Optically Active Porphyrin and Phthalocyanine Systems - Chemical

Review pubs.acs.org/CR

Optically Active Porphyrin and Phthalocyanine Systems Hua Lu and Nagao Kobayashi* Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan ABSTRACT: This review highlights and summarizes various optically active porphyrin and phthalocyanine molecules prepared using a wide range of structural modification methods to improve the design of novel structures and their applications. The induced chirality of some illustrative achiral bis-porphyrins with a chiral guest molecule is introduced because these systems are ideal for the identification and separation of chiral biologically active substrates. In addition, the relationship between CD signal and the absolute configuration of the molecule is analyzed through an analysis of the results of molecular modeling calculations. Possible future research directions are also discussed.

CONTENTS 1. Introduction 2. Theory of Circular Dichroism 2.1. Theoretical Background 2.2. Porphyrins 2.3. Phthalocyanines 2.4. Exciton Coupling 3. Porphyrin Monomer Systems 3.1. Normal Porphyrin Systems 3.2. N-Confused Porphyrins 3.3. Heteroporphyrin Systems 3.4. Contracted Porphyrins (Corroles) 3.5. Subporphyrins 4. Porphyrin Dimer Systems 4.1. Bis-Porphyrins Formed via Chiral Linkages 4.1.1. Bis-Porphyrins Linked by Chiral Naphthalene Units 4.1.2. Bis-Porphyrins Linked by Chiral Biologically Related Units 4.1.3. Bis-Porphyrins Linked by Other Chiral Units 4.2. Bis-Porphyrins Formed via Achiral Linkages 4.2.1. Bis-Porphyrins Linked by Ethane Units 4.2.2. Bis-Porphyrins Linked by Ether Chains 4.2.3. Bis-Porphyrins Linked by Aromatic-RingRelated Units 4.2.4. Bis-Porphyrins Linked by Other Achiral Chains 4.3. Bis-Porphyrins Formed via Metal Coordination 4.4. Conformationally Rigid Systems 4.4.1. Normal Bis-Porphyrin Systems 4.4.2. Bis(N-Confused Porphyrins) 4.4.3. Meso−Meso and β−β Doubly Linked BisPorphyrin 4.4.4. Expanded Porphyrin Systems © 2016 American Chemical Society

5. Oligomeric Porphyrin Systems 5.1. Geometric Multi-Porphyrins 5.2. Multi-Porphyrins via Metal Coordination 6. Phthalocyanines with Chiral Carbons 6.1. Alkyl Chain Substituted Species 6.2. Thioether-Substituted Species 6.3. Small Aliphatic Ring-Substituted Species 6.3.1. Phthalocyanines 6.3.2. Trithiadodecaazahexaphyrin 6.3.3. Axially Substituted Subphthalocyanines 7. Phthalocyaninoids with Chiral Aromatic Substituents 7.1. Peripheral Substitution 7.2. Peripheral Substitution on Subphthalocyanines 7.3. Axial Substitution 8. Phthalocyaninoids with Geometrical Asymmetry 8.1. Phthalocyanines 8.2. Subphthalocyanines 8.3. Subnaphthalocyanines 8.4. Subporphyrazine 9. Dimeric Phthalocyanine Systems 9.1. Bis-Phthalocyanines Linked by Naphthalene Units 9.2. Bis-Phthalocyanines Linked by Coordination Interactions 9.3. Double-Decker Systems 10. Trimeric and Oligomeric Systems 11. Conclusions Author Information Corresponding Author Notes Biographies

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Received: October 6, 2015 Published: May 17, 2016 6184

DOI: 10.1021/acs.chemrev.5b00588 Chem. Rev. 2016, 116, 6184−6261

Chemical Reviews Acknowledgments Abbreviations References

Review

has the proper (chiral) mutual orientation, CD signals are often observed. The theory of CD spectroscopy will first be described, and several series of chiral Ps and Pcs are analyzed on this basis. The scope of this review only covers electronic CD, because Ps and Pcs are chromophores with absorption bands that lie across the spectrum from the near-ultraviolet to NIR regions. Chiral Ps are classified according to the number of porphyrin units, including P monomer systems, bis-porphyrin (Bis-P) systems, and oligomeric porphyrin (P) systems. Bis-P systems are further classified according to their linkage platform and conformation, such as Bis-Ps formed via chiral linkages, achiral linkages and metal coordination, plus conformationally rigid systems. The Pcs are classified according to their peripheral substituents and geometry into five different classes: (i) those with chiral carbons, (ii) those with aromatic substituents that are optically active, (iii) Pcs with geometric asymmetry, (iv) dimeric systems, and (v) oligomeric systems. Subporphyrazines (SubPzs) are considered to be Pcs because they are synthesized using a similar method to Pcs from dinitriles. Reviews on optically active Ps such as those of Kobayashi in the Handbook of Porphyrin Science (2010)80 have focused on natural P systems and the application of conformational analysis and have only contained a small amount of discussion on synthetic systems. Recent reviews on optically active Pcs such as those of Kobayashi in Coord. Chem. Rev. (2001)65 and the Handbook of Porphyrin Science (2012)81 have focused primarily on the synthesis and CD spectroscopy of Pcs from the viewpoint of organic chemistry. This review more closely examines optically active P and Pc systems as synthetic systems from the viewpoint of inorganic and physical chemistry, by placing a stronger emphasis on the relationship between molecular structure and CD spectroscopy, and, as such, will very much complement those previously written by our group. The main goal is to highlight and summarize the wide range of relevant chiral P and Pc molecular structures and their CD behavior which have been prepared with the aim of improving the design of novel structures and applications, mainly from the year 2000 to date. Some systems that are of interest from a CD analysis viewpoint are introduced, even if their CD spectra have yet to be reported or thoroughly analyzed. In particular, the induced chirality of some representative achiral Bis-P systems with chiral organic molecules is discussed because these systems are ideally suited for the identification and separation of chiral biologically active substrates.82−86

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1. INTRODUCTION As one of the most fascinating properties that exists extensively in nature,1,2 chirality has been the subject of ongoing research interest in the pharmaceutical, food, and synthetic chemicals industries.3−6 A molecule is considered to be chiral if there are two possible forms that are nonsuperimposable mirror images of each other. These structures are referred to as enantiomers (based on the Greek for opposite) or optical isomers, since they can rotate the electric and magnetic vectors of plane-polarized light in either a clockwise or counterclockwise manner.7 A large number of molecules produced by organisms exhibit a specific handedness because the response of an organism to a particular molecule often depends on how that molecule fits in a particular site on a receptor molecule in the organism. Just as the left-hand requires a left-handed glove, a left-handed receptor requires a specific enantiomer for a proper fit.8 Therefore, chirality is increasingly important, particularly in designing pharmaceuticals, because typically only one enantiomer is the active pharmaceutical ingredient that fits into the intended receptor.8 Consequently, technological developments in the synthesis, separation, and detection of chiral molecules are required.8,9 Chiral porphyrins (Ps) play an important role in biochemical systems such as the photoreaction centers (chlorophylls) in photosynthesis,10−14 biomolecular redox catalysts (cytochrome) and vitamin B12,15−17 and oxygen transport agents (hemoglobin).18−20 In particular, chlorophyll has a crucial function in photosynthesis, in which it absorbs energy from light,20 while hemoglobin in the blood carries oxygen from the respiratory organs, such as the lungs, to the body tissues, where it releases oxygen to allow aerobic respiration for powering the functions of an organism, and then carries the generated carbon dioxide back to the lungs. The chiral iron porphyrin (P) in hemoglobin helps maintain the normal shape of red blood cells.21,22 Because of their significance in many biological processes, there has been a strong research focus on chiral Ps and the preparation of synthetic biomimetic model systems in which the porphyrin moieties act as light-harvesting antennae,23−38 or as energy/ electron donors and acceptors,39−50 catalysts,51−53 and selective coordination and recognition species.54−63 The most important synthetic analogues of natural chiral Ps are chiral phthalocyanines (Pcs), which have attracted considerable attention over the last 20 years.64−69 Phthalocyanine (Pc), in which the meso carbons in porphyrin are replaced by aza linkages, have intense absorption bands at the red end of the visible region and in the near-infrared (NIR) region and thus appears to be a better artificial lightharvesting system than normal porphyrins.70−76 Circular dichroism (CD) provides a visible indicator of chirality and is defined as the difference in the absorption of left and right circularly polarized (lcp and rcp) light when an alternating beam of lcp and rcp photons generated by a photoelastic modulator interacts with a chiral molecule (i.e., ΔA = Al − Ar, where Al and Ar denote the absorption of lcp and rcp light, respectively.77−79 The observed CD signal can be either plus or minus in sign. Most Ps and Pcs are achiral molecules due to their planar structures, and no CD signals are observed. When the structures are modified by incorporating a chiral substituent at the ligand periphery to form Ps and Pcs that are referred to as extrinsically active, or molecules are intrinsically optically active due to the absence of planar symmetry, or a plurality of Ps or Pcs

2. THEORY OF CIRCULAR DICHROISM 2.1. Theoretical Background

Since CD is associated with the differential absorbance of lcp and rcp light, it is important to first introduce basic concepts of electronic absorption spectra. When chromophores are excited by an incident photon, the electron is excited to an unoccupied orbital and there is a redistribution of charge, and this results in an electronic dipole (μ). A magnetic dipole (m) can also be defined for any electronic transition. If the ground and excited states are denoted by i and j, respectively, the linear displacement of charge results in an electronic dipole transition moment, μij, while the rotation of electronic charge generates a magnetic dipole transition moment, mij. The observed absorption intensity can be derived quantitatively by integrating the spectral bands, with an x axis scale that is proportional to energy, and this value can be compared to the oscillator strength fij, which is related to the magnitude of |μij|2 + |mij|2. The electronic dipole transition 6185


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electron-withdrawing para-carboxyl group on one of the mesophenyl rings (which can be used to form a link to the hydroxyl groups of natural products), the transition dipoles still lie in the plane of the π-system and are aligned along the trans meso−meso directions, while for chlorins, which have a reduced pyrrole ring, the axes are typically aligned along the trans pyrrole−pyrrole directions. Since chlorophylls contain a fused carbocyclic ring between one of the meso positions and a pyrrole ring, the precise directions of the two dipoles must be determined using molecular orbital (MO) calculations. However, in the context of D4h or D4 symmetry metallophthalocyanines that will be described in the next section, the two lowest energy MOs are degenerate and the transition dipole moments are aligned with the trans pyrrole− pyrrole directions.

moment is usually ca. (4 to) 5 orders of magnitude greater than the magnetic dipole transition moment, for symmetry reasons. Intense absorption bands are generally said to be associated with electric-dipole allowed transitions, as is normally the case in the spectra of nonchiral aromatic molecules. In the context of chiral molecules, a magnetic dipole transition moment is also generated, and both μij and mij have nonzero values. The alignment of mij can be derived by using the right-hand rule. If the fingers adopt the direction of positive charge circulation, the thumb will be aligned with the magnetic dipole transition moment (the left hand can be used instead for the circulation of negative charge). The CD intensity, Rij, which is referred to as the rotational strength, can be derived by integrating the intensity of the CD band and is related to the scalar product of μij and mij, so that Rij = μij × mij and can have both signs, while the intensity of the absorption band is approximately proportional to |μij|2 and that of the CD band is proportional to μij × mij. Intense CD bands are only observed when either μij or mij is large, and therefore if the electronic absorption band lacks significant intensity, the CD signal is also likely to be weak. Because the bands in a CD spectrum have positive and negative signs unlike in electronic absorption spectroscopy, the overall observed rotatory strength for molecules with ground states that lack permanent magnetic dipole moments should obey the “sum rule”

2.3. Phthalocyanines

Pcs were first characterized in the 1930s by Linstead and Robertson and have been the focus of intense research interest ever since.88−91 Similar to Ps, Pcs have a square planar shape, and therefore metallo-Pcs are often approximated as chromophores of D4h symmetry, while metal-free derivatives have D2h symmetry. The introduction of bulky substituents at the α-positions results in sterically crowded structures in which the C4 axis is replaced by an S4 axis, due to their saddled D2d symmetries (Figures 2). Low-symmetry Pcs can also be prepared by using

∑R = 0 Thus, the overall integrated signal across the entire CD spectrum is zero. In many cases, however, the observed bands do not fit this relationship because significant CD intensity lies beyond the limits of what can be recorded by the available instrumentation. The “sum rule” is particularly significant in the analysis of the CD intensity associated with exciton coupling.87 2.2. Porphyrins

Metal porphyrins have an essentially square planar coordination environment and tend to adopt D4h or D4 symmetry, while the free base ligands have D2h or D2 symmetry (Figure 1). Figure 2. Chemical structure of the Pc chromophore.

phthalonitriles that do not possess C2V symmetry, since this means that the substituents on the peripheral benzene rings can be oriented in either direction with respect to the rest of the ligand. This results in the formation of four constitutional isomers with C4h, C2V, Cs, and D2h symmetry.92 Some of these may produce chiral Pcs, particularly when an axial ligand is linked. 2.4. Exciton Coupling

When there are two chromophores or more lying close to each other and absorb strongly, the electric dipole transition moments (edtms) can couple, leading to a splitting of the excited state energies to an extent that markedly modifies the spectral properties. Exciton coupling theory provides the most commonly used approach for analyzing the absorption and CD spectra of aggregated chromophore systems that are not necessarily chemically bonded. The molecular exciton model describes the coherent superposition of the excited states of aggregated systems. Because excitonic interactions typically make the largest contributions to the observed CD intensity for these systems, exciton coupling theory is particularly important for analyzing their CD spectra. Exciton coupling typically occurs when a plurality of chromophores having allowed electric-dipole transitions interact

Figure 1. Chemical structure of P chromophores and degenerate transition dipoles. In the case of meso-aryl porphyrins, one dipole runs along the 5- and 15-positions, while another runs along the 10- and 20-positions.

The symmetry can decrease further when substituents are added to the ligand periphery. The most commonly used Ps for studying chiral systems are metalated 5,10,15,20-tetraphenylporphyrins. When there are no peripheral substituents, the lowest excited state is doubly degenerate if a 4-fold axis is present. The x and y axes are typically aligned with oppositely arranged meso−meso positions in this context. When substituent groups are added to the pyrrole rings, there can be a lifting of the degeneracy of the orbitals. For example, when tetraphenylporphyrin (TPP) has an 6186


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Figure 3. Schematic exciton band energy diagrams for chromophoric dimers with various geometries. The ovals indicate a light absorbing group or molecule. The magnitude of the net electric transition dipole moments (gray) is arbitrary.

since incorrect analyses often result when they are mutually conjugated, (2) it is better to select chromophores that absorb strongly in a spectral region where there is no significant absorption by the substrate, and (3) the analysis is facilitated when a chromophore is used with a well-defined transition alignment. 5-p-Carboxyphenyl-10,15,20-triphenylporphyrin and p-dimethylaminobenzoic acid have been widely used as chromophores for these reasons. The latter has intense absorption (ε = ca. 28,000−30,000) in the 310−320 nm region, where natural products typically do not absorb, with the transition moment of the lowest energy band aligned with a permanent dipole that lies along the axis connecting the carboxyl and dimethylamino groups.96 Similarly, the Soret band of porphyrins lies in the 410−420 nm region with molar absorption coefficients as high as 5 or 6 × 105, making these chromophores useful for larger substrates where dimethylaminobenzoic acid is of limited utility.93,96 Figure 4 provides a description of the exciton coupling observed for a 1,2-diol bis(4-substituted benzoate).97 The configurations of the two carbons that the OH groups are linked to are of interest. It is noteworthy that the alignment of the transition moment that lies at lowest energy (the line connecting the carbon atom of the carboxyl group and the 4-position of the benzene) is nearly parallel to the alignment of the C−O bond in the C−OH moiety of the carboxylate group. Figure 5 provides

through space, where the independence of the chromophore is maintained. This produces a difference in the spectrum, depending on the mutual arrangement and orientation in space of the chromophores (Figure 3).93−95 When multiple chromophores are arranged in a cofacial manner, which is often referred to as H-aggregation if the constituent chromophores are numerous, the observed spectral band shifts to higher energy. Another important form of exciton coupling involves a near parallel head-to-tail alignment, which results in a shift of the spectral bands to lower energy compared to what is observed with the monomeric chromophore. When a long chain of chromophores are arranged in this manner, it is referred to as J-aggregation. A more general type occurs when the chromophores are arranged obliquely in space. Theoretically, two absorption bands should be observed at both shorter and longer wavelength, but the interchromophoric distance and the spatial arrangement of the chromophores determines whether both are clearly observed. The use of identical chromophores in a C2 or lower arrangement in symmetry terms is particularly important in the context of theoretical studies that depend on CD spectroscopy. An exciton coupling approach has been used widely to elucidate the conformation and configuration of organic compounds and natural products. When this method is applied, there are several important points to consider: (1) the component chromophores must remain independent of one another, 6187


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Figure 4. Exciton coupling between two identical 1,2-diol bis(4−substituted benzoate) chromophores (left). When viewed along the C−C bond of the 1,2-diol, molecules in which there is a clockwise twist arrangement in the alignment of the edtms of the first and second benzoate chromophores are defined as having positive exciton chirality, while those with a counterclockwise twist arrangement are defined as having negative chirality (center). The splitting of the two energy levels based on the Davydov splitting, 2Vij, results in a far larger apparent splitting of the CD spectrum (right). The minus-to-plus sequence in the CD intensity in ascending energy terms is the exciton couplet signal that is observed for systems with negative chirality. The terminology is based on the sign observed at lower energy in the bisignate CD signal. De Gruyter [Pure Appl. Chem.], Walter De Gruyter GmbH Berlin Boston, [1984]. Reprinted with permission from ref 97. Copyright and all rights reserved. Material from this publication has been used with the permission of Walter De Gruyter GmbH.

Figure 5. Typical patterns observed in the CD (right top) and electronic absorption (right bottom) spectra due to exciton coupling between two identical chromophores (bottom). The observed CD signal (solid line) is based on the differential absorbance of two component bands of opposite sign (denoted by dashed lines) separated by the Davydov splitting (Δλ). A broadening of the observed absorption band typically occurs when the Davydov splitting is significantly smaller than the band widths of the two component bands (right). For systems with positive chirality (left), a plus-to-minus sequence is observed in ascending energy terms. A minus-to-plus sequence is observed for systems with negative chirality. De Gruyter [Pure Appl. Chem.], Walter De Gruyter GmbH Berlin Boston, [1989]. Reprinted with permission from ref 98. Copyright and all rights reserved. Material from this publication has been used with the permission of Walter De Gruyter GmbH.

is exciton coupling between two benzoate moieties, there is a splitting of the excited state into two levels, but the ground state is unaffected. The energy gap between the excited state levels, Δλ, is

details on how CD spectroscopy can be used to determine the configuration of the diol by studying the bisignate exciton couplet signal observed for the lowest energy band.98 When there 6188


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edtms of the achiral core chromophore. The rotatory strength associated with this mechanism, R2, is expressed as follows:

referred to as the Davydov, or exciton, splitting. This means that there are two possible electronic transitions and hence two bands in the absorption spectrum. When the transition moments of the two chromophores do not lie in the same plane, the magnetic moment induced by the oscillation of dipole 1 is nonorthogonal with that of dipole 2. On this basis, the transitions to the two excited state energy levels have CD Cotton effect with opposite signs (Figure 5), which are separated by the Δλ (= 2 V, Davydov splitting) energy gap. When the component Cotton effects are added together, the signal has two intensity extrema. The lower energy maximum is typically called the first Cotton effect, while the higher energy maximum is referred to as the second Cotton effect. The overall amplitude of the Cotton effects can be defined as Δε1 − Δε2, where Δε1 and Δε2 are the intensities of the first and second Cotton effects at their maxima. In the absorption spectra, the two component spectral bands usually combine in a manner that results in a single broadened maximum, since the energy gap Δλ is small compared to the width of the absorption band. When the edtms of the two chromophores form a screw pattern in a clockwise manner (positive exciton chirality), in a manner similar to the dibenzoates on the right-hand side of Figure 5, the first and second CD Cotton effects have positive and negative signs, respectively. In contrast, when the two dipole moments form a screw with a counterclockwise orientation (negative exciton chirality, Figure 4), the sign sequence in ascending energy terms is negative and positive. Since the magnitude of Δλ is small, the CD spectral band has a bisignate morphology in comparison with the absorption band maximum. The amplitude of exciton couples, as defined by the peak and trough of the CD signal, is (i) inversely proportional to the distance between the chromophores squared, (ii) proportional to the squared value for the molar absorption coefficient of the chromophore, and (iii) dependent on the projection angle formed by the chromophores with minima at 0 and 180 deg and a maximum at ca. 70 degrees.99 When an optically active substituent is attached to an achiral chromophore, an induced CD (ICD) signal is often observed corresponding to the electronic absorption bands of the achiral chromophore. The “CD stealing” and “Kuhn−Kirkwood coupled oscillator” intensity mechanisms from perturbation theory have to be considered in any description of the ICD of electric dipole allowed transitions in achiral chromophores.100,101 The rotatory strength, R1, associated with the Kuhn−Kirkwood coupled oscillator mechanism is given by R1 = −K1(rj − ri)·(μj × μi )

R 2 = −K 2Im(μi ·mj)

with Im denoting the imaginary part and K2 = The mechanism is strongly dependent on the geometry, since the transition moments at the two centers must be aligned. Although coupling between the mdtms of the central achiral chromophore and the edtms of the optically active substituent is also theoretically possible, electric dipole allowed bands tend to dominate electronic absorption spectra. Thus, coupling with the edtm will typically be the easier way to obtain an intense ICD signal so that information can be readily derived about the structure of the molecule.

3. PORPHYRIN MONOMER SYSTEMS In P monomer systems, chirality can be introduced by adding covalently bound chiral substituents to the ligand or by generating a P ring with an intrinsically chiral structure. Although the synthesis of a series of chiral P monomers has been achieved, the analysis of the CD spectra has only been carried out to a limited extent and usually the spectra have been reported with no further explanation.102−107 In this section, molecular structures of representative P molecules are presented along with a brief description. The magnitude of CD is generally weak, since magnetic transition moment of monomeric aromatic molecules is zero or very small if any.77−79 3.1. Normal Porphyrin Systems

The first and simplest examples reported by the Inoue research group were shown in Figure 6.108 The “single-armed” Ps 1a−1c

(1.2)

where rj and ri are vectors describing the positions of the centers of gravity of j and i, K1 = 2πνiνjVij/h(νj2−νi2), with Vij the dipole− dipole interaction element that couples the two transitions

Figure 6. Molecular structures of single-armed Ps 1a−1c.

were considered to be distorted from planarity as a result of the steric hindrance between the meso substituent and neighboring β-position peripheral substituents. The methyl and ethyl groups on the pyrrole moieties were aligned in a single-handed manner, and thus structural antipodes were formed based on whether the amide arm was on the same or opposite sides of the P ring. Perfect mirror images were observed in the CD spectra of the two antipodes in the Soret band region. Racemization was observed via the flipping of the amide group from one side of the P plane to the other though a coplanar transition state. Subsequently, the same group extended their research using N-alkylated Ps 2a−2f with ethyl and methyl peripheral substituents (Figure 7).109,110 These molecules can form

Vij = (1/4π ϵ0){Im(μi × μj )/|rj − ri|3 − 3(μi × (rj − ri))(μj × (rj − ri))/|rj − ri|5 }

(1.4)

2νiVij /h(νj2−νi2).

(1.3)

where ϵ0 is the permittivity of a vacuum. A nonzero rotatory strength can arise for this mechanism when the electric dipole transition moments (edtms) of the substituent and chromophore are aligned in a skewed manner. The “CD stealing” intensity mechanism involves the transfer of rotatory strength from a transition of a strongly chiral peripheral substituent to the main transitions of the core ligand π-system via dipolar coupling of the magnetic dipole transition moments (mdtms) of the optically active substituent and the 6189


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Because the length and size of the strap in P 4 prohibited rotation both around the P macrocycle and within itself, the enantiomers, which were successfully resolved using chiral HPLC, were conformationally very stable and did not racemize without thermal decomposition (Figure 9).112 The CD spectra

Figure 7. Molecular structures of N-alkylated Ps 2a−2f.

enantiomers based on whether the alkyl group on the N atom is aligned upward or downward out of the P plane. Four chiral Ps were obtained due to the introduction of chiral (S)- and/or (R)-alkyl groups. The chiral strapped Ps 3a−3g shown in Figure 8 were obtained through enantiomeric resolution with a chiral HPLC column.111 Figure 9. Molecular structure of the strapped P 4.

of 4 mainly showed one couplet in the Soret absorption band region. The absolute configuration was determined through a comparison of the experimental CD spectrum and results obtained using theoretical calculations. A C2 symmetry P with two chromophore moieties added in an opposite arrangement is shown in Figure 10.113 P 5 contains two

Figure 10. Molecular structure of the naphthyl-substituted P 5.

naphthyl units with hydroxyl groups, and extraneous amino acid substituents determine the relative spatial orientation of the naphthyl moieties and the P ring through hydrogen bonding with the hydroxyl groups and Zn(II) coordination. In each case, the CD spectra of host−guest complexes contain a split Cotton effect. Meso-ABCD-type-substituted P 6 should be intrinsically chiral (Figure 11).114 Due to the significant steric interaction of the 2-hydroxy group of the naphthyl ring and the 9-hydrogen atom with the two adjacent β-hydrogens, the meso-naphthyl unit is hindered in its rotation, thus prohibiting atropisomerization. However, while the enantiomers were separated using a chiral HPLC column, their individual CD signals were undetectable, even after interaction with chiral guest molecules.

Figure 8. Molecular structures of the strapped Ps 3a−3g.

Although the relationship between the signs of the signals observed in the CD spectra and the structures of the enantiomers was not determined, the spectral data still provided an insight into intensity mechanism. Because the enantiomers had intrinsic optical activity, but had no chiral moieties, the CD signals were considered to result from interactions of the electronic dipole moments of the amido groups and those of the corresponding P rings. 6190


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Figure 13. Molecular structure of the rigid morpholinochlorin 8. Figure 11. Molecular structure of the ABCD-type-substituted P 6.

The oxophosphorous Ps 7a−7b with ethyl and methyl peripheral substituents would be expected to have intrinsic chirality since there are two different axial groups (Figure 12).115

Figure 14. CD spectra of the enantiomers of P 8 in benzene at 20 °C. Reprinted with permission from ref 117. Copyright 2004 Wiley-VCH.

Figure 12. Molecular structures of the oxophosphorous Ps 7a−7b.

An analysis of X-ray data has shown that upon addition of acid, oxo-Ps are protonated due to the formation of a cationic hydroxo complex, so that the P ring is ruffled and becomes nonplanar.116 In basic media, the planar oxo form predominates and the ethyl complex 7a has enantiomers with mirror-image monosign CD bands in the Soret band region. In acidic media, the ruffled hydroxyl form predominates and the CD intensity is enhanced significantly. A clear pH dependence is observed with the phenyl complex 7b. At basic pH, positive or negative monosignated CD bands are observed in a similar manner to the ethyl complex, while at acidic pH there are split Cotton effects. Unsubstituted tetraarylprophyrins in the ruffled conformation are achiral and have D2d symmetry. Modification at the β-carbon positions results in a lowering of the symmetry of the porphyrinoid ring, however, and this results in optically active conformers. A series of morpholinochlorins were synthesized in the presence and absence of β-carbon-to-o-phenyl linkers, and their enantiomers were successfully separated via resolution (Figure 13).117,118 As indicated by the + and − symbols shown in Figure 14, the relative positions of the carbons lie out of the mean plane of the porphyrin ring. Due to the ruffled structures, they have one of the inherent elements of chirality. The Soret and Q bands of the enantiomers lie at 442 and 660 nm, respectively, in the CD spectra with mirror-image band morphologies. Marchon and co-workers reported a series of chiro-Ps that have conformational bistability and contain methylene bridle

Figure 15. Molecular structure of the methylene bridled Ps 9.

moieties (Figure 15).119 Longer straps with n = 9−16 CH2 groups were shown to result in the formation of αβαβ conformations comprised of alternating up and down meso substituents, while the metal-free chiro-P with two 8-methylene bridles 9 (n = 8) exhibited an αααα conformation with the substituents oriented on the same side (Figure 16). In the Soret band region 6191


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Figure 16. Bridled chiroP complex as molecular nanotweezers. (Left) Open form (X-ray structure of αβαβ-NiII-8), and (right) closed form (X-ray structure of αααα-ZnII9-8). Reprinted from ref 119. Copyright 2006 American Chemical Society.

of the CD spectrum of H29-8, there is a positive Cotton effect. While in the spectrum of H29-9, which has an αβαβ conformation, there is a negative Cotton effect with a relatively small positive low-energy lobe. In a similar manner in the spectrum of the Zn(II) complexes, positive and negative Cotton effects are observed for αααα ZnII9-8 and αβαβ ZnII9-9, respectively (Figure 17d). In addition, in the Soret band region of

Figure 18. Molecular structures of N-confused Ps 10a−10b.

Figure 17. CD spectra in CH2Cl2 for the Soret transitions of (a) H2BCP-n (H29-n), (b) NiBCP-n (NiII9-n), (c) CuBCP-n (CuII9-n), and (d) ZnBCP-n (ZnII9-n). n = 8 or 9. H2BCP-8 and ZnIIBCP-8 are αααα form, while both H2BCP-9 and ZnIIBCP-9 adopt an αβαβ structure. Reprinted from ref 119. Copyright 2006 American Chemical Society.

the αβαβ NiII9-8 and NiII9-9 spectra, negative Cotton effects are observed (Figure 17b). The major spectral feature clearly correlates with the conformation in the following manner, since the αβαβ conformation gives rise to negative Cotton effects, in a manner that does not depend on the central metal and bridle length, while a positive Cotton effect is observed for the αααα conformation. The authors attributed the positive Cotton effect for αααα ZnII9-8 and H29-8 to the chiral conformation of the P chromophore and the negative Cotton effect for αβαβ NiII9-8 to the magnetic-electric coupling of the Soret and n-π* carbonyl bands, while the small low-energy positive component that is observed for H29-9 and ZnII9-9 was proposed to be due to a contribution related to intrinsic chirality.

Figure 19. UV−vis (lower trace) and CD spectra (upper trace) in CH2Cl2 for (S)-10a (solid line) and (R)-10a (dashed line). Reprinted with permission from ref 121. Copyright 2011 Wiley-VCH.

In addition, the molar amplitudes Δε of these signals were three times higher than the CD signals in the spectra of the respective enantiomers of the parent complexes. Further modifications of NCPs are relatively simple to accomplish because the confused pyrrole has three sites with differing reactivities (N2, external nitrogen; C3, external carbon; C21, internal carbon), and each site can be targeted for addition or substitution reactions. The resulting systems are typically chiral due to their distorted, rigid conformation.122,123 For example, Liu and co-workers reported NCP 11 which contains a CO bridging link between the internal C21 carbon with one of the internal nitrogen atoms (Figure 20).124 The corresponding enantiomers were successfully separated, and their CD signals were mirror images over the entire absorption region (Figure 21). The molecule was used to enable chiral recognition of optically

3.2. N-Confused Porphyrins

N-confused Ps (NCPs) are similar to the parent P macrocycle, but have a carbon atom at one of the coordinating pyrrolic positions, since the nitrogen atom lies at what would normally be a β-pyrrolic site on the periphery of the ring.120 Recently, Chmielewski and co-workers reported a series of NCPs bearing substituents on the internal carbon (C21) (Figure 18).121 The nonplanarity of the system results in chirality, due to the trigonal hybridization of internal carbon atom C21. The CD spectra of the enantiomers of 10a contain Cotton effects in the Soret band region at ca. 450 nm with perfect mirror images (Figure 19). 6192


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Figure 20. Molecular structure of an N-confused and C = O-bridged P 11. Figure 22. Molecular structures of hetero-Ps 12a−12d.

Figure 23. CD spectra recorded for enantiomers of 12d in DCM at 298 K. Reprinted from ref 125. Copyright 2013 American Chemical Society. Figure 21. CD spectra of the enantiomers of 11; 1, first fraction (R configuration) and 2, second fraction (S configuration). Reprinted from ref 124. Copyright 2014 American Chemical Society.

C2v symmetry compared to those of P.126,127 The first chiral N-substituted corrole was investigated in 1999.128 Recently, Churchill and co-workers reported a chiral metallocorrole complex 13 with different meso-substituents (Figure 24).129 Since there are

active alcohols and acids due to the nucleophilic nature of the external nitrogen atom, which acts as a hydrogen bond acceptor. Under acidic conditions, there is slow racemization. Timedependent density functional theory (TD-DFT) calculations were performed so that the DFT-optimized structure of the R-enantiomer could be determined and the absolute configuration could be assigned. It was found that the first fraction eluted from the HPLC column, which had positive signs for the Cotton effects in the Soret and Q-band regions, had the absolute configuration R. An attempt made to determine the absolute configuration assignment by using an X-ray crystal structure analysis was not successful, because enantiopure crystals underwent racemization resulting in pseudosymmetry due to the inversion center within the centrosymmetric space group P21/c. 3.3. Heteroporphyrin Systems

More recently, Latos-Grażyński and co-workers reported helical hetero-Ps 12a−12d that contain 1,5-naphthylene groups (Figure 22).125 Here, the substitution mode of 1,5-naphthylene building block imposes steric constraints on the structure and this determines the helical conformation. CD experiments demonstrated the complementary optical activity of the enantiomers (Figure 23). In addition, the enantiomers were stable in optical terms and there was no evidence of racemization because the naphthylene group blocked the conversion of the structural conformation.

three different substituents on the corrole ring (i.e., no rotation axis) and an axial oxo ligand, the two enantiomers originating from upward and downward oxo ligation to the Cr center were clearly observed in the crystal structure of a racemic mixture. However, separation of the enantiomers was reported to be quite difficult.

3.4. Contracted Porphyrins (Corroles)

3.5. Subporphyrins

Corrole is an 18-π electron tetrapyrrolic macrocycle containing a direct pyrrole−pyrrole linkage with a smaller cavity and lower

Recently, Osuka and co-workers designed the first B-phenylated ABC-type chiral subporphyrins (SubPs) (Figure 25).130 Because

Figure 24. Molecular structure of ABC-type corrole 13.

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Figure 25. Molecular structures of ABC-type SubPs 14a−14b.

based on induced CD spectroscopy, if they are introduced properly to another chromophore, such as a P. Hayashi and co-workers prepared the Bis-P 15 by linking two ZnPs to a chiral (S)-BNP unit (Figure 26)136 and demonstrated

SubPs adopt a bowl-like structure, ABC-type SubPs should be chiral if there is no flip-flop bowl inversion. However, the enantiomeric separation of B-methoxy SubPs was not successful due to facile flip-flop bowl inversion through SN1-type heterolysis, which leads to racemization. The enantiomers of B-phenylated 14a and 14b were, however, successfully separated using a chiral HPLC column. They were found to display a weak Cotton effect, probably because the chirality originated from the different directional arrangements of the peripheral aryl substituents, which can rotate to form 8 possible conformers with each showing quite different Cotton effects, leading to their near cancelation.

4. PORPHYRIN DIMER SYSTEMS The amplitude of a CD exciton couplet is both proportional to the square of the extinction coefficients of the coupled chromophores and inversely proportional to the square of the distance between them.131,132 It follows from this that intense absorption results in intense CD signals. In order to minimize complications that arise from the overlap of chromophores in the substrates, which is particularly important for biochemical samples, it is best to avoid the 280 nm band that arises from nucleic acid bases, proteins, or impurities, so significant effort has focused on developing highly sensitive chromophores with red-shifted bands that are suitable for use with amino, hydroxyl, and other groups.131 Ps, typically tetraphenyl porpyrin derivatives, are ideal chromophores for investigating CD exciton couplets and offer many advantages, such as (I) the spectra of Ps are dominated by intense and narrow Soret bands at ca. 410 nm, and this usually eliminates the possibility of an overlap with other bands; (II) the strong absorption coefficients of Ps typically exceed 5 × 105; (III) the intense absorption leads to throughspace coupling over long distances; and (IV) versatile structural modification of Ps is possible.131 Therefore, Bis-Ps have been developed to extend the applicability of the exciton coupling method to configuration studies of molecules and to conformational research on biopolymers.85,133 Pcs are not used for this purpose, since the electric transition moment in Pc generally does not pass the position of substituent.

Figure 26. Molecular structure of BNP-linked Bis-P 15.

that this system can be used to form a ditopic coreceptor for several different diamines. The CD spectra of complexes with alkyl groups of various chain lengths connecting the terminal amino groups were measured. When diamines are not present, a plus-to-minus sign sequence is observed in the CD spectrum of the Bis-P 15 in the longer wavelength and Soret band regions, since (S)-BNP is right-handed in conformational terms. Upon addition of diamines, the Zn ions are coordinated by two amino groups resulting in a change in the angle formed between the two Ps. The largest complexation constant was obtained with 1,8-diaminooctane along with the most intense bisignate signal, and the two Ps maintained a right-handed helicity. Kimura and co-workers reported the synthesis and CD spectroscopy of Bis-Ps with (S)- and (R)-BNP-linker moieties 16 (Figure 27).137 In the Soret band region, the metal-free derivative displayed bisignated CD bands. In the CD spectrum of the R-enantiomer, a positive sign is observed at 427 nm, where the Soret absorption band lies, along with a negative sign at higher energy. Notably, when a central Fe(II) was added to form a metal complex, the intensity of the bisignate CD signal descreased to almost zero, with a positive CD signal observed in the Soret region for the R-enantiomer. This implies that the CD signal in this region was the result of CD intensity induced by the coupling interaction between the BNP unit and the P chromophore. BNP-linked Bis-P 17 was reported by Ema and co-workers (Figure 28).138,139 In this case, two BNP moieties were introduced

4.1. Bis-Porphyrins Formed via Chiral Linkages

4.1.1. Bis-Porphyrins Linked by Chiral Naphthalene Units. Chiral 1,1′-binaphthyl (BNP) derivatives have been extensively used for asymmetric catalysis, molecular recognition, and to provide novel materials in a variety of different systems.134,135 In addition, 1,1′-BNP derivatives can be used to perform analyses 6194


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Figure 27. Molecular structure of (R)/(S)-BNP-linked Bis-P 16.

to force the two P rings to form a chiral Bis-P, resulting in the formation of a macrocyclic cavity which can interact with guest molecules. Although the chiroptical properties were not investigated, the chiral functionality was introduced to enable chiral discrimination of aromatic compounds with electrondeficient properties that incorporate a dinitrophenyl ring via cooperative double π−π stacking interactions. Two Ps can be introduced onto the terminal naphthalene units of 1,1′-position-linked optically active naphthalene dimers and oligomers (Figure 29).140 The largest example of this kind of system containing an octamer of binaphthyl consisting of 16 naphthalene units linking two TPP groups exhibited a coupled CD intensity in the Soret band region of the TPP spectrum (Figure 30). More intriguingly, there was a very close correlation between the chirality and the intensity of the coupled signals. It was concluded by examining X-ray data for several oligomers, together with semiempirical molecular modeling calculations, that on average, the adjacent naphthalene moieties formed dihedral angles ranging from 74.7 to 113°, with the average of 90.02°. If this analysis is correct, upon linking four (S)-naphthalene moieties, two Ps should be orientated in a counterclockwise direction (Figure 31), which results in a negative exciton-coupling. In contrast, if they are linked through naphthalene units with one R- and two S-configurations then the P rings are orientated in a clockwise manner, and a positive split signal is anticipated. Moreover, the intensity of the CD band can be assumed to be

Figure 29. Molecular structure of di- and oligo-BNP-linked Bis-Ps 18.

inversely proportional to the square of the interchromophoric distance. Since the naphthalene moieties are linked in a linear manner and the distance between the porphyrin rings can easily be estimated, this system is ideal for exploring the relationship between chirality and CD intensity. 4.1.2. Bis-Porphyrins Linked by Chiral Biologically Related Units. Since various functional biomolecules such as hemes, chlorophylls, and vitamin B12 contain Ps and related compounds as their active centers, the importance of biologically related units linked with Ps is increasing. These kinds of systems are useful as models for alternatively functionalized natural biomolecules which may have promising properties for application as chiral molecular receptors.35,141−144 Peptides have often been used to provide optically active backbones for linking P rings. For example, the Bis-P 19 consists of two P rings linked to the natural peptide Gramicidin S, which has a cyclic structure (Figure 32).145 Because of the side-by-side orientation of the P rings and the left-twisted polypeptide

Figure 28. Molecular structure of bis(R)-BNP-linked Bis-P 17. 6195


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Figure 30. Structure of two tetraphenylporphyrins (TPP) linked by hexadecanaphthalene on the upper and lower naphthalene rings. Reprinted from ref 140. Copyright 2006 American Chemical Society.

Figure 32. Molecular structure of peptide-linked Bis-P 19.

Aida and co-workers prepared cyclic hosts 20−21, which consists of two ZnP rings connected by an oligo(aminoisobutyric acid) (Aib) linker (Figure 33).146 Due to the limited flexibility of the covalent bridges and their long length, the host has a highly specific response for chiral bis-pyridyl-substituted guest molecules of suitable length resulting in stable 1:1 inclusion complexes. The inclusion complex 20·L-G1 has a strong exciton couplet in the Soret band region of the P moieties (410−450 nm) (Figure 34a, solid curve). The CD spectrum (broken curve) of 20·L-G1 exhibits mirror symmetry with that of 20·D-G1. The chirality of the guest molecule is transferred effectively to the Bis-P hosts, due to the strong exciton coupling in Soret band region. It is noteworthy that the exciton couplets of 21·G1 are less intense than those observed for 20·G1, and its CD spectrum differs in the high-energy region. The obvious explanation is the overlap with the CD band associated with the meso-aryl groups and the phenyl-rings of the oligopeptide pillars. If the CD spectrum of 20·G1 (Figure 34a) is subtracted from that of 21·G1 (Figure 34b), a differential spectrum is obtained, which is almost identical to the CD spectra of single-handed phenyl-containing oligopeptides.147 Soon after this, the same authors reported the preparation and properties of two P rings arranged in a helical conformation by introducing two chiral strap linkers with leucine residues (Figure 35),148 resulting in exciton couplets corresponding to the P absorption bands. Incorporation of D- and L-leucine derivatives results in left- and right-handed orientations, respectively, and

Figure 31. Application of the exciton chirality method to oligonaphthalene skeletons. Reprinted from ref 140. Copyright 2006 American Chemical Society.

backbone, there is a relatively intense negative couplet in the CD spectra of all of these compounds. In the CD spectrum of the dizinc complex 19, the intensity of the signal depends on the solvent and the highest intensity is observed in toluene, which is in accordance with the supramolecular chirality concept, which states that the solvent actively participates and can hence directly influence the chirality of the system. The variability associated with the solvation environment reflects the structural flexibility of the P rings in conformational terms. When 4,4′-dipyridyl is involved, however, the complexity of the CD band is considerably increased, with the major positive peak at 424 nm, the intensity of which is strongly diminished as a result of the nearly parallel mutual orientation of the two Ps. 6196


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Figure 33. Molecular structures of poly(Aib)-linked Bis-Ps 20−21 and their chiral guests.

red-shifted but with a significantly lower signal enhancement. This indicates that the twisted arrangement of the ZnP rings is probably stabilized by the inclusion of an energetically favored guest molecule in its cavity to form a peptide bundle. It is noteworthy that a larger enhancement of the CD signal was also observed when L-22 or D-22 was mixed with racemic guest rac-G2 (Figure 36). This suggests that the optical resolution of rac-G2 occurs in solution due to the selective binding of 22 under competitive conditions. The supramolecular chirality of 22 was then used to enable the optical resolution of a series of synthetic oligopeptides (OPs) with bidentate properties, achieving enantiomeric excesses (ees) as high as 80%. Because the CD signals for the different enantiomeric forms of DNA lie in the spectral region below 300 nm, determination and

provided perfect mirror-image CD spectra. The corresponding supramolecular host−guest (L- and D-22) interactions also results in stable 1:1 complexes. The large difference in the association constants Kassoc(L⊃L) of 14.2 × 106 M−1 and Kassoc(L⊃D) of 2.9 × 106 M−1 indicates that host L-22 (which has left-handed helicity) has a much greater affinity toward the left-handed guest L-G2 than right-handed D-G2. Accordingly, complexation of D-22 by the right-handed D-G2 structure is favored over the left-handed L-G2 structure (Figure 36). In addition, the exciton-couplet in the Soret band region for the main ZnP transition shifts to the red from 424 to 431 nm and significantly enhanced for the inclusion complex of L-22 with L-G2, whereas the CD signal for a mixture of L-22 with the less favorable left-handed D-G2 structure (10 equiv) was also 6197


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Figure 34. (a) CD spectra of 20 (red) and 21 (blue) in the presence of L-G1 (solid curves) and D-G1 (broken curves) ([guest]/[host] = 1.0) in CHCl3 at 25 °C. (b) Differential spectra obtained by subtracting the CD spectrum of 20·L-G1 from that of 21·L-G1 (solid curve) and 20·D-G1 from that of 21·D-G1 (broken curve). Reprinted from ref 146. Copyright 2004 American Chemical Society.

sensing of DNA configurations can be hindered by the concomitant presence of both forms and/or other biomolecules, such as proteins, which also have CD bands that lie in the UV region beyond 300 nm.149 In order to solve this problem, it is desirable to design chiroptical probes that discriminate between the E and Z structures, absorb above 300 nm, and provide characteristic ICD signals. The exciton couplet that results from the Bis-P structure makes the P rings ideal for use as chiroptical probes for CD structural studies. Berova and co-workers investigated in detail the CD profile within the P Soret band region of DNA linked Bis-Ps in order to determine the DNA conformations.149−153 4.1.3. Bis-Porphyrins Linked by Other Chiral Units. Two P units can also be linked by other flexible chiral groups for application to asymmetric catalysis and chirality sensing. The flexibility of the host in conformational terms facilitates the binding of a wide range of chiral molecules.154,155 Sakai and co-workers reported a Bis-P system with a chiral benzoate bridge (Figure 37).156 In the Soret band region, the resulting double-strapped complex exhibited oppositely signed Cotton effects of low intensity. Upon interaction with diamines, the CD signals were considerably increased, since the exciton coupling between the two P rings is enhanced. However, the binding of chiral monoamines did not affect the CD signal amplitude. This result indicated that the binding of diamines resulted in a rigid conformation for the two P rings. It is noteworthy that the chirality of the diamines G4 and G5 determines the sign sequences for the observed exciton couplets (Figure 38, panels c and d), while for diamines G6 and G7, the chirality of 23 was the key factor in determining the signs of the CD signals. The CD intensity was also affected to a significant extent by the structure of the diamine and its chirality. Therefore, because of the flexible structure of bis-Ps, its conformation could be easily adjusted to accommodate the chirality and of guest diamines of differing sizes.

Figure 35. Molecular structure of the helical poly(Aib)-linked Bis-P 22.

Recently, a Bis-P linked by the chiral group (−)-2,3,-Oisopropylidene-D-threitol was prepared in 95% isolated yield using bromoporphyrin and a combination of the Xantphos ligand and Pd2(dba)3 as the catalyst (Figure 39). The high effectiveness of the coupling reaction is particularly notable.157 The chiral properties of these Bis-Ps were not explored, however. 4.2. Bis-Porphyrins Formed via Achiral Linkages

Bis-Ps containing achiral linkages are considered to be some of the most useful chromophores for using exciton coupling circular dichroism (ECCD) spectroscopy to determine the absolute configuration of chiral substrates.133 In the visible 6198


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Figure 36. Complexation of 22 with the guest G2 at [G2]/[22] = 10:1 in CHCl3 at 25 °C. (a) CD spectra of L-22 in the absence (black curve) and presence of L-G2 (blue curve), D-G2 (green curve), and rac-G2 (red curve). (b) CD spectra of D-22 in the absence (black curve) and presence of D-G2 (blue curve), L-G2 (green curve), and rac-G2 (red curve). Reprinted from ref 148. Copyright 2004 Wiley-VCH.

Figure 38. CD spectra of (R,R)-23 (red) and (S,S)-23 (blue) (a) before and (b) after addition of achiral diamine 7 (2.5 equiv) in CHCl3. CD spectra of (R,R)-23 in the presence of (R)-diamine (red) and (S)-diamine (pink) and (S,S)-23 in the presence of (R)-diamine (blue) and (S)-diamine (green): (c) G3 (50 equiv), (d) G4 (2 equiv), (e) G5 (1.6 equiv), and (f) G6 (10 equiv). Reprinted from ref 156. Copyright 2005 American Chemical Society.

Figure 37. Molecular structures of chiral benzoate-linked Bis-P 23 and guests G3−G8.

region, the intense Soret band provides the basis for their satisfactory chirogenic performance. In the free base form, they lack chirality and are therefore CD-silent. Upon mixing with a chiral guest (usually bidentate), such as amino, hydroxyl, or carboxyl compounds, the host (Bis-P) undergoes ditopic coordination, which is stereocontrolled by the chiral guest. The two P chromophores become mutually twisted and adopt a single preferred sense of chirality because they encompass the guest in the binding pocket. Therefore, the complex displays a very intense exciton split CD band within the Soret band region at approximately 420 nm, which can be readily analyzed to determine absolute configuration of the guest molecule.158

Figure 39. Molecular structure of the chiral isopropylidene-D-threitollinked Bis-P 24.

4.2.1. Bis-Porphyrins Linked by Ethane Units. Inoue, Borovkov, and co-workers reported the use of an achiral Bis-P (25, Figure 40) comprised of two octaethylporphyrin rings with a flexible ethane bridge linked at the meso-carbon positions to determine the absolute configuration of chiral substrates.159−173 The authors clearly demonstrated that the temperature, solvent effects, stoichiometry, and structure of the chiral guest ligand can be used to control the supramolecular chirality.159−174 6199


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Figure 40. Molecular structure of flexible ethane-linked Bis-P 25.

For example, they studied systematically the thermally driven chirality in the system using variable-temperature (VT) CD in the presence of chiral guests.159 When the guest molecules are enantiopure, the achiral syn folded conformer of Bis-P 25 gradually transformed into the extended chiral anti conformer as the temperature was decreased from 293 to 183 K (Figure 41).

Figure 41. Mechanism of thermally induced supramolecular chirality in a Bis-P. Reprinted from ref 159. Copyright 2000 American Chemical Society.

Figure 42. Temperature-induced changes in (a) the CD spectrum and (b) UV−vis spectrum of Bis-P 25 in CH2Cl2 containing (S)-(−)-1PhEtNH2 upon cooling from 293 to 183 K (solid lines) or (R)-(+)-1PhEtNH2 at 183 K (dotted line in the CD and UV−vis spectra is coincident with that of the (S)-enantiomer). Reprinted from ref 159. Copyright 2000 American Chemical Society.

This syn-anti conformational switching was also confirmed using VT UV−vis spectroscopy (Figure 42b). In The UV−vis spectrum, the anti conformer exhibited bathochromically shifted, well-resolved B⊥ and B// bands. VT CD spectra recorded during the change in conformation contained oppositely signed Cotton effects which gradually increased in intensity with decreasing temperature. The maximum and minimum positions for the exciton couplets were associated with the B⊥ and B// absorption bands, respectively. There was a close match between the 12−14 nm splitting that was observed in the CD spectrum (ΔECD) and the Davydov splitting, which was derived from the absorption spectrum of the anti conformer. This demonstrates that the achiral syn form changes into the chiral supramolecular anti conformer when optically active ligands are present at low

temperature. This process can be explained as follows: with decreasing temperature, the formation of the anti form occurs due to ligation of a ZnP ring with a chiral ligand; a second (R)- or (S)-enantiopure ligand then coordinates the second ZnP ring to form a bis-ligated structure, so that the anti structure contains chiral ligands on the same side of the P rings. This arrangement triggered a change in the conformation of the neighboring P rings in the Bis-P to form anti conformers with left- or right-handed screws (Figure 41). The structure of the chiral guest played a vital role in the induction of the chirality. The origin of the supramolecular 6200


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chirogenesis is related to screw formation in Bis-P 25, with the direction determined by the absolute configuration of the amine guest molecule. (S)-enantiomers induced positive chirality, since a right-handed screw is formed, while (R)-enantiomers result in the formation of a left-handed screw due to negative chirality.159,160 The screw magnitude was also largely dependent on the structure of the amine guest molecule (Figure 43).

Figure 44. CPK molecular models and coupling electronic transitions for supramolecular chirality induction and inversion in achiral syn 25 by (R,R)-DPEA. Reprinted from ref 161. Copyright 2002 American Chemical Society.

chirality, while high molar excess results in a 1:2 anti complex with an extended left-handed structure. In addition, the Soret absorption band intensity of syn 25 gradually decreases when DPEA was added, and new split red-shifted bands are observed at low ligand molar excesses for exciton coupled B⊥ and B// bands of (R)-G3·25 (Figure 45a). Furthermore, when (R,R)-DPEA is

Figure 43. CD spectra of Bis-P 25 in CH2Cl2 containing (R)-(+)-1PhEtNH2 (solid line), (R)-(−)-2-BuNH2 (dotted line), and (R)-(+)-1PhEtOH (dashed line) at 193 K. Reprinted from ref 159. Copyright 2000 American Chemical Society.

When amines with larger side groups are involved, there is an intensification of the CD signals. Amines were found to have larger affinities than alcohols, while primary amines bind more strongly than secondary amines. In addition, aromatic ligands bind more weakly than aliphatic ligands, but larger aromatic rings have larger binding strengths. Hence, it can be concluded that the supramolecular chirogenesis depends to a significant extent on the structure of the optically active guest molecule, and this is related to the absolute configuration of the guest, the bulkiness in the steric terms at the chiral center, and the nature of the binding group and the binding site’s position with respect to the asymmetric carbon atom. Another factor which affected the supramolecular chirogenesis in this host−guest system was the ligand stoichiometry. The amount of excess ligand has a significant impact on the transfer of the chirality information from the guest molecule to the achiral host (Figure 44).161 For example, chirality inversion was found to occur when there is an interaction with (R,R)diphenylethylenediamine [(R,R)-DPEA, (R)-G3]. At low molar excess, this results in a 1:1 tweezer complex with right-handed

Figure 45. Changes in the CD and UV−vis spectra of 25 upon addition of the guest (R,R)-DPEA at (a) low (1:0.12 to 1:16.5) and (b) high (1:112 to 1:4866) ligand molar excesses. Reprinted from ref 161. Copyright 2002 American Chemical Society.

selected, there is a stepwise intensity enhancement in the Soret band region for the bisignate Cotton effects upon addition of DPEA, which was attributed to the induced chirality in (R)-G3·25 following the formation of a right-handed twist. When (S,S)-DPEA is selected, however, the alignments of the 6201


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Scheme 1. Structures and Equilibria for Bis-P 25 in the Presence of Bidentate Guests

Figure 46. ORTEP-3 representation of (R)-G4·25. Heavy atoms are shown as 50% probability ellipsoids. The crystallographic numbering excludes the peripheral ethyl groups and all H atoms for clarity. The arrow indicates the noncrystallographic pseudo-2-fold axis. Reprinted with permission from ref 165. Copyright 2003 Wiley-VCH.

Figure 47. Experimental MCD, CD, and absorption spectra recorded in CH2Cl2 at room temperature (left) and the calculated CD and absorption spectra (right) of the B-band region of the (R)-G4·25 tweezer. Each calculated exciton band was described using a single Gaussian curve. The notations plus and minus represent the in-phase and out-of-phase transitions, respectively. Reprinted with permission from ref 165. Copyright 2003 Wiley-VCH.

coupled dipoles in the tweezer moiety were exactly opposite, and this results in negative chirality. In the Soret band region at 438 nm, the first Cotton effect is closely aligned to the most red-shifted absorption band which arose from the lowest energy B∥ coupling transitions. On the other hand, the addition of a large excess of (R,R)-DPEA results in significant changes in the CD and absorption spectra (Figure 45b) since there is a stepwise shift in the equilibrium toward 1:2 complex formation. Correspondingly, red-shifted bands were observed at 421 and 436 nm with increasing intensity, while the higher energy band at 411 nm shows a decrease in intensity, due to formation of the extended structure of anti [(R)-G3]2·25. The anti [(R)-G3]2·25 structure has a left-handed twist that minimizes steric hindrance that results from the interaction between the P ethyl group, and Ph(NH2)CH, which is the bulkiest substituent of (R,R)-DPEA. On this basis, a coupling of the B∥ transitions form a counterclockwise twist resulting in negative chirality in the context of an exciton chirality analysis (Figure 44).

Subsequently, the binding behavior and complexation properties for supramolecular chirality resulting from the presence of optically active bidentate guests, such as amino alcohols and diamines, were investigated.166 The majority of geometrically suitable bidentate guests exhibited two major equilibrium steps (Scheme 1): with the first ligation (K1) process resulting in a host−guest (1:1) tweezer structure and the second ligation (K2) resulting in an anti bis-guest structure (1:2) (Scheme 1). The first ligation process is much stronger, and the binding strengths depended on which ligand was present and the nature of its functional groups. Enhanced conformer stability and optimal tweezer complex geometry ensured that the chirality information was efficiently transferred 6202


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Figure 48. Molecular structure of the flexible ethane-linked Bis-P 26.

Figure 51. Experimental absorption (bottom) and CD (top) spectra of (R,R/R,R)-27 (1a) and (S,S/S,S)-27 (1b) in CH2Cl2 at room temperature. Reprinted from ref 169. Copyright 2005 American Chemical Society.

Figure 49. CD spectra of 26 in the presence of a chiral guest in CH2Cl2. Reprinted from ref 171. Copyright 2007 American Chemical Society.

Figure 52. (a) Calculated absorption and CD stick spectra of (R,R/R,R)-27 based on the optimized structure. The notations (+) and (−) represent the in-phase and out-of-phase transitions, respectively. (b) Computed linear absorption spectrum of 27. Reprinted from ref 169. Copyright 2005 American Chemical Society.

Figure 50. Molecular structure of flexible ethane-linked chiral bischlorin 27. 6203


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Figure 53. Molecular structures of flexible ether-linked achiral Bis-Ps 28 and 29.

Figure 54. Molecular structure of the flexible ether-linked achiral Bis-P 30.

attributed to the lower energy B// exciton coupling band. In addition, the sign associated with the first Cotton effect depends on the absolute configuration of the optically active ligands, so the (S,S)-enantiomer of DACH induces positive chirality, while the antipodal (R,R)-DACH results in negative chirality. Interestingly, the CD signal of the 1:1 tweezer complex was also observed in the solid state. Interestingly, the crystallographic structure of (R)-G4·25 was obtained (Figure 46).167 In the absorption spectrum, the

to the achiral host from the chiral guest, inducing supramolecular chiral properties. When 1,2-diaminocyclohexane (DACH, G4) was used that was enantiopure, a chiral 1:1 tweezer was exclusively formed, regardless of the ligand concentration.163 The tweezer is highly optically active in the solid state and in solution (even when photoexcited). Its CD spectrum contains Cotton effects in the Soret band region of P, with the first effect at 436 nm closely aligned with the most red-shifted absorption band, which was 6204


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Figure 55. Molecular structure of the flexible ether-linked achiral Bis-P 31.

Figure 56. Molecular structure of flexible ether-linked achiral Bis-P 32.

than the extra coordination mode that occurs in metallo complexes. The parent syn-26 structure is not optically active; however, when enantiopure acids are present, significant CD intensity was observed in the Soret band region, resulting in two asymmetrical bisignate Cotton effects. The (R)-guest molecule results in negative and positive first and second Cotton effects, while opposite signs are observed for the (S)-guests and a mirrorimage CD spectrum was obtained (Figure 49). Low temperatures and nonpolar solvents favor the induced chirality process, which is not surprising, given nonpolar solvents are known to stabilize the electrostatic interactions and low temperature to enhance host−guest interactions. Simultaneously, these researchers studied the chirogenic properties of the bis-chlorin analogue 27 with an ethane bridge (Figure 50).169 The chlorin-based host 27 is intrinsically optically active and has four stereogenic centers. Surprisingly, when chiral HPLC separations were carried out only the R,R/R,R and S,S/S,S enantiomers could be obtained with enantiomeric excesses of up to 88%. Contrary to what is observed with Bis-P systems,

Soret (B) band of the P ring contains well-resolved bands at 436, 419, and 410 nm. The centers of the MCD bands are very closely aligned with those on the absorption spectrum, which is consistent with nondegenerate excited states. It is important to note that transitions with differing polarizations generally have MCD bands of opposing sign. The two higher energy bands at 410 and 419 nm are positively signed in the CD spectrum but are found to have differing polarizations, since the higher energy MCD band at 408 nm was positively signed, while the lower energy MCD band at 424 nm was negatively signed. In TDDFT calculations, minus-to-plus CD patterns were predicted for the B// − B// and B⊥− B⊥couplings, resulting in a negatively signed band at lower energy with strong intensity and two partially resolved bands at higher energy (Figure 47). There is close agreement with the trends that were observed in the experimental spectra. Recently, Inoue et al. also reported a new application for bis(H2P) (26) as a chiral probe for several acids with enantiopure structures via a protonation mechanism (Figure 48)171 rather 6205


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Figure 57. Molecular structures of diphenyl ether-linked achiral Bis-P 33 and its chiral guests.

since the intensity is proportional to the square of the Q x transition moment value. In addition, the lower energies of the Q y and Bx bands, when compared to the Q x and By bands, enabled their opposing chirality signs to be assigned to differing clockwise and counterclockwise alignments of the coupled transitions with x and y polarizations, respectively. The calculation successfully reproduced the relative intensities and energy levels of the coupled transitions, in a manner that is particularly noteworthy where the three degenerate Q y-Q y, Q x-Q x, and Bx-Bx couplings are concerned. There was an overestimation of the CD intensity associated with the By-By coupling, however, since the observed CD intensity for the By band was expected to be less intense due to the smaller exciton splitting that is involved relative to the Bx band. It is noteworthy that this analysis predicts negative chirality for the most energetically isolated and red-shifted Q y transitions for the (R,R/R,R)-structure and provides unambiguous support for the absolute configuration that was assigned. The chirality induction and chiral recognition of the bischlorin supramolecular interactions with chiral guests was also investigated. The CD signals of the enantiopure bis-chlorin compound decreased due to the changes in conformation that were induced in the bis-chlorin rings. In addition, there were significantly different chiroptical responses for the corresponding antipodal guests.168,170 The distinctive chiral properties, therefore, facilitate the use of bis-chlorin compounds for the recognition of chirality. This chiral recognition involves a new model for enantioselective two-point host−guest interactions combined with the coupled dipoles of the host bischlorin, the alignments of which are completely controlled by the stereochemistry of the guest. Notably, the chiral recognition properties can be controlled by varying the bulkiness at the stereogenic center, resulting in a switch in the enantioselectivity.170

the strong optical activity was observed for both the Q and B bands in the mirror image CD spectra (Figure 51). In addition, the anisotropy factor calculated for the B band is 3 times lower than for the Q-band. It is also noteworthy that the Q and B bands had opposing signs in the CD spectrum, which provides information that the two transitions have distinct orientations with respect to the coupling transitions, apparently due to differing polarizations along the x and y axes of the chlorin. When the absolute configurations of the enantiomers are assigned, the coupling alignment for the lowest energy Q y band of the chlorin is particularly important due to its well-distinguished absorption properties. On this basis, the negatively signed Q y couplet for (R,R/R,R)-27 indicated a counterclockwise alignment of the transition moments, while for (S,S/S,S)-27, there is a positively signed couplet and a clockwise alignment. X-ray crystallography data for these bis-chlorins possess C2 symmetry with a V-type structure being formed, with reduced pyrrole rings in both chlorin rings being arranged in the closest possible spatial arrangement. When this geometry is considered, the Q y bands for the (S,S/S,S)-enantiomer create a clockwise twist, resulting in positive chirality when exciton coupling theory is applied. The direction of the coupling is the opposite of this for the (R,R/R,R)enantiomer, resulting in a negative chirality sign as can be seen in Figure 51. The TDDFT CD spectrum for the (R,R/R,R)-enantiomer was calculated to provide further evidence for this assignment, and close agreement is observed between the calculated and experimental spectra (Figure 52). The intensity of the out-ofphase Q y(−) band is predicted to be lower than the in-phase Q y(+) band, since it is partially forbidden, due to the V-shaped alignment of the coupled dipoles. The negligible CD intensity associated with Q x-Q x coupling was also correctly predicted, 6206


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Figure 58. CD and UV−visible spectra (in CHCl3 at 295 K) for 33: in the absence (CD silent) and presence (CD active) of (A) (R)-DAP, (B) (S,S)-DACH, (C) (S)-PPDA, (D) (S)-PEDA, and (E) (R,R)-DPEA at their maximum concentrations. Reprinted from ref 180. Copyright 2013 American Chemical Society.

4.2.2. Bis-Porphyrins Linked by Ether Chains. Bis-Ps linked by ether chains are good examples of the induction of chirality, since they can act not only as binding sites for the ditopic chiral guest molecules but also provide the reporters of the chiral sensors, and they can be used to recognize biologically important substrates and alkali ions. Bis-Ps can be linked using a single ether chain bridge. As a result, there is less rigidity in the system overall, so several conformations can coexist. For chirality to be successfully generated, the inductor of the asymmetry must stabilize the organization of assembly in spatial terms. The connected rare earth bis-Ps 28 and 29 (Figure 53) displayed intense CD signals in the Soret band region due to noncovalent interactions with the optically active guest molecules.175 The binding mode and the size of the guest molecule greatly affect the chiroptical signal. In addition, cysteine could be extracted with greater efficiency from aqueous solutions than other tested guest compounds when using the Yb complex of 28, as can be clearly concluded from the CD intensity of the corresponding 1:1 complex. When the longer homocysteine molecule is considered, Bis-P 29, which has a longer spacer, was more effective. Monti and co-workers reported Bis-P 30 with a polyethylene glycol linkage, which resulted in a less flexible bridge following the specific complexation of alkali metal ions (Figure 54).176 Upon addition of Na+, the chiroptical properties for the 1:1

tweezer compound that is formed by DACH and the Bis-P were effectively modulated; the CD signals at 436 nm were −620 and −415 cm−1•M−1 in the presence and absence of the Na+ ion, respectively. In addition, the association constants were modified in a similar manner, with an increase from 2.6 × 105 to 4.5 × 105 M−1. Interaction with chiral diamines results in supramolecular chiral complex formation featuring increased ellipticity and stability in the presence of Na+. This system should have promising applications in the construction of receptors and sensors for substrates. Similarly, in the presence of alkali ions, the binding affinities and the intensities of the CD bands were enhanced greatly for Bis-P 31 due to the interaction with the N-alkyl-substituted DACH (Figure 55).177,178 It was found that the K+-induced optical activity depended on the guest molecule. Guest compounds with alkyl groups that were sterically hindered prevent ditopic interactions that involve the Zn(II)Pc and terminal amino nitrogens, and no CD signals were detected. In contrast, significant but weak CD intensity was observed in the presence of K+. In addition, the Bis-P could be used to extract and probe the chiral properties of K+ salts because of the polyethylene glycol moiety and the K+-induced conformation with a tweezer-like structure. Kubo and co-workers reported Bis-P 32 that contains 1,1′-biphenyl crown-strapped bridging moieties (Figure 56).179 The induced CD signals resulting from interaction of the Bis-P 6207


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Figure 61. Molecular structure of the ether-linked chiral Bis-Ps 35 and 36.

Figure 59. Molecular structure of 34 using xylylene linkages.

Figure 62. CD spectra of the enantiomers of (a) 35 and (b) 36 in toluene at 20 °C. Reprinted from ref 184. Copyright 2006 American Chemical Society.

Figure 60. (a) Changes in the CD spectra for 34 (3.9 × 10−6 M) upon titration with (S)-mandelic acid [(S)-MA] in 1,2-dichloroethane (DCE) at 23 °C. The blue and red curves are spectra for [(S)-MA]/[34] concentration ratio ranges from 0−2 and 2−7, respectively. Plots of Δεmaximum − Δεminimum for the CD bands of (b) 34 (3.9 × 10−6 M) and (c) the relevant monomer (3.8 × 10−6 M) in the Soret region for the same [(S)-MA]/[34] ratios in DCE at 23 °C. Reprinted with permission from ref 183. Copyright 2003 Royal Society of Chemistry.

and chiral diamines was decreased upon the addition of Ba2+, indicating dissociation of the complex. This behavior is associated with the distance of the P units and disruption of the binding geometry due to extension of the strapped crown upon addition of Ba2+. Interestingly, no induced chirality was observed in the presence of Ba2+ for the interaction of the Bis-P

Figure 63. Molecular structure of ether-linked chiral Bis-P 37.

and a nonchiral diamine; however, if the same achiral diamine is added to a Ba2+-free solution of the system, it also resulted in a silent CD signal. This result indicated that Ba2+ served as a chiral conformation stabilizer in this system. It should also be noted 6208


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diphenyl ether bridge, has bisignate-induced CD signals in the Soret band region (Figures 57 and 58).180 The corresponding chiroptical properties depended on substituent size on the optically active guest molecule and the binding constant. Typically, the presence of bulky substituents on the chiral guest molecules prevents the guest ligand from binding with the host. In addition, the notably high amplitudes for the bisignate CD signals were due to high binding constants and the formation of unidirectional screws, while relatively less intense CD signals were ascribed to complexes with reduced stability. In contrast, the induced CD intensity was very weak when DPEA was present, since a counterclockwise twist of the two P units was formed with the large phenyl ring syn to the P ligand and this results in a negative first Cotton effect in the exciton couplet. When the large phenyl ring is anti to the P ligand, steric hindrance forced the two P moieties to form a clockwise twist alignment, this results in a positive first Cotton effect. The resulting positive CD signal for (R)-G3·33 is relatively weak, and this was attributed to the contribution of the counterclockwise twisted system being smaller than that of the orientation with a clockwise twist (Figure 58). Aida and co-workers introduced the first example of a chiralrecognition molecular probe with a D2 symmetry, fully substituted P ligand.181,182 Even though the enantiomers of the

Figure 64. Schematic representation of the enantioselective extraction of chiral C76 fullerene using chiral P host 37. Reprinted with permission from ref 80. Copyright 2014 Royal Society of Chemistry.

that the chiral memory of 32 was comparatively stable. The CD intensity is only slightly lower after 24 h. Recently, Rath and co-workers reported that in the presence of chiral diamines, the CD spectrum of Bis-P 33, which has a

Figure 65. Molecular structures of aromatic-ring-linked chiral Bis-Ps 38−42. 6209


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Figure 68. CD spectra of D2O/SDBS solutions of SWNTs extracted using (R)-40 and (S)-40. The concentrations of SWNTs in the solutions were normalized by their absorption peaks at 1024.5 nm. Reprinted from ref 188. Copyright 2008 American Chemical Society.

P monomer were barely separable due to thermal inversion, the monomer exhibited a distinct CD signal near the Soret band after it had interacted with an optically active carboxylic acid [for example, mandelic acid (MA)]. Notably, the molecule remained optically active even after the guest had been released. Thus, the relevant monomer memorized the chiral acid configurations. The researchers then synthesized Bis-P 34 with a chiral saddle-shaped structure using a xylylene linkage (Figure 59).183 This Bis-P exhibited a remarkable amplification of the corresponding monomer CD activity (greater than a factor of 7) for complexation with MA, since the nonplanar chiral properties are transferred from the P chromophore to the chiral helix of the supramolecular assembly (Figure 60). The absolute configurations of two saddled P rings in 34 with [(S)-MA]/ [34] = 2 were identical to one another, most likely due to monohydrogen-bonding with the (S)-MA. As a result, 34 adopts either a clockwise or counterclockwise helical twisting. For [(S)-MA]/[ 34] molar ratios exceeding two, third and fourth molecules of MA interact with inner binding sites, and this requires a significant expansion of the inner cavity of the macrocycle host. Such an expansion hinders the formation of helical conformations, leading to a decrease in the CD intensity of the supramolecular complexes. One of the intriguing examples of the type of optical activity that chiral porphyrinoids introduce is a series of heterocyclic Bis-P containing asymmetrically distorted N-alkylporphyrins (Figure 61).184,185 In this context, the optical activity resulted from the alkylation of a pyrrole nitrogen, leading to an asymmetric N-alkylporphyrin. The rigid structure prevents inversion of the structure. These N-alkylporphyrins are nonplanar because they cannot sterically accommodate the N-alkyl groups in their nitrogen cores. Therefore, their enantiomers were separated, and CD spectra with mirror symmetry were observed with split Cotton effects in the Soret band region (Figure 62). The chiral sensing properties of these hosts after noncovalent interaction with suitable guest molecules was explored. The cavity between the P rings of Bis-P 37 was used to accommodate spheroidal fullerenes such as C76. For example, the chiral properties of 37 were used to discriminate the enantiomers of C76 and for enantioselective extraction, leading to a 7% enantiomeric excess in a single procedure, because chiral P dimer has a high π-basicity and a large asymmetric distortion (Figures 63 and 64).185

Figure 66. CD and absorption spectra of Bis-P (R)- and (S)-38 (nubmering 1 in figure) and their complexes with SWNTs (NTs· (R)−38 and NTs·(S)−38) in methanol. (a) 380−500 nm and (b) 500− 700 nm. The concentrations of the Bis-Ps and SWNTs·(R)−38 and SWNTs·(S)−38 were the same in the (R)- and (S)-38 solutions as confirmed by the intensities of the Soret band absorptions. Reprinted from ref 186. Copyright 2007 American Chemical Society.

Figure 67. CD spectra of D2O/SDBS solutions of SWNTs extracted using 39 and 38. The SWNTs were recovered from the supernatant after centrifugation for 5 h and washed with pyridine several times to remove chiral Bis-Ps completely. The concentrations of SWNTs in these solutions were normalized by their absorption peaks at 980 nm. Reprinted from ref 187. Copyright 2007 American Chemical Society. 6210


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Figure 69. Computer-generated complex structures for (R)- and (S)-41 (nubmering 1 in figure) with (P)- and (M)-(6,5)-SWNTs. Reprinted from ref 189. Copyright 2010 American Chemical Society.

4.2.3. Bis-Porphyrins Linked by Aromatic-Ring-Related Units. Komatsu and co-workers reported a series of chiral nanotweezers comprising aromatic-bridged zinc(II) Bis-Ps 38−42 (Figure 65).186−190 There are four stereogenic centers due to modification of the structure at two positions on both P chromophores. The chiral structure is predetermined as exclusively R or S, because enantiopure phenylalanine was used during the synthesis. Two P rings were connected in a rigid manner with a series of aromatic bridges, leading to differing spatial macrocycle alignments. For example, (R)-38 and (S)-38 displayed mirror image bisignate Cotton effects at split Soret absorption bands (Figure 66a).186 After extraction of the SWNTs with (S)- or (R)-38, red-shifted bands were observed at 415 and 430 nm in the Soret band region, along with a new broad band at ca. 450 nm. Substantial intensification of red-shifted symmetrical CD bands were also observed at 448 and 433 nm (Figure 66a). Electronic interactions between the Bis-Ps and the SWNTs upon complex formation causes the red shift of the spectral bands. Since supramolecular chirality results from noncovalent interaction with carbon nanotubes, these Bis-Ps can discriminate SWNTs based on their diameter and helicity, which is related to the shape and size of the cleft formed by the two P rings and their linking spacers. The enhanced CD signals are probably related to the fixed conformer arrangement of the two P planes after complex formation. The CD bands were observed in the characteristic Q-band region for Ps between 500−700 nm at 562 and 596 nm (Figure 66b). Symmetrical absorption bands were observed for the ES SWNTs at 1002 and 986 nm, in the spectra of the SWNTs·(S)-38 and SWNTs·(R)-38 complexes. Once the chiral nanotweezers are removed, the Bis-P-free SWNTs that are formed had symmetric CD bands with opposite signs. This indicates that Bis-Ps were liberated to provide optically enriched SWNTs. The authors then developed a new chiral nanotweezer using 2,6-pyridylene-bridged Bis-P 39 with improved SWNT extraction ability.187 The most likely explanation is that the dihedral angle formed by the two P rings of 93.8° is smaller than that of 111.2° for 38. This subtle structural change in the nanotweezer molecule was found to lead to significant improvement in its ability to extract and chirally discriminate SWNTs. After the chiral nanotweezers have been thoroughly removed, the CD spectra of SWNT solutions that were extracted using

Figure 70. Molecular structure of aromatic-ring-linked chiral Bis-P 43.

(S)- and (R)-Bis-Ps had symmetrical bands as can be observed in Figure 67. Two intense bands that lie at 341 and 562 nm in the CD spectra of SWNTs extracted using 39, arise, respectively, from the ES33 and ES22 transitions of (6,5)-SWNTs.191 The presence of these spectral bands demonstrates that 39 has a much greater ability to discriminate the helicities of (6,5)-SWNTs. A 3,6-carbazolylene-bridged Bis-P 40 was also synthesized by the same research group.188 Extraction using 40 results in a significant optical enrichment of (7,5)-SWNTs, along with simultaneous enrichment of (7,5)- and (8,4)-SWNTs. The extracted fraction displays mirror-imaged CD spectra, which indicates that the R and S stereoisomers of 40 preferentially extract SWNTs with differing M and P helicities, respectively, and that optically active SWNTs are extracted. The intense CD bands at 639 and 374 nm can be assigned, respectively, to the ES22 and ES33 transitions of (7,5)-SWNTs (Figure 68). This demonstrates that 40 discriminates the helicity of (7,5)-SWNTs to yield optically enriched extracts, while other (n,m)-SWNTs could not be optically enriched in this manner. In a similar manner, extraction with 39 results in the preferential extraction of optically enriched (6,5)-SWNTs. Although the (7,5)- and (6,5)-SWNT structures do not differ significantly in their roll-up angles (ca. 2.5°) and 6211


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the right- and left-handed structures of the (6,5)-SWNTs were selectively discriminated, with ee values for the extracted SWNTs reaching as high as 67% (Figure 69). Subsequently, a new Bis-P (so-called nanocalipers) 42 with a much longer spacer was designed by the same research group.190 The two chiral P units are aligned in a parallel manner by the spacer, which consists of carbazole−anthracene−carbazole aromatic groups and has a length greater than 1.4 nm. The significantly larger and deeper cavity of this system can accommodate SWNTs with diameters that are larger than 1.0 nm. Optically active SWNTs with large diameters were accumulated after extraction using the chiral system. It was found that the nanocalipers also recognize SWNT metallicity, and this leads to the enrichment during extraction of metallic SWNTs. The chiral nanocalipers exhibit multifunctional capabilities, therefore, for the recognition of the physical and structural properties of SWNTs, such as diameter, metallicity, and helicity. A novel system 43 with 2,2′-biphenol-bridged Ps can be used to determine the absolute configuration of monoamine structures through hydrogen-bonding interactions with the biphenol groups (Figure 70).193 2,2-Biphenols have intrinsic chirality and exist as two conformers, M and P, with structures differing only in rotation around a single bond at the center of the structure. At room temperature, unsubstituted structures interconvert rapidly and equilibrating M and P conformers are present in a 1:1 mixture. Rotation is hindered when substituents are placed on the ring or the equilibrium can be disturbed through interactions with a chiral group external to the structure, and this causes one conformer to be favored energetically, resulting in observable Cotton effects in the CD spectra. Bis-P 43 displays intense exciton coupling corresponding to the Soret absorption band of Ps following the introduction of certain alkyl and aryl chiral amines, while specific helicities for the biphenol group predominate when chiral amines are complxed. Specifically, (R)-amines were observed to induce a positive Cotton effect, while a negative Cotton effect was observed for (S)-amines (Figure 71). The authors speculated that steric hindrance played a key role in the induced configuration. For M-(S) diastereomer A, the medium-sized CH3 group lies in a less sterically hindered area, while the smallest H group lies in the most sterically crowded region. In contrast in the P-(S) diastereomer, the cyclohexyl moiety was located at the location that is least sterically demanding, and steric hindrance occurs between

diameters (ca. 0.07 nm), the differing optical enrichments occur when the spacer is changed from pyridylene to carbazolylene. This demonstrates that Bis-Ps can be used to discriminate subtle structural differences in SWNT structures and provides additional support for the earlier finding that relatively minor changes in the Bis-P structure determine which SWNTs will be preferentially extracted. Bis-P 41 has phenanthrene bridging units and shows high selectivity for (6,5)-SWNTs with very small diameters from a solution containing CoMoCAT-SWNTs as the major components. The SWNTs were prepared by using chemical vapor deposition (CVD) with a Co−Mo catalyst on a silica-support.192 The high selectivity was attributed to the presence of a cleft between the two Ps that is relatively narrow.189 In addition,

Figure 71. Proposed working model for assigning the absolute stereochemistry of chiral amines. Complexation of (S)-cyclohexyl ethyl amine with 43 is illustrated for host molecules with both M and P helicity. The P-(S) complex leads to positioning of the medium CH3 group in a sterically encumbered region compared to that in the M-(S) complex, which places the smallest group (H) in the same comparable location. The experimental results yielded a strong negative ECCD spectrum that corroborated the predicted assignment. Reprinted from ref 193. Copyright 2014 American Chemical Society.

Figure 72. Molecular structures of aromatic-ring-linked chiral Bis-P 44 and guest molecules G12−14. 6212


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Mg(II) centers therefore adopt a square pyramidal five-coordinate geometry, and large changes in the conformational structure of (G13)2·44 occur (Figure 73). The chiral information transfer from an enantiopure ligand to a nonchiral host was expected for the unidirectional twist structure adopted by the Bis-P rings.

the medium-sized CH3 group and the substituents on the P ring. Therefore, the axial chirality depended on the steric repulsion between the bulky substituents on P rings and the guest molecules. The stoichiometry of the guest and host molecules often plays an important role during the formation of different association species in supramolecular systems, particularly in systems that contain more than one binding site. Rath and co-workers investigated how stoichiometry affects the induced chirality process of supramolecular complexes with 44 as the host molecule for vicinal diol chiral guest molecules (Figure 72).194 It can be observed in the X-ray crystal structure that G13 coordinates the Mg(II) center in an endo−endo manner, since interligand H-bonding of the OH groups is stabilized. The two

Figure 75. Selected spectra of the UV−visible (top) and CD titrations (bottom) of 45 (left) and 46 (right) with (R,R)-DACH showing the Soret band region. Number of equivalents added: 0, 1, 2, 10, 50, or 100. Reprinted with permission from ref 196. Copyright 2008 Royal Society of Chemistry.

Scheme 2. Complexation Equilibria Involved in the Coordination of Diamine (R,R)-DACH to Bis-Ps 45−46 and a Schematic Representation of the Species Involveda

Figure 73. Perspective view of (G13)2·44 showing 50% thermal contours for all of the nonhydrogen atoms at 100 K (H atoms have been omitted for clarity). Reprinted with permission from ref 194. Copyright 2014 Royal Society of Chemistry.

a

The overall K21 and stepwise binding constants K11 and K11↔21, as well as their relationships with Km (microscopic binding constant) and EM (effective molarity) are also indicated. Reprinted with permission from ref 196. Copyright 2008 Royal Society of Chemistry.

Figure 74. Molecular structures of achiral chain-linked Bis-Ps 45 and 46. 6213


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Figure 76. Molecular structure of achiral chain-linked Bis-P 47.

Figure 79. Molecular structure of achiral chain-linked Bis-P 49.

Figure 77. CD spectra of the Bis-Ps ZnII47 and RhIII47 following coordination with (R,R)-DACH to form 1:1 complexes. Reprinted from ref 197. Copyright 2012 American Chemical Society.

Figure 78. Molecular structures of achiral chain-linked Bis-Ps 48a−48c.

Figure 80. Proposed mechanism for the CD enhancement of 49 via the binding of guest molecules. Reprinted with permission from ref 200. Copyright 2012 Wiley-VCH.

4.2.4. Bis-Porphyrins Linked by Other Achiral Chains. Similar to Bis-Ps linked by ethane and ether units, other linking moieties have been used to generate supramolecular chiral structures. Since both the P and the linking moieties are not

chiral, chiral guest molecules are required to induce asymmetry in these systems. The supramolecular structures can be used for 6214


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Figure 81. Molecular structures of achiral ferrocene-linked Bis-P 50 and chiral diamine guests.

Figure 83. Molecular structure of m-phthalic diamide-linked Bis-P 51.

Figure 82. CD spectra of 50 in the absence and presence of chiral diamine guests in dichloromethane solution (1 × 10−6 M) at 295 K. Reprinted from ref 201. Copyright 2014 American Chemical Society.

Figure 84. Space-filling representation of the helical chain with P configuration of 51 formed by Zn−O coordination bonds along the c axis. Reprinted from ref 202. Copyright 2014 American Chemical Society.

chiral sensing and to determine the absolute configuration of the guest molecules. Ballester and co-workers described the chiroptical properties of Bis-Ps constructed using flexible 1,3-dicarbonylaryl groups as bridges with enantiopure (R,R)-DACH (Figure 74).195,196 Interestingly, chirality inversion of the system was stoichiometrically controlled upon interaction with enantiopure (R,R)-DACH. The Bis-Ps 45 and 46 formed 1:1 sandwich complexes at low (R,R)-DACH concentrations. Upon complex formation, bisignate

negative Cotton effects are observed at the Soret band end of the porphyrin spectrum. Increasing the concentration of the guest induced the destruction of the initially formed 1:1 sandwich complexes, ultimately yielding open 2:1 complexes, which exhibited a weak, positive CD couplet in the Bis-P Soret bands when the enantiopure diamine is present in significant excess. This result was explained by the opposite orientations of the 6215


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Figure 85. CD spectra of crystallites of 51 in KBr pellets. The two pellets were prepared using selected crystals. Reprinted from ref 202. Copyright 2014 American Chemical Society. Figure 87. Molecular structures (at 100 K) of the (A) molecule I (counterclockwise) and (B) molecule II (clockwise) components of [(S)-G3]3·[52]2 (H atoms and ethyl groups have been omitted for clarity). Reprinted with permission from ref 204. Copyright 2015 Royal Society of Chemistry.

Figure 86. Molecular structure of pyrrole-linked Bis-P 52.

coupled electronic transitions of the 1:1 and 2:1 complexes, (R,R)-DACH·45 and [(R,R)-DACH]2·45 (Figure 75, Scheme 2). In brief, the self-assembly process between 45 or 46 and (R,R)-DACH produced a supramolecular chirality induction phenomenon, and the sign of the couplet was determined by the stoichiometries of the complexes. Subsequently, the same group further explored the influence of the solvent and metal center through a comparative study of the coordination of (R,R)-DACH with ZnII47 and RhIII47 (Figure 76).197 A 1:1 sandwich-like complex was formed for both P tweezer receptors upon initial addition of the chiral diamine. The 1:1 complex was then converted to the open 2:1 complex when the diamine guest was present in excess. As expected, the 1:1 and 2:1 complexes of the Bis-P RhIII47 were more stable thermodynamically than those of the Bis-P ZnII47. In a toluene solution, the Bis-P ZnII47 experienced a chirality transfer process, with the inversion of chirality controlled by the complex stoichiometry (there are opposite couplet sign sequence for the 1:1 and 2:1 complexes). However, the Bis-P RhIII47 afforded 1:1 and 1:2 complexes which exhibited the same sign for their CD

Figure 88. (a) Structure of Bis-P 53. (b) Binding of a chiral diamine to 53 leads to a helical disposition of the P rings dictated by the sterics at the chiral center. The resultant ECCD is used to assign the absolute stereochemistry of the chiral center. Reprinted from ref 205. Copyright 2001 American Chemical Society.

couplets and did not undergo inversion of chirality. In dichloromethane, only ZnII47 yielded 1:1 and 1:2 complexes that are CD-active, while in contrast, the RhIII47 has a 1:2 complex that is CD-silent. Moreover, the sign of the bisignate CD couplet of the 1:1 rhodium complex, (R,R)-DACH·RhIII47, was opposite to that obtained using the Zn(II) analog, ZnII47, in both solvents (Figure 77). These observations are most likely due to the higher thermodynamic and kinetic stability of the RhIII−N coordination bond in the coordination complexes. Additionally, this study revealed that the effective molarity values (EM) determined for the 1:1 sandwich complexes were strongly 6216


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Scheme 3. Synthetic Procedure and Chemical Structure of Metal-Coordinated Bis-P 54

Figure 89. CD and UV−vis spectra of 54 upon addition of 3Cu(ClO4)2 + 3NH4NCS in methylene chloride and

Optically Active Porphyrin and Phthalocyanine Systems - Chemical

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