV irradiation. The singlet oxygen generated by the MOF/fullerene material is shown to oxidize sulfur mustard selectively to the less toxic bis(2-chloroethyl)sulfoxide with a half-life of only 11 min.

86 citations


Journal ArticleDOI
TL;DR: The CO2 and H2 capture capacities of the Li+-ion-substituted CD- MOF have been shown to exceed the highest sorption capacities reported so far for CD-MOFs, a promising method for obtaining porous framework unattainable de novo.
Abstract: Co-crystallization of K+ and Li+ ions with γ-cyclodextrin (γ-CD) has been shown to substitute the K+ ion sites partially by Li+ ions, while retaining the structural integrity and accessible porosity of CD-MOF-1 (MOF, metal–organic framework). A series of experiments, in which the K+/Li+ ratio was varied with respect to that of γ-CD, have been conducted in order to achieve the highest possible proportion of Li+ ions in the framework. Attempts to obtain a CD-MOF containing only Li+ ions resulted in nonporous materials. The structural occupancy on the part of the Li+ ions in the new CD-MOF has been confirmed by single-crystal X-ray analysis by determining the vacancies of K+-ion sites and accounting for the cation/γ-CD ratio in CD-MOF-1. The proportion of Li+ ions has also been confirmed by elemental analysis, whereas powder X-ray diffraction has established the stability of the extended framework. This noninvasive synthetic approach to generating mixed-metal CD-MOFs is a promising method for obtaining porou...

70 citations


Journal ArticleDOI
TL;DR: A series of cyclophanes in which the interplanar distance between two phenyl-extended viologen (ExV2+) chromophores is varied systematically using a pair of o-, m-, or p-xylylene covalent linkers are reported, showing that the vibrational spectra of the excimer state assumes a geometry that is intermediate between that of the locally excited and CT states, approximately reflecting the degree of CT character.
Abstract: Facile exciton transport within ordered assemblies of π-stacked chromophores is essential for developing molecular photonic and electronic materials. Excimer states having variable charge transfer (CT) character are frequently implicated as promoting or inhibiting exciton mobility in such systems. However, determining the degree of CT character in excimers as a function of their structure has proven challenging. Herein, we report on a series of cyclophanes in which the interplanar distance between two phenyl-extended viologen (ExV2+) chromophores is varied systematically using a pair of o-, m-, or p-xylylene (o-, m-, or p-Xy) covalent linkers to produce o-ExBox4+ (3.5 A), m-ExBox4+ (5.6 A), and p-ExBox4+ (7.0 A), respectively. The cyclophane structures are characterized using NMR spectroscopy in solution and single-crystal X-ray diffraction in the solid state. Femtosecond transient mid-IR and stimulated Raman spectroscopies show that the CT contribution to the excimer states formed in o-ExBox4+ and m-ExBox4+ depends on the distance between the chromophores within the cyclophanes, while in the weak interaction limit, as represented by p-ExBox4+ (7.0 A), the lowest excited singlet state of ExV2+ exclusively photo-oxidizes the p-Xy spacer to give the p-Xy+•-ExV+• ion pair. Moreover, the vibrational spectra of the excimer state show that it assumes a geometry that is intermediate between that of the locally excited and CT states, approximately reflecting the degree of CT character.

Journal ArticleDOI
TL;DR: The successful preparation of hybrid ionic materials comprising macrocyclic triradical trianions with spin-frustrated ground states and accessible 1D pores offers routes to new organic spintronic materials.
Abstract: Crystalline supramolecular frameworks consisting of charged molecules, held together by hydrogen bonds and Coulomb interactions, have attracted great interest because of their unusual structural, chemical, electronic, and magnetic properties. Herein, we report the preparation, structure, and magnetic properties of the triradical trianion of a shape-persistent chiral equilateral molecular triangle having three naphthalene-1,4:5,8-bis(dicarboximide)s ((+)-NDI-Δ3(−•)). Single-crystal X-ray diffraction of its tris(cobaltocenium) salt ([(+)-NDI-Δ3(−•)(CoCp2+)3]) reveals accessible one-dimensional tubular cavities, and variable-temperature electron paramagnetic resonance spectroscopy shows that a dilute solution of [(+)-NDI-Δ3(−•)(CoCp2+)3] in an organic glass has a spin-frustrated doublet ground state and a thermally accessible quartet state. Furthermore, SQUID magnetometry from 5 to 300 K of solid [(+)-NDI-Δ3(−•)(CoCp2+)3] shows ferromagnetic ordering with a Curie temperature TC = 20 K. The successful prepara...

Journal ArticleDOI
TL;DR: The optimized artificial molecular pump operates rapidly, thanks to well-tuned noncovalent bonding interactions, paving the way to address enthalpically and entropically demanding polymers that would be difficult to obtain with the available repertoire of synthetic methods.

Journal ArticleDOI
TL;DR: Supramolecular charge-transfer cocrystals formed by electron acceptor and donor molecules that exhibit ferroelectric behavior along two distinct crystallographic axes are reported, suggesting the possibility of designing supramolescular arrays in which organic molecules support multidimensional information storage.
Abstract: Ferroelectricity in organic materials remains a subject of great interest, given its potential impact as lightweight information storage media. Here we report supramolecular charge-transfer cocrystals formed by electron acceptor and donor molecules that exhibit ferroelectric behavior along two distinct crystallographic axes. The solid-state superstructure of the cocrystals reveals that a 2:1 ratio of acceptor to donor molecules assemble into nearly orthogonal mixed stacks in which the molecules are positioned for charge-transfer in face-to-face and edge-to-face orientations, held together by an extended hydrogen-bonding network. Polarization hysteresis was observed along the face-to-face and edge-to-face axes at room temperature. The noncentrosymmetric nature of the cocrystals, required to observe ferroelectric behavior, is demonstrated using second harmonic generation measurements. This finding suggests the possibility of designing supramolecular arrays in which organic molecules support multidimensional...

Journal ArticleDOI
TL;DR: Two potential radical promoted molecular lassos were synthesized, and their different behaviour under redox stimuli shows how the molecular-level properties of analogous compounds can be affected drastically by subtle structural differences.
Abstract: Two potential viologen-based molecular lasso precursors—both composed of a 4,4′-bipyridinium (BIPY2+) unit as part of a rope appended to a cyclobis(paraquat-p-phenylene) (CBPQT4+) loop—that have been designed to mimic the threading/unthreading motion of lasso peptides, have been synthesised and characterised. Solution and solid-state experiments reveal that, when the BIPY2+ unit in the rope and the CBPQT4+ loop are connected by a bulky linker, no lasso-like conformational transformation is observed between the different redox states on account of steric effects. In sharp contrast, when the linker size is small, the molecule can be switched between (i) a free rope-like conformation in its fully oxidised state and (ii) a self-entangled lasso-like conformation under reducing conditions employing either chemical or electrochemical stimuli: the BIPY˙+ unit in the rope resides inside the cavity of the CBPQT2(˙+) loop, forming a pseudo[1]rotaxane. The switching process is reversible and stereochemically unambiguous. This research shows how tiny structural differences can induce significantly different self-complexing properties and sheds light on designing functional artificial actuators.

Journal ArticleDOI
TL;DR: The synthesis, characterization, and photophysical properties of a rationally designed multichromophoric tetracationic cyclophane, DAPPBox4+, containing a diazaperopyrenium (DAPP2+) unit and an extended viologen (ExBIPY2%) unit, which are linked together by two p-xylylene bridges are reported on.
Abstract: Molecules capable of performing highly efficient energy transfer and ultrafast photoinduced electron transfer in well-defined multichromophoric structures are indispensable to the development of artificial photofunctional systems. Herein, we report on the synthesis, characterization, and photophysical properties of a rationally designed multichromophoric tetracationic cyclophane, DAPPBox4+, containing a diazaperopyrenium (DAPP2+) unit and an extended viologen (ExBIPY2+) unit, which are linked together by two p-xylylene bridges. Both 1H NMR spectroscopy and single-crystal X-ray diffraction analysis confirm the formation of an asymmetric, rigid, box-like cyclophane, DAPPBox4+. The solid-state superstructure of this cyclophane reveals a herringbone-type packing motif, leading to two types of π···π interactions: (i) between the ExBIPY2+ unit and the DAPP2+ unit (π···π distance of 3.7 A) in the adjacent parallel cyclophane, as well as (ii) between the ExBIPY2+ unit (π···π distance of 3.2 A) and phenylene ring ...

Journal ArticleDOI
TL;DR: The extension of radical-pairing-based molecular recognition to a larger, square-shaped diradical host, [cyclobis(paraquat-4,4'-biphenylene)]2(+•) (MS2 (+•), and solid-state and computational structural analyses reveal that m-CBPQT2( +•) is ideally sized to bind inside of MS2(+.
Abstract: Persistent π-radicals such as MV+• (MV refers to methyl viologen, i.e., N,N′-dimethyl-4,4′-bipyridinum) engage in weak radical–radical interactions. This phenomenon has been utilized recently in supramolecular chemistry with the discovery that MV+• and [cyclobis(paraquat-p-phenylene)]2(+•) (CBPQT2(+•)) form a strong 1:1 host–guest complex [CBPQT⊂MV]3(+•). In this full paper, we describe the extension of radical-pairing-based molecular recognition to a larger, square-shaped diradical host, [cyclobis(paraquat-4,4′-biphenylene)]2(+•) (MS2(+•)). This molecular square was evaluated for its ability to bind an isomeric series of possible diradical cyclophane guests, which consist of two radical viologen units that are linked by two ortho-, meta-, or para-xylylene bridges to provide different spacing between the planar radicals. UV–Vis–NIR measurements reveal that only the m-xylylene-linked isomer (m-CBPQT2(+•)) binds strongly inside of MS2(+•), resulting in the formation of a tetraradical complex [MS⊂m-CBPQT]4(+...

Journal ArticleDOI
TL;DR: Electrochemical studies indicate that by replacing the BIPY2+ units in homo[2]catenane HC•7+-composed of two mechanically interlocked cyclobis(paraquat-p-phenylene) rings-with "zero", one, and two more highly conjugated diazapyrenium dication units, respectively, a consecutive series of five, six, and seven redox states can be accessed in the resulting SC·7PF6
Abstract: Radical templation centered around a heterotrisradical tricationic inclusion complex DB•+⊂DAPQT2(•+), assembled from an equimolar mixture of a disubstituted 4,4'-bipyridinium radical cation (DB•+) and an asymmetric cyclophane bisradical dication (DAPQT2(•+)), affords a symmetric [2]catenane (SC·7PF6) and an asymmetric [2]catenane (AC·7PF6) on reaction of the 1:1 complex with diazapyrene and bipyridine, respectively. Both these highly charged [2]catenanes have been isolated as air-stable monoradicals and characterized by EPR spectroscopy. X-ray crystallography suggests that the unpaired electrons are delocalized in each case across two inner 4,4'-bipyridinium (BIPY2+) units forming a mixed-valence (BIPY2)•3+ state inside both [2]catenanes, an observation which is in good agreement with spin-density calculations using density functional theory. Electrochemical studies indicate that by replacing the BIPY2+ units in homo[2]catenane HC•7+-composed of two mechanically interlocked cyclobis(paraquat-p-phenylene) rings-with "zero", one, and two more highly conjugated diazapyrenium dication (DAP2+) units, respectively, a consecutive series of five, six, and seven redox states can be accessed in the resulting SC·7PF6 (0, 4+, 6+, 7+, and 8+), HC·7PF6 (0, 2+, 4+, 6+, 7+, and 8+), and AC·7PF6 (0, 1+, 2+, 4+, 6+, 7+, and 8+), respectively. These unique [2]catenanes present a promising prototype for the fabrication of high-density data memories.

Journal ArticleDOI
TL;DR: Electrochemical studies on solid-state thin films of the macrocycle show that they exhibit semiconducting properties with a redox-conductivity of up to 7.6×10-4 S m-1 and EPR and ENDOR spectroscopies show that charge is equally shared between the NDIs within the one-electron reduced state of the NDI-based macrocycle on the time scale of these techniques.
Abstract: We report the synthesis of a tetracationic macrocycle which contains two N,N′-bis(methylene)naphthalenediimide units inserted in between the pyridinium rings of the bipyridinium units in cyclobis(paraquat-p-phenylene) (CBPQT4+ or “blue box”) and describe the investigation of its potential use in materials for organic electronics. The incorporation of the two naphthalenediimide (NDI) units into the constitution of CBPQT4+, not only changes the supramolecular properties of the tetracation in the solid state, but also has a profound influence on the electrochemical and electronic behavior of the resulting tetracationic macrocycle. In particular, the solid-state (super)structure, investigated by single-crystal X-ray diffraction, reveals the formation of a three-dimensional (3D) supramolecular framework with ca. 2.8 nm diameter one-dimensional (1D) hexagonal channels. Electrochemical studies on solid-state thin films of the macrocycle show that they exhibit semiconducting properties with a redox-conductivity of up to 7.6×10−4 S m−1. Moreover, EPR and ENDOR spectroscopies show that charge is equally shared between the NDIs within the one-electron reduced state of the NDI-based macrocycle on the time scale of these techniques.

Journal ArticleDOI
13 Sep 2017-ACS Nano
TL;DR: The results show that the balance between the stabilizing π-π interactions and the versatile Coulomb interactions dictates the elongation state of the foldamer in the gas phase and emphasizes the adequacy of mass spectrometry tools for the superstructural characterization of desolvated prototypical artificial molecular machines.
Abstract: At the interface between foldamers and mechanically interlocked molecules, oligorotaxanes exhibit a spring-like folded secondary structure with remarkable mechanical and physicochemical properties. Among these properties, the ability of oligorotaxanes to act as molecular switches through controlled modulations of their spatial extension over (un)folding dynamics is of particular interest. The present study aims to assess and further characterize this remarkable feature in the gas phase using mass spectrometry tools. In this context, we focused on the [4]5NPR+12 oligorotaxane molecule complexed with PF6– counterion and probed its co-conformational states as a function of the in-source-generated charge states. Data were interpreted in light of electronic secondary structure computations at the PM6 and DFT levels. Our results highlight two major co-conformational groups associated either with folded compact structures, notably stabilized by intramolecular π–π interactions and predominant for low charge state...

Journal ArticleDOI
13 Jul 2017-Chem
TL;DR: Jin et al. as mentioned in this paper reported the efficient synthesis of a series of Borromean rings (BRs), through which they achieved template-free BR formation with high yields in a highly controllable manner.

Journal ArticleDOI
12 Jul 2017-Nature
TL;DR: An independent experimental investigation is presented that found no evidence for ferroelectricity in one of the LASO compounds described in ref. 1 and, together with theoretical calculations, demonstrates that a possible ferro electric behaviour is not of electronic origin.
Abstract: Organic ferroelectric materials operating at room temperature are in demand in the emerging field of lightweight, flexible and environmentally friendly electronics. Tayi et al.1 reported roomtemperature ferroelectricity in organic mixed-stack charge-transfer crystals, produced using a supramolecular design concept—the lock-arm supra molecular ordering (LASO)—that synergistically combines intermolecular charge transfer and hydrogen bonds2,3. Here we present an independent experimental investigation that found no evidence for ferroelectricity in one of the LASO compounds described in ref. 1 and, together with theoretical calculations, demonstrates that a possible ferroelectric behaviour is not of electronic origin as proposed in ref. 1. We therefore question the reproducibility of the roomtemperature ferroelectricity claimed for LASO systems1. There is a Reply to this Comment by Tayi, S. A. et al. Nature 547, http://dx.doi. org/10.1038/nature22802 (2017). Room-temperature ferroelectricity has been claimed for three charge-transfer crystals formed by the same electron acceptor (A) and three different donors (D) using LASO1. The ferroelectric behaviour was ascribed to a sizeable charge ρ transferred from D to A molecules arranged in non-centrosymmetric structures characterized by polar dimers [...(D+ρA−ρ) (D+ρA−ρ)...], as observed in other mixed-stack charge-transfer crystals, albeit at cryogenic temperatures4,5. Tayi et al.1 supported their finding with a combination of structural, vibrational and dielectric measurements that we replicate here for their system 1·2 (see Fig. 1a). We note that the X-ray diffraction data of the three LASO crystals have been recently re-examined by the same authors, assigning all of them to centro-symmetric space groups3, which is incompatible with ferroelectricity. We synthesized compounds 1 and 2 and grew single crystals of compound 1·2 in different solvent mixtures under strictly anhydrous conditions. Our independent X-ray structural determination confirms the growth of the same polymorph reported in ref. 1. We also find, as in ref. 3, that a better structural refinement is obtained for the non-polar space group P1 than for the P1 group initially proposed in ref. 1. Density functional theory (DFT) calculations consistently indicate that the non-polar phases are the most stable for the three LASO compounds. Vibrational spectroscopy provides information on both electronic and structural properties of mixed-stack charge-transfer crystals6. Totally symmetric molecular vibrations offer an unambiguous probe of the dimerization of the lattice: these Raman-active modes show up in infrared spectra polarized along the stack axis only in dimerized phases, where they modulate the asymmetric flow of electronic charge, acquiring a much larger intensity than that of other vibrations. Being sensitive to local static or dynamic disorder, vibrational spectroscopy offers information complementary to X-ray diffraction data, which probes only long-range order. Our absorption infrared and Raman spectra in Fig. 1b do not present coincident peaks, firmly excluding stack dimerization, whether local or nonlocal, static or dynamic. The frequency coincidences in infrared and Raman spectra reported by Tayi et al.1 are probably accidental, owing to the presence of many bands in their limited-quality infrared spectra. We assume their infrared spectra were obtained by applying the Kubelka–Munk transformation to the singlepoint reflectance spectra of single crystals, although this transformation is appropriate only for the diffuse reflectance spectra of powders7. Infrared spectroscopy also allows us to estimate the ionicity ρ, through the frequency shift of properly chosen ‘charge sensitive’ vibrational modes, as is well established for the carbonyl (C= O) stretching of chloranil complexes8,9. Tayi et al.1 attributed sizeable charge transfer to the three LASO compounds (ρ = 0.67 for 1·2, ρ = 0.89 for 1·3 and ρ = 0.43 for 1·4), based on the frequencies of the carbonyl stretching of 1, and using a calibration procedure employing tetracyanoquinodimethane complexes that is not clear to us. The inconsistencies of this approach have been pointed out in ref. 10. Here we remark that, according to chemical intuition, experimental literature9, and DFT calculations8, the frequency of carbonyl modes is expected to decrease strongly upon negatively charging 1, and not to increase slightly, as proposed in ref. 1. Without any need of calculation or calibration, Fig. 1c compares the infrared spectra of 1 and 2 with those of the 1·2 crystal, polarized perpendicularly to the stack axis, where the C= O stretching bands appear. The spectrum of 1·2 is very similar to the superposition of the spectra of its components in the whole spectral range and specifically in the C= O stretching region, as is also confirmed by Raman spectra (see Extended Data Fig. 1). This proves that the 1·2 complex is essentially neutral (ρ ≈ 0). A similar conclusion can be drawn for the LASO compounds 1·3 and 1·4, based on the marginal shifts of the carbonyl stretching1. Hubbard model calculations10, and our DFT results (see Extended Data Table 1) further support the conclusion, pointing to largely neutral states for all three systems.