Chiroptical Transcription of Helical Information through Supramolecular Harmonization with Dynamic Helices

Article abstract of DOI:10.1021/ja039369p

With biologically important "peptide bundling" as the motif, new chromophoric cyclic host 1 was designed, which consists of two zinc porphyrin units that are connected by dynamic peptide helices of nonameric aminoisobutyric acid (Aib) units. Upon inclusio

Full text of DOI:10.1021/ja039369p

Published on Web 12/31/2003
Chiroptical Transcription of Helical Information through Supramolecular
Harmonization with Dynamic Helices
Yan-Ming Guo,† Hideaki Oike,*,† and Takuzo Aida*,†,‡
Aida Nanospace Project, Exploratory Research for AdVanced Technology (ERATO), Japan Science and Technology
Agency (JST), 2-41 Aomi, Koto-ku, Tokyo 135-0064, Japan, and Department of Chemistry and Biotechnology,
School of Engineering, The UniVersity of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Received November 1, 2003; E-mail: oike@nanospace.miraikan.jst.go.jp; aida@macro.t.u-tokyo.ac.jp
Helices are indispensable structural elements in biological
systems, and molecular design to sense helical structures is an
interesting subject for better understanding of the stereochemical
aspects of biological events.1 Transcription of helical information
may also be an important step to realize molecular informatics with
biological macromolecules. Here we report a novel bioinspired
approach to the transcription of helical information, using “bundling
of peptide helices” as a motif for molecular design. Thus, we
synthesized a chromophoric cyclic host (1, Chart 1; see also Figure
1a) consisting of two zinc porphyrin units that are connected by
oligo(aminoisobutyric acid) (Aib) posts.2 Although poly(Aib) is
Figure 1. Molecular models of (a) 1 and (b) inclusion complex of 1 with
L-2. The structures were created by combining a MM2-optimized structure
devoid of any chiral centers, it adopts a helical conformation due
to a steric requirement of the C(CH3)2 unit.3 It is also noted that
the helical chain of poly(Aib) is dynamic, i.e., an equilibrium
mixture of thermodynamically interconverting right- and left-handed
helices.3-5 We found that 1 can develop intense chiroptical signals
upon inclusion of helical guests via stereochemical harmonization
with the dynamic helical chains used for the post component.
Cyclic host 1 was obtained by metalation with Zn(OAc)2 of a
precursor free-base porphyrin, synthesized by coupling of an Aib
nonamer with 5,15-bis(3-aminophenyl)-10,20-dimesitylporphyrin,
followed by macrocyclization with 5,15-bis(3-carboxyphenyl)-
10,20-dimesitylporphyrin.6 On the basis of spectroscopic titration
and Job’s plots,6 host 1 in CHCl3 was found to form a stable 1:1
inclusion complex with guest molecule L-2 (Figure 1b), a pyridine-
anchored helical guest containing a (L)-leucine residue at its center
(Chart 1). The association constant Kassoc was evaluated to be 1.7
× 106 M-1. Although 1 is CD-silent, inclusion complex 1⊃L-2
displayed an intense exciton-coupled CD signal at the Soret
absorption band of the zinc porphyrin moieties (410-450 nm)
(Figure 2a, red solid curve), while 1⊃D-2 showed a mirror-image
CD spectrum (red broken curve) of 1⊃L-2. The inclusion complexes
also showed CD bands in a short wavelength region, which most
likely originate from the meso-aryl groups of the zinc porphyrin
units, since the guest molecules themselves exhibit only negligibly
weak CD bands at 250-350 nm.6 These observations suggest that
the two zinc porphyrin units of 1, upon inclusion with helical 2,
adopt a twisted geometry in either clockwise or anticlockwise
manner, depending on the helical sense of the guest.2b In sharp
contrast, when a nonhelical guest such as L-3 was used for the
complexation with 1, a CD-silent inclusion complex with a much
smaller association constant (Kassoc ) 0.04 × 106 M-1) resulted.6
Host 1 remained CD-silent even upon addition of a large excess of
L-3 (e.g., 60-fold) with respect to 1. Likewise, helical guest L-2
(mono) carrying only a single pyridyl terminal (Chart 1) showed a
poor binding affinity and did not gave a CD-active complex.6
Therefore, it is most likely that inclusion of the guest with a helical
of the zinc porphyrin unit and a crystallographically defined 310-helical
structure of oligo(Aib).3
Chart 1. Schematic Structures of Hosts 1 and Guests 2 and 3
conformation plays an essential role in generating a twisted
geometry of the two facing zinc porphyrin units.
We also synthesized host molecule 1∆Phe having, at the post parts,
chromophoric dehydrophenylalanine (∆Phe) units, since ∆Phe-
containing single-handed peptides display enhanced CD bands
centered at 280 nm, whose signs have been correlated with the
helical senses.4 Similar to the case with 1, new host 1∆Phe was found
to form CD-active inclusion complexes with helical guest 2
(1∆Phe⊃2; Kassoc ) 1.5 × 106 M-1).6 As shown in Figure 2a (blue
curves), the exciton-coupled CD signals at the Soret absorption band
of 1∆Phe⊃2 are less intensified than those observed for 1⊃2. On
the other hand, the CD spectral pattern in the short wavelength
region is different from that of 1⊃2, because of a possible overlap
† ERATO Aida Nanospace Project, JST.
‡ The University of Tokyo.
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C O M M U N I C A T I O N S
Figure 2. (a) CD spectra of 1 (red) and 1∆Phe (blue) in the presence of L-2
(solid curves) and D-2 (broken curves) ([guest]/[host] ) 1.0) in CHCl3 at
25 °C. (b) Differential spectra by subtraction of the CD spectrum of 1⊃L-2
from that of 1∆Phe⊃L-2 (solid curve), and subtraction of the CD spectrum
of 1⊃D-2 from that of 1∆Phe⊃D-2 (broken curve).
Figure 3. (a) CD spectra of 1 (red) and 1∆Phe (blue) in the presence of
L-2∆Phe (solid curves) and D-2∆Phe (broken curves) ([guest]/[host] ) 1.0)
in CHCl3 at 25 °C. (b) Differential spectra by subtraction of the CD spectrum
of 1⊃L-2∆Phe from that of 1∆Phe⊃L-2∆Phe (solid curve), and subtraction of
the CD spectrum of 1⊃D-2∆Phe from that of 1∆Phe⊃D-2∆Phe (broken curve).
porphyrin chromophores. Stereochemical selection of helices
through elaboration of the host structures is one of the subjects
worthy of further investigation.
of the CD band originating from the meso-aryl groups of the zinc
porphyrin units with that of the ∆Phe-containing oligopeptides
posts. In fact, when the CD spectra of 1⊃2 (red curves) were
subtracted from those of 1∆Phe⊃2 (blue curves) in Figure 2a, in a
way that the CD signals at the Soret band region were canceled,
green curves in Figure 2b were obtained as differential spectra,
which are virtually identical to the CD spectral profiles of ∆Phe-
containing single-handed oligopeptides.4 This observation gave an
insight that the dynamic helices in the post parts of 1, upon inclusion
of L-2 and D-2, adopt, as judged from the CD signs,4 right- and
left-handed helical conformations (solid and broken curves in Figure
2b), respectively.
Acknowledgment. We thank N. Saeki and G. Ogawa for
experimental assistance.
Supporting Information Available: Details for synthesis and
characterization of 1, 1∆Phe, 2, 2∆Phe, 2 (mono), and 3, and results of
UV-vis and CD titration experiments and Job’s plots (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
References
Since the helical conformations of L-2 and D-2 are not
established, we utilized conformationally defined L-2∆Phe (right-
handed) and D-2∆Phe (left-handed) as the helical guests for the
inclusion with 1 and 1∆Phe (Chart 1).4,6 The Kassoc values of 1⊃2∆Phe
and 1∆Phe⊃2∆Phe were 2.1 × 106 and 2.3 × 106 M-1, respectively,6
which are close to those for the inclusion complexes with 2. On
the other hand, the CD spectra of 1⊃2∆Phe and 1∆Phe⊃2∆Phe (Figure
3a), though significantly enhanced in the short wavelength region
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sense helical conformations of oligopeptides. The results clearly
indicate that dynamic helical peptides are stereochemically har-
monized with right- or left-handed peptide helices in a confined
nanospace, leading to a chiroptical output from the connecting zinc
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