CHIRALITY 26:462–470 (2014)
Strong Intermolecular Exciton Couplings in Solid-State Circular Dichroism of Aryl Benzyl Sulfoxides DANIELE PADULA,1,2 SEBASTIANO DI PIETRO,1,3 MARIA ANNUNZIATA M. CAPOZZI,4 COSIMO CARDELLICCHIO,5 1 AND GENNARO PESCITELLI * 1 Dipartimento di Chimica e Chimica Industriale, Università degli Studi di Pisa, Pisa, Italy 2 Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Prague, Czech Republic 3 Institut Nanosciences et Cryogénie, Commissariat à l’énergie atomique et aux énergies alternatives, Grenoble, France 4 Dipartimento di Chimica, Università degli Studi di Bari, Bari, Italy 5 CNR ICCOM, Dipartimento di Chimica, Bari, Italy
ABSTRACT A series of 13 enantiopure aryl benzyl sulfoxides (1a-m) with different substituents on the two aromatic rings has been previously analyzed by means of electronic circular dichroism (CD) spectroscopy. Most of these compounds are crystalline and their X-ray structure is established. For almost one-half of the series, CD spectra measured in the solid state were quite different from those in acetonitrile solution. We demonstrate that the difference is due to strong exciton couplings between molecules packed closely together in the crystal. The computational approach consists of time-dependent density functional theory (TDDFT) calculations run on “dimers” composed of nearest neighbors found in the lattice. Solid-state CD spectra are well reproduced by the average of all possible pairwise terms. The relation between the crystal space group and conformation, and the appearance of solid-state CD spectra, is also discussed. Chirality 26:462–470, 2013. © 2013 Wiley Periodicals, Inc. KEY WORDS: organic crystals; TDDFT CD calculations; pairwise additive approximation; two-body effects; intermolecular forces in crystal lattices Measurement of electronic circular dichroism (ECD, or simply CD) in the solid state1–3 is acquiring increasing importance because of some intrinsic advantages it offers with respect to its much more popular solution counterpart. The most immediate application of solid-state CD is the study of chiral condensed matter, which includes a variety of different noteworthy materials such as metal organic frameworks (MOF’s),4–9 organic gels,10–17 polymer thin films,18–20 and protein fibrils.21–23 Moreover, chiral crystallization and other chirogenic phenomena occurring exclusively in the crystalline state, which are thought to be ultimately related to the symmetry breaking observed in nature, rely on the measurement of CD and other chiroptical spectroscopies such as circular polarization of luminescence (CPL).24 These phenomena include spontaneous resolution of optically labile species,25–30 precipitation of conglomerates,31–35 and formation of co-crystals between a chiral species and an achiral or optically labile one.36–38 Our initial interest in solid-state CD spectroscopy was of a quite pragmatic nature. The very well-known sensitivity of CD to the overall molecular conformation makes this spectroscopy a valuable source of information for many stereochemical problems, but it may represent an obstacle in the assignment of absolute configurations.39,40 In fact, to reproduce the solution CD spectra of flexible compounds by means of time-dependent density functional theory (TDDFT) or other quantum mechanics methods,41,42 one first has to correctly assess the conformational ensemble in solution, and then to calculate the CD spectrum for each populated conformation. On the contrary, in the crystal state one often deals with a single, rather fixed conformation, which is possibly even known in detail — except for its absolute configuration — by X-ray crystallography. Therefore, the comparison between the solid-state CD spectrum measured on a microcrystalline sample and that calculated using the X-ray geometry as input © 2013 Wiley Periodicals, Inc.
structure would lead to the configurational assignment in a very efficient way, avoiding any conformational ambiguity. We have exploited this possibility in a so-called solid-state CD/TDDFT approach for the assignment of the absolute configuration of several organic compounds, mostly natural products.2,43–45 The advantages of this method are especially evident when very flexible and complex natural products are concerned,46 and repay well the necessary additional care to be put into solid-state CD measurements to avoid spectral artifacts.3,47–50 During the course of application of the solid-state CD/ TDDFT approach, an interesting theoretical question arose. The dense molecular packing observed in crystals, together with the geometric requisites for chiral space groups, should in principle allow for intermolecular through-space couplings to be manifested with strong exciton-coupled signals in the solid-state CD spectra. In practice, however, most of the compounds we have analyzed so far showed no apparent consequence of such couplings, even in the presence of strong aromatic chromophores. To justify this unexpected outcome, in the last years we and others have analyzed in more detail the impact of intermolecular interactions on solid-state CD spectra of organic molecules, including specific interactions such as hydrogen bonding, through-space interactions, and vibronic effects.2,51–55 Thus far, however, the heterogeneity of the cases considered did not allow us to reach any clear general conclusion about the relation between the molecular structure, the type of crystal lattice, and the appearance of solid-state CD spectra. *Correspondence to: Gennaro Pescitelli, Dipartimento di Chimica e Chimica Industriale, Università di Pisa, via Risorgimento 35, I-56126 Pisa, Italy. E-mail: [email protected] Received for publication 20 September 2013; Accepted 18 October 2013 DOI: 10.1002/chir.22270 Published online 11 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
463
EXCITON EFFECTS IN SOLID-STATE CD OF ARYL BENZYL SULFOXIDES
A few years ago, we reported a CD study on a series of aryl benzyl sulfoxides (1a-m, Scheme 1), some of which were available as single crystals and were characterized by X-ray analysis and solid-state CD.56 Contrary to the common behavior, most of these crystalline sulfoxides gave rise to substantial differences between CD spectra recorded in solution and in the solid state, pointing towards the presence of strong excitoncoupling interactions in the crystals. Moreover, we had for the first time the chance to analyze a homologous series of compounds featuring different behaviors in terms of both CD spectroscopy and crystallography. Since the original study was mostly focused on solution CD spectra, solid-state CD spectra were not extensively discussed at that time. In the CD2013 conference we presented the preliminary results of a more detailed theoretical investigation on two selected cases from the series 1a-m,57 which is fully described here. MATERIALS AND METHODS The synthesis and characterization of the whole series of aryl benzyl sulfoxides 1a-m were described in previously.56,58 Crystallographic data for all compounds are reported in Reference 58 and are deposited at the Cambridge Crystallographic Data Centre. CCDC codes for 1a and 1l are 720082 and 720089, respectively. Experimental CD spectra and crystallographic data shown in the following sections are taken from the original paper.56 Samples for the solid-state CD spectra were prepared with the KCl pellet technique3,43 by mixing
Strong Intermolecular Exciton Couplings in Solid-State Circular Dichroism of Aryl Benzyl Sulfoxides DANIELE PADULA,1,2 SEBASTIANO DI PIETRO,1,3 MARIA ANNUNZIATA M. CAPOZZI,4 COSIMO CARDELLICCHIO,5 1 AND GENNARO PESCITELLI * 1 Dipartimento di Chimica e Chimica Industriale, Università degli Studi di Pisa, Pisa, Italy 2 Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Prague, Czech Republic 3 Institut Nanosciences et Cryogénie, Commissariat à l’énergie atomique et aux énergies alternatives, Grenoble, France 4 Dipartimento di Chimica, Università degli Studi di Bari, Bari, Italy 5 CNR ICCOM, Dipartimento di Chimica, Bari, Italy
ABSTRACT A series of 13 enantiopure aryl benzyl sulfoxides (1a-m) with different substituents on the two aromatic rings has been previously analyzed by means of electronic circular dichroism (CD) spectroscopy. Most of these compounds are crystalline and their X-ray structure is established. For almost one-half of the series, CD spectra measured in the solid state were quite different from those in acetonitrile solution. We demonstrate that the difference is due to strong exciton couplings between molecules packed closely together in the crystal. The computational approach consists of time-dependent density functional theory (TDDFT) calculations run on “dimers” composed of nearest neighbors found in the lattice. Solid-state CD spectra are well reproduced by the average of all possible pairwise terms. The relation between the crystal space group and conformation, and the appearance of solid-state CD spectra, is also discussed. Chirality 26:462–470, 2013. © 2013 Wiley Periodicals, Inc. KEY WORDS: organic crystals; TDDFT CD calculations; pairwise additive approximation; two-body effects; intermolecular forces in crystal lattices Measurement of electronic circular dichroism (ECD, or simply CD) in the solid state1–3 is acquiring increasing importance because of some intrinsic advantages it offers with respect to its much more popular solution counterpart. The most immediate application of solid-state CD is the study of chiral condensed matter, which includes a variety of different noteworthy materials such as metal organic frameworks (MOF’s),4–9 organic gels,10–17 polymer thin films,18–20 and protein fibrils.21–23 Moreover, chiral crystallization and other chirogenic phenomena occurring exclusively in the crystalline state, which are thought to be ultimately related to the symmetry breaking observed in nature, rely on the measurement of CD and other chiroptical spectroscopies such as circular polarization of luminescence (CPL).24 These phenomena include spontaneous resolution of optically labile species,25–30 precipitation of conglomerates,31–35 and formation of co-crystals between a chiral species and an achiral or optically labile one.36–38 Our initial interest in solid-state CD spectroscopy was of a quite pragmatic nature. The very well-known sensitivity of CD to the overall molecular conformation makes this spectroscopy a valuable source of information for many stereochemical problems, but it may represent an obstacle in the assignment of absolute configurations.39,40 In fact, to reproduce the solution CD spectra of flexible compounds by means of time-dependent density functional theory (TDDFT) or other quantum mechanics methods,41,42 one first has to correctly assess the conformational ensemble in solution, and then to calculate the CD spectrum for each populated conformation. On the contrary, in the crystal state one often deals with a single, rather fixed conformation, which is possibly even known in detail — except for its absolute configuration — by X-ray crystallography. Therefore, the comparison between the solid-state CD spectrum measured on a microcrystalline sample and that calculated using the X-ray geometry as input © 2013 Wiley Periodicals, Inc.
structure would lead to the configurational assignment in a very efficient way, avoiding any conformational ambiguity. We have exploited this possibility in a so-called solid-state CD/TDDFT approach for the assignment of the absolute configuration of several organic compounds, mostly natural products.2,43–45 The advantages of this method are especially evident when very flexible and complex natural products are concerned,46 and repay well the necessary additional care to be put into solid-state CD measurements to avoid spectral artifacts.3,47–50 During the course of application of the solid-state CD/ TDDFT approach, an interesting theoretical question arose. The dense molecular packing observed in crystals, together with the geometric requisites for chiral space groups, should in principle allow for intermolecular through-space couplings to be manifested with strong exciton-coupled signals in the solid-state CD spectra. In practice, however, most of the compounds we have analyzed so far showed no apparent consequence of such couplings, even in the presence of strong aromatic chromophores. To justify this unexpected outcome, in the last years we and others have analyzed in more detail the impact of intermolecular interactions on solid-state CD spectra of organic molecules, including specific interactions such as hydrogen bonding, through-space interactions, and vibronic effects.2,51–55 Thus far, however, the heterogeneity of the cases considered did not allow us to reach any clear general conclusion about the relation between the molecular structure, the type of crystal lattice, and the appearance of solid-state CD spectra. *Correspondence to: Gennaro Pescitelli, Dipartimento di Chimica e Chimica Industriale, Università di Pisa, via Risorgimento 35, I-56126 Pisa, Italy. E-mail: [email protected] Received for publication 20 September 2013; Accepted 18 October 2013 DOI: 10.1002/chir.22270 Published online 11 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
463
EXCITON EFFECTS IN SOLID-STATE CD OF ARYL BENZYL SULFOXIDES
A few years ago, we reported a CD study on a series of aryl benzyl sulfoxides (1a-m, Scheme 1), some of which were available as single crystals and were characterized by X-ray analysis and solid-state CD.56 Contrary to the common behavior, most of these crystalline sulfoxides gave rise to substantial differences between CD spectra recorded in solution and in the solid state, pointing towards the presence of strong excitoncoupling interactions in the crystals. Moreover, we had for the first time the chance to analyze a homologous series of compounds featuring different behaviors in terms of both CD spectroscopy and crystallography. Since the original study was mostly focused on solution CD spectra, solid-state CD spectra were not extensively discussed at that time. In the CD2013 conference we presented the preliminary results of a more detailed theoretical investigation on two selected cases from the series 1a-m,57 which is fully described here. MATERIALS AND METHODS The synthesis and characterization of the whole series of aryl benzyl sulfoxides 1a-m were described in previously.56,58 Crystallographic data for all compounds are reported in Reference 58 and are deposited at the Cambridge Crystallographic Data Centre. CCDC codes for 1a and 1l are 720082 and 720089, respectively. Experimental CD spectra and crystallographic data shown in the following sections are taken from the original paper.56 Samples for the solid-state CD spectra were prepared with the KCl pellet technique3,43 by mixing
