Articulated rods - A novel class of molecular rods based on oligospiroketals (OSK)

Article abstract of DOI:10.3762/bjoc.11.11

We developed a new type of molecular rods consisting of two (or more) rigid units linked by a flexible joint. Consequently we called these constructs articulated rods (ARs). The syntheses of ARs were carried out by a flexible and modular approach providing access to a number of compounds with various functionalizations in terminal positions. First applications were presented with pyrene, cinnamoyl and anthracenyl labelled ARs.

Full text of DOI:10.3762/bjoc.11.11

Articulated rods – a novel class of molecular rods
based on oligospiroketals (OSK)
Pablo Wessig*1, Roswitha Merkel1 and Peter Müller2
Full Research Paper
Open Access
Address:
Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24–25,
Beilstein J. Org. Chem. 2015, 11, 74–84.
1
doi:10.3762/bjoc.11.11
D-14476 Potsdam, Germany and 2Institut für Biologie/Molekulare
Biophysik, Humboldt Universität zu Berlin, Invalidenstr. 42, D-10115
Berlin, Germany
Received: 08 October 2014
Accepted: 08 January 2015
Published: 16 January 2015
Email:
Pablo Wessig* - wessig@uni-potsdam.de
Associate Editor: S. C. Zimmerman
*
Corresponding author
© 2015 Wessig et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
articulated rods; click chemistry; molecular rods; oligospiroketals;
pyrene excimer
Abstract
We developed a new type of molecular rods consisting of two (or more) rigid units linked by a flexible joint. Consequently we
called these constructs articulated rods (ARs). The syntheses of ARs were carried out by a flexible and modular approach providing
access to a number of compounds with various functionalizations in terminal positions. First applications were presented with
pyrene, cinnamoyl and anthracenyl labelled ARs.
Introduction
One of the basic principles in living nature is based on shape- decades [1-6]. Molecular rods, i.e., conformational rigid mole-
persistent and relatively rigid molecular and supramolecular cules in which the length considerably exceeds width and height
systems. These systems mainly consist of peptides and proteins (large aspect ratio), can roughly be divided into conjugated and
(
e.g., scleroproteins, globular proteins, and membrane proteins), non-conjugated rods. Whereas the former are of particular
lipids (e.g., biological membranes), carbohydrates (e.g., cellu- interest for nanoelectronics [7], the latter are regularly used in
lose) and nucleic acids (DNA, RNA). The impressive perfor- biological applications. Several years ago we developed a new
mance of the natural systems is achieved by an enormous effort, class of molecular rods whose structure is based on spirocycli-
as measured by the molecular weight of the biomolecules. cally joined saturated six-membered rings [8]. The key step of
Mimicking natural construction principles with artificial the synthesis of these rods is the formation of ketals and we
systems is one of the most challenging tasks of synthetic therefore name this class of compounds oligospiroketals
organic chemistry. In general, the components of these systems (OSKs).
are similar to mechanical parts: rods, joints, sleeves, plates etc.,
but with nanoscopic scale. Amongst these building blocks, Although the backbone of OSK rods contains many oxygen
molecular rods attracted particular attention in the last past atoms, these atoms are shielded by adjacent methylen groups
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Beilstein J. Org. Chem. 2015, 11, 74–84.
and, consequently, OSK rods are rather hydrophobic. Combined
with their rigidity this causes dramatically reduced solubility of
longer OSK rods (with more than 6–7 rings). This problem
could be circumvented by the introduction of solubility
enhancing groups (SEGs), either in terminal or lateral positions
of the rods. Building blocks with lateral SEGs are called
sleeves. In Figure 1 a typical sleeve D (cyan) as well as other
typical building blocks of OSK rods are depicted, such as
pentaerythritol C (red), cyclohexane-1,4-dione E (green), and
piperidine-4-ones B (blue). An OSK rod A composed of these
structural elements exhibits a length of ca. 3 nm [9]. Later, other
Figure 2: Fundamental structure of articulated rods (blue = legs,
red = joint, green = terminal functionalities).
sleeves were developed and a method for quantifying the iv) functionalizing the terminal positions of the ARs, and
rigidity of molecular rods was established [10]. v) (possibly) introduction of solubility enhancing groups.
Several applications of OSK rods were explored in the past Our strategy is summarized in Figure 3. We defined a 1,2,3-tria-
years. Worthy of note are the incorporation in biological and zole containing linkage between two piperidine rings as the
artificial membranes [11-13], the utilization as spacer in FRET flexible joint F, which should be easily accessible by copper-
systems [14], and as building blocks in porous materials [15].
Although stiffness of the whole rod is desirable in many cases, a
partial flexibility is often necessary. Especially for biological
and biochemical applications this facilitates perfect adjustment
between artificial and biological systems. This can be achieved
by constructs consisting of rigid legs connected by a flexible
joint. An outstanding feature of these systems is the equilib-
rium between a straight (STR) and a folded (FOL) con-
formation (Figure 2). Herein we wish to report on the synthesis
and properties of a new class of semi-flexible molecules which
we called articulated rods (ARs).
Results and Discussion
Synthesis of articulated rods (ARs)
The synthetic strategy towards ARs has to address the following
issues: i) synthesis of legs (short rods) with orthogonal
protecting groups at both ends, ii) selective deprotection/acti-
Figure 3: Synthetic strategy towards articulated rods.
vation of each of these groups, iii) construction of the joint,
Figure 1: Typical OSK rod A with solubility enhancing sleeve (D) and building blocks B,C,E.
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Beilstein J. Org. Chem. 2015, 11, 74–84.
catalyzed cycloaddition between an azide G and a terminal
alkyne H (CuAAC, “Click” reaction) [16]. Primary alcohols I
serve as “protected” azides accessible by modified Appel reac-
tion [17]. The alkynes H can be protected by silylation (J)
because only primary alkynes react in the CuAAC (Figure 3).
The synthesis commences with 4-hydroxypiperidine (1), which
was converted to piperidine-4-one 3 bearing a protected alkyne
moiety as well as to piperidin-4-one 5 with a PMB protected
hydroxy group, each in two steps. The trispirane 7 was prepared
in two steps from ketones 3 and 5 by an acetalization with
pentaerythritol under classic conditions followed by reaction of
the resulting diol 6 with 5 using our previously developed
method of double activation [8]. Finally, the PMB group was
cleaved by DDQ to give the orthogonally protected trispiro rod
8
(Scheme 1).
To demonstrate the capability of the approach outlined in
Figure 3 we selectively activated both sides of building block 8
either by introduction of an azide group (9) or liberation of the
terminal alkyne by desilylation (10). The subsequent CuAAC
coupling between 9 and 10 turned out to be difficult. Whereas
the reaction failed under standard conditions [18] we succeeded
after numerous variations of the reaction conditions by applying
the Cu/C catalyst [19] in a solvent mixture of DCM and MeOH
in the presence of Et3N (Scheme 2).
With the first articulated rod 11 in hands we investigated
whether it is possible to selectively activate the “click-function-
alities” again.
Scheme 1: Synthesis of building block 8 (i: trimethylsilylpropargyl-4-
nitrophenylcarbonate. ii: Dess–Martin-periodinane. iii: pentaerythritol,
pTsOH (cat.). iv: 2-(4-methoxybenzyloxy)acetic acid, DCC, HOBt.
v: (COCl)2/DMSO. vi: NaH, TMSCl, TMSOTf, vii DDQ, DCM, buffer
pH 7).
To our delight 11 could be converted in good yields both to the
unprotected alkyne 12 and to the azide 13. Coupling of these
articulated rods using the previously optimized CuAAC condi-
Scheme 2: Synthesis of articulated rod 11 (i: CBr4, PPh3, NaN3. ii: K2CO3/MeOH. iii: Cu/C DCM/MeOH 1:1, cat. Et3N).
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Beilstein J. Org. Chem. 2015, 11, 74–84.
tions afforded the triple articulated rod 14 in satisfactory yields Accordingly, articulated rod 25 was obtained in nine steps
(
Scheme 3). It should be noted that the molecule 14 already has (Scheme 4). To our delight, 25 could be successfully cyclized to
a length of nearly 7 nm in the stretched conformation. Further- 26 using the above mentioned CuBr/DBU catalyst albeit with
more, we activated both ends of 11 in two steps to give the AR moderate yield (Scheme 5).
1
5 and undertook several attempts to cyclize this compound
using the hitherto successful catalyst Cu/C. The cyclization of After having demonstrated that articulated rods can be irre-
articulated rods could be a promising approach to produce versibly fixed in the folded conformation we investigated the
bundles of rods with increased stiffness. Unfortunately, we equilibrium between the straight and the folded shape of the
obtained only insoluble solids, which could not be further char- articulated rods (cf. Figure 2). For this purpose we first chose
acterized. Only with CuBr in the presence of DBU [20] we pyrene moieties which are perfectly suited to detect this equilib-
received evidence for a cyclization of 15 from IR and MS rium owing to the distance dependent change in the fluores-
spectra.
cence spectrum. Furthermore, we were interested in functional
groups in the terminal positions of the ARs enabling reversible
At this point we could not rule out that polymerization of 15 switching between the two states. This was supposed to be
occurred instead of the desired cyclization. On the other hand it accomplished both by [2 + 2] photocycloaddition of derivatives
was obvious that the cyclization product can be insoluble due to of cinnamic acid and [4 + 4] photocycloaddition of anthracene
the dramatically reduced conformational flexibility.
derivatives. At first we pursued a sequential approach by intro-
ducing the pyrene-1-ylacetyl and the cinnamoyl moieties in a
To prove this hypothesis we developed a articulated rod bearing two-step sequence in 4-hydroxypiperidine with subsequent
solubility enhancing groups. Starting with PMB-protected and oxidation to give piperidin-4-ones 27a,b. An appropriate
enantiomerically pure 2-hydroxy-4-methylpentanoic acid 16, anthracene derivative was not accessible by this approach due
which is easily accessible from L-leucine [21] we pursued a to the high sensitivity of the anthracene moiety against various
similar strategy as described above for articulated rod 15. oxidation conditions. For the construction of articulated rods we
Scheme 3: Sequential deprotection of 11 and synthesis of triple articulated rod 14 (i: K2CO3/MeOH. ii: CBr4/PPh3/NaN3.iii: Cu/C, Et3N. iv: CBr4/PPh3/
NaN3.).
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Beilstein J. Org. Chem. 2015, 11, 74–84.
Scheme 4: Synthesis of articulated rods 23–25 with increased solubility (i: 4-hydroxypiperidine, DCC, HOBt. ii: (COCl)2/DMSO. iii: 6, NaH, TMSCl,
TMSOTf. iv: DDQ. v: K2CO3/MeOH. vi: CBr4/PPh3. vii: Cu/C, Et3N. viii: K2CO3/MeOH. ix: CBr4/PPh3/NaN3).
Scheme 5: Macrocyclization of articulated rod 25.
also prepared alkyne 28 by deprotection of diol 6. In addition
we used the literature known building blocks 27c (see below the
convergent approach) and 29 [9] (Scheme 6).
Scheme 6: Synthesis of building blocks 27–29 (i: 1. pyrene-1-ylacetic
acid, DCC/DMAP, 68%; 2. Dess–Martin periodinane 89%. ii: 1.
cinnamoyl chloride, iPr2NEt, 94%; 2. Dess–Martin periodinane, 86%.
iii: K2CO3/MeOH).
Based on ketones 27a–c and diols 28, 29 we obtained ARs
3
2a–c in two steps consisting of the established double acti-
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Beilstein J. Org. Chem. 2015, 11, 74–84.
vation acetalization [8] and the CuAAC, catalyzed by Cu/C, affords compounds 33a–c in moderate to good yields, whereas
with moderate yields (Scheme 7).
the reaction with NaN3 provided the ω,ω’-diazide 34. The latter
compound served as interface for labelling with various alkyne-
As mentioned above this sequential approach failed in the case functionalized compounds. As proof-of-concept we success-
of anthracene. In addition a convergent approach in which the fully coupled 34 with the perylene derivative 35 to give 36
terminal functionalities are introduced as late as possible in the (Scheme 8).
synthesis (ideally in the last step) would be an advantage.
Besides the widely used CuAAC ligation the Staudinger liga-
We achieved this goal starting with the ω,ω’-dielectrophilic AR tion [22] is also an important tool for coupling molecules. To
3
2c. Thus, treatment with different potassium carboxylates verify that the diazide 34 is also suitable for this reaction we
Scheme 7: Synthesis of articulated rods 32a–c (i: NaH, TMSCl, TMSOTf. ii: Cu/C, Et3N).
Scheme 8: Synthesis of articulated rods 33, 34 and 36.
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Beilstein J. Org. Chem. 2015, 11, 74–84.
first prepared the cinnamoyl substituted phosphane 38 from methylester hydrochloride (40) is acylated with anthracene-9-
(
2-hydroxyphenyl)diphenylphosphane (37). By heating 34 and acetic acid to give 41. After saponification of the ester the
8 in DMF for 3 h the AR 39 was obtained as result of a trace- potassium salt of the corresponding acid 42 was treated with
3
less Staudinger ligation, albeit with low yield (Scheme 9).
32c affording the articulated rod 43 in quantitative yield
Scheme 10).
(
As already mentioned, we were interested in articulated rods
whose folded-stretched equilibrium could be influenced by
The stretched–folded equilibrium of articu-
external stimuli. In order to realize this aim we chose metal lated rods
cations as triggers and imidazole moieties as chelating groups at The fundamental feature of articulated rods is the restricted con-
the ARs. The chelating event should be monitored by the influ- formational space with two dominating species: a stretched and
ence on the [4 + 4] cycloaddition of anthracene.
a folded conformation. This feature was concluded from Molec-
ular Dynamics (MD) simulation revealing a bimodal distribu-
The synthesis of such a fourfold functionalized AR is based on tion of the end-to-end distance of a model articulated rod. One
the natural amino acid L-histidine. In the first step histidine maximum is located around 17 Å and can be attributed to the
Scheme 9: Synthesis of articulated rod 39 (i: cinnamoyl chloride, DMAP, pyridine. ii: DMF 120 °C).
Scheme 10: Synthesis of functionalized articulated rod 43 (i: PYBOP, Et3N. ii: KOH, H2O. iii: 32c, quant.).
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Beilstein J. Org. Chem. 2015, 11, 74–84.
stretched conformation, whereas a second maximum around
Å corresponds to the folded species (for details see
7
Supporting Information File 1). The investigation and the
manipulation of the equilibrium between these types should
therefore facilitate very interesting applications for ARs. As
mentioned above, compound 32a can serve as a probe for this
equilibrium owing to the pyrene moieties. As many polyaro-
matic hydrocarbons pyrene possess a marked tendency to form
excimers in the excited state [23]. The broad and structureless
excimer emission at ca. 477 nm is red-shifted by more than
1
00 nm against the structured monomer emission at ca. 377 nm.
This conspicuous change in the fluorescence spectra permits the
investigation of the equilibrium between 32a-STR and 32a-
FOL (Scheme 11).
Figure 4: Fluorescence spectra of AR 32a in EPA at different tempera-
tures (c = 5·10−6 mol/L).
At first we investigated the influence of temperature and solvent
viscosity on the STR–FOL equilibrium. At room temperature a
ratio between the monomer and excimer emission IM/IEX of character of the excimer and suggests that the conformer 32a-
about 100:60 is observed (Figure 4, red curve). The ratio does STR is the global minimum. Based on these results we next
not change on dilution (1.5·10−5 mol/L → 1.1·10−6 mol/L) indi- investigated the IM/IEX ratio in a variety of solvents with
cating that excimer formation actually proceeds intramolecu- different viscosity [26]. In Figure 5 the IM/IEX ratio is repre-
larly [24]. It should be noted that the ratio IM/IEX is not iden- sented in dependence on the viscosity η. Two nearly linear
tical to the STR:FOL ratio because pyrene forms dynamic correlations are discernable. The first group (circles) with a
excimers, i.e., the excimer formation takes place after the exci- steep slope of the correlation line corresponds to aprotic
tation and there is a considerable thermodynamic driving force solvents, whereas the second group (triangles) with a signifi-
for the formation.
cantly lower slope is formed by protic solvents. Obviously
protic solvents substantially stabilize the folded conformation
On cooling to 0 °C the IM/IEX ratio is increased to 100:30 32a-FOL. This can be understood by considering the rather
Figure 4, green curve) and at 77 K in a solid EPA [25] matrix hydrophobic backbone of the ARs and the markedly smaller
(
the excimer emission completely disappears (Figure 4, blue surface of the FOL conformation. This behavior resembles
curve). This behavior underlines the above-mentioned dynamic folding of peptides and self-assembly of lipids.
Scheme 11: Stretched-folded equilibrium of pyrene labelled AR 32a.
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Beilstein J. Org. Chem. 2015, 11, 74–84.
Figure 5: Monomer–excimer ratio IM/IEX of the fluorescence of 32a
depending on solvent viscosity (DCE = 1,2-dichloroethane, DCM =
dichloromethane, ACN = acetonitrile).
Figure 6: Monomer–excimer ratio IM/IEX of the fluorescence of 32a
depending on the addition of cyclodextrines in MeOH (inset: low ratios
32a/CD).
It is well known that cyclodextrines (CDs), bearing a IM/IEX ratio (Figure 6, inset). The reason for this behavior
hydrophobic cavity and a hydrophilic exterior, are able to remains still unclear.
encapsulate small hydrophobic molecules [27]. Therefore we
hypothesized that CDs, which are threaded on articulated rods Recently we demonstrated that OSK rods are easily incorpo-
and thus form pseudorotaxanes [28], could influence the STR/ rated in biological membranes [11-13]. Because articulated rods
FOL equilibrium, because the folding should be impaired are easier synthetically accessible, especially with different
(
Scheme 12). Furthermore, we expected that the effect should groups at each end, and remarkably better soluble, we also
depend on the size of the cavity of the CDs. As expected, the investigated the interaction of ARs with micelles and artificial
addition of Me-β-CD (which was used instead of β-CD due to membranes. In aqueous environments the folded conformation
the scarce solubility of the latter) in MeOH clearly increases the of 32a predominates (indicated by an IM/IEX-ratio < 1, see
IM/IEX ratio (Figure 6, green curve) whereas α- and γ-CD (blue Figure 7).
and red curve) have hardly any influence on the fluorescence
spectra of 32a. Remarkably, low ratios of 32a and α- or Upon addition of the non-ionic surfactant Triton X-100 with
Me-β-CD, respectively, initially cause a slight decrease of the concentrations above the critical micelle concentration
Scheme 12: Formation of pseudorotaxanes from AR 32a and cyclodextrines.
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Beilstein J. Org. Chem. 2015, 11, 74–84.
investigated the photochemical behaviour of bis-cinnamoyl
substituted ARs 32b, 33a and 39 as well as of bis-anthracenyl
substituted ARs 33b and 43. Herein we will only present
preliminary orienting results, because the comprehensive
investigation of these photoreactive systems goes beyond the
scope of the present study and will be published elsewhere.
All of the cinnamoyl derivatives 32b, 33a and 39 are photo-
chemically reactive and both the UV irradiation spectra as well
as MS and NMR spectra of the crude product mixture suggest
that the formation of cyclic truxinates took place as the result of
intermolecular [2 + 2] cycloaddition. The photochemical re-
activity of these three compounds, which differ from each other
by the length and structure of the linker unit, varies consider-
ably. In Figure 8 the photochemical decay curves of 32b, 33a
and 39 as well as the irradiation UV spectrum of 32b are
depicted. It is clearly discernible that 32b is substantially more
reactive than 33a and 39.
Figure 7: Influence of Triton X-100 on the fluorescence spectra of 32a
in aqueous solution. 32a was added from a stock solution in MeOH to
HBS giving a concentration of 2 µM. The fluorescence spectra
(λex = 340 nm) were recorded in the absence (line 1) or in the pres-
ence of Triton X-100 at 0.007 % (w/v) (line 2); 0.013 % (w/v) (line 3)
and 0.02 % (w/v) (line 4) at 37 °C.
The anthracene substituted articulated rods 33b and 43 are also
(
ccmc = 0.24 mM [29]), the signal of the excimer emission photochemically reactive. Remarkably, the photodepletion of 43
completely disappears, pointing to an incorporation of the AR is distinctly accelerated in the presence of Ca2+ and Mg2+ ions
in micelles in the straight conformation (Figure 7).
indicating that the [4 + 4] cycloaddition is triggered by a com-
plexation of these ions by the imidazole moieties.
A similar behaviour is observed in the presence of the double-
stranded lipid DOPC, which typically forms vesicles with Conclusion
membrane double layers. To determine the orientation of 32a in We have developed articulated rods (ARs) as a new class of
the membranes quenching experiments with KI were under- molecular rods. The structure of our ARs is based on two (or
taken (for details see Supporting Information File 1). We found more) conformationally rigid oligospiroketal (OSK) rods, which
a rapid decrease of the pyrene fluorescence to ca. 50% at low are linked by a flexible joint. The deciding feature of ARs is the
KI concentrations whereas considerably higher KI concentra- equilibrium between two leading conformations: a straight
tions were required to quench the fluorescence below 50%. This (STR) and a folded (FOL) species. The joint contains a 1,2,3-
outcome clearly indicates that the AR is incorporated with a triazole moiety and the synthesis was carried out by copper
perpendicular orientation to the membrane surface. Finally, we catalyzed alkyne/azide cycloaddition (CuAAC). To obtain ARs
Figure 8: Comparison of photochemical reactivity of 32b, 33a, 39 (left). Irradiation UV spectrum of 32b in ACN (right, t = 0, 0.5, 1, 1.5, 2.5, 4, 8,
16 min).
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Beilstein J. Org. Chem. 2015, 11, 74–84.
1
4.Techen, A.; Czapla, S.; Möllnitz, K.; Budach, D.; Wessig, P.;
with arbitrary functionalities in the terminal positions we used
trimethylsilyl alkynes and primary alcohols as protected alkynes
and azides, respectively. Pursuing this approach we prepared a
variety of ARs with different groups in terminal positions. The
AR 32a, bearing pyrene moieties turned out to be a versatile
tool to investigate the STR/FOL equilibrium. We systemati-
cally investigated this phenomenon as a function of solvent
viscosity, cyclodextrine addition and in the presence of lipids
forming micelles and vesicles. In contrast to these noncovalent
STR–FOL transitions we also reported on first results with
respect to covalent fixation of the folded species by photochem-
ical [2 + 2] and [4 + 4] cycloaddition. In summary, articulated
rods have proven to be valuable alternatives to more rigid single
rods. Especially the modular synthetic approach should open up
many attractive applications.
Kumke, M. U. Helv. Chim. Acta 2013, 96, 2046–2067.
doi:10.1002/hlca.201200616
15.Wessig, P.; Gerngroß, M.; Pape, S.; Bruhns, P.; Weber, J. RSC Adv.
2014, 4, 31123–31129. doi:10.1039/C4RA04437A
16.Lahann, J., Ed. Click Chemistry for Biotechnology and Materials
Science; Wiley-VCH: Weinheim, Germany, 2009.
doi:10.1002/9780470748862
1
7.Shuto, S.; Ono, S.; Hase, Y.; Kamiyama, N.; Takada, H.;
Yamasihita, K.; Matsuda, A. J. Org. Chem. 1996, 61, 915–923.
doi:10.1021/jo9518056
1
8.Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem. 2002, 114, 2708–2711.
doi:10.1002/1521-3757(20020715)114:14<2708::AID-ANGE2708>3.0.
CO;2-0
1
2
2
2
2
2
9.Lipshutz, B. H.; Taft, B. R. Angew. Chem. 2006, 118, 8415–8418.
doi:10.1002/ange.200603726
0.Laurent, B. A.; Grayson, S. M. J. Am. Chem. Soc. 2011, 133,
1
3421–13429. doi:10.1021/ja2024355
1.Kobayashi, M.; Kurosu, M.; Wang, W.; Kitagawa, I. Chem. Pharm. Bull.
994, 42, 2394–2396. doi:10.1248/cpb.42.2394
Supporting Information
1
2.Köhn, M.; Breinbauer, R. Angew. Chem. 2004, 116, 3168–3178.
doi:10.1002/ange.200401744
Supporting Information File 1
Experimental procedures and compound characterization.
3.Bains, G. K.; Kim, S. H.; Sorin, E. J.; Narayanaswami, V. Biochemistry
2012, 51, 6207–6219. doi:10.1021/bi3005285
[http://www.beilstein-journals.org/bjoc/content/
4.Strictly speaking, the excited π-complex in 32a is not an excimer but an
exciplex.
supplementary/1860-5397-11-11-S1.pdf]
2
5.EPA = diethyl ether/isopentane/ethanol 5:5:2, [26].
6.Becker, H. G. O. Einführung in die Photochemie; Deutscher Verlag der
Wissenschaften: Berlin, 1991.
2
References
1
.
Tour, J. M. Chem. Rev. 1996, 96, 537–554. doi:10.1021/cr9500287
2
7.Del Valle, E. M. M. Process Biochem. 2004, 39, 1033–1046.
doi:10.1016/S0032-9592(03)00258-9
2.
Schwab, P. F. H.; Levin, M. D.; Michl, J. Chem. Rev. 1999, 99,
1
863–1934. doi:10.1021/cr970070x
2
8.Nakashima, N.; Kawabuchi, A.; Murakami, H.
J. Inclusion Phenom. Mol. Recognit. Chem. 1998, 32, 363–373.
doi:10.1023/A:1008084015958
3
4
5
6
7
8
9
1
1
.
.
.
.
.
.
.
Levin, M. D.; Kaszynski, P.; Michl, J. Chem. Rev. 2000, 100, 169–234.
doi:10.1021/cr990094z
Tour, J. M. Acc. Chem. Res. 2000, 33, 791–804.
doi:10.1021/ar0000612
2
9.http://www.piercenet.com/product/triton-x-100-detergent-solution
(accessed Oct 10, 2014).
Schwab, P. F. H.; Smith, J. R.; Michl, J. Chem. Rev. 2005, 105,
1197–1280. doi:10.1021/cr040707u
Sakai, N.; Mareda, J.; Matile, S. Acc. Chem. Res. 2005, 38, 79–87.
doi:10.1021/ar0400802
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1.Müller, P.; Nikolaus, J.; Schiller, S.; Herrmann, A.; Möllnitz, K.;
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3.Grimm, C.; Meyer, T.; Czapla, S.; Nikolaus, J.; Scheidt, H. A.;
Vogel, A.; Herrmann, A.; Wessig, P.; Huster, D.; Müller, P.
Chem. – Eur. J. 2013, 19, 2703–2710. doi:10.1002/chem.201202500
doi:10.3762/bjoc.11.11
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