Acidity control by on/off switching of an intramolecular NH···O hydrogen bond by E/Z photoisomerization of cinnamate framework

Article abstract of DOI:10.1246/cl.2009.666

Acidity control by photoswitching of intramolecular NH·· ·O hydrogen bond using E/Z photoisomerization of cinnamate framework was achieved. According to the photoisomerization, the distance between amide NH and carboxylic oxygen was disgregated, and an in

Full text of DOI:10.1246/cl.2009.666

666
Chemistry Letters Vol.38, No.7 (2009)
Acidity Control by On/Off Switching of an Intramolecular NHÁÁÁO Hydrogen Bond
by E/Z Photoisomerization of Cinnamate Framework
Takashi Matsuhira,1 Hitoshi Yamamoto,ꢀ1 and Taka-aki Okamura2
1Department for the Administration of Safety and Hygiene (DASH), Osaka University,
1-1 Yamadaoka, Suita, Osaka 565-0871
2Department of Macromolecular Science, Graduate School of Science, Osaka University,
1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043
(Received February 9, 2009; CL-090145; E-mail: jin@chem.sci.osaka-u.ac.jp)
X
Acidity control by photoswitching of intramolecular NHꢁꢁꢁO
X
O
O
hydrogen bond using E/Z photoisomerization of cinnamate
framework was achieved. According to the photoisomerization,
the distance between amide NH and carboxylic oxygen was dis-
gregated, and an intramolecular NHꢁꢁꢁO hydrogen bond formed
in E carboxylate was interrupted in Z compound in DMSO-d6
solution. The pKa value of Z carboxylic acid was increased in
E compound in DMSO solution.
O
O
H
h
ν
N
H
O
O
N
X = H
(E-1)
X = H
(Z-1)
X = NMe4 (E-2)
X = NMe ( -2)
Z
4
Scheme 2. ON ! OFF (E-1, Z-1, E-2, and Z-2) switching of
intramolecular NHꢁꢁꢁO hydrogen bond by E to Z photoisomeriza-
tion of cinnamate framework.
Native hydrolytic proteins rearrange the intramolecular
hydrogen bonds to carboxylate oxygens, to control the activity
of oxy-anions in their reaction center. They induce dynamic
switching of the overall protein structure triggered by external
stimulation to rearrange the hydrogen-bond network.1 We pro-
pose that the switching of intramolecular hydrogen bonding will
achieve control of the chemical properties of oxy-anion accom-
panied minimal conformation change by controlling the distance
between hydrogen-bond donors and acceptors in small mole-
cules.2 Photoisomerization, considered to be a promising strat-
egies for stimulating these compounds, effectively facilitates
the control of molecular structures. There have been many inves-
tigations using photoisomerization for photoswitching devices.3
For example, the effects of intramolecular OHꢁꢁꢁO, NHꢁꢁꢁN, and
NHꢁꢁꢁO hydrogen bonds in Z configuration on photoreactivity,4 as
well as the pKa change of phenol or carboxylic acid derivatives by
the switching of conjugation through photoisomerization5 have
been investigated. Hence we have applied photoisomerization
to design hydrogen bond switching devices.2 In a previous study,
the authors showed the OFF to ON one-way switching of an intra-
molecular NHꢁꢁꢁO hydrogen bond accompanying the E to Z pho-
toisomerization of a cinnamate framework (Scheme 1), and found
that NHꢁꢁꢁO hydrogen bonds formed in Z configuration lowered
the pKa value of the Z carboxylic acid derivative.2b The authors
conceived an idea that introduction of a carboxylic acid deriva-
tive into a cinnamate framework, and interruption of an intramo-
lecular NHꢁꢁꢁO hydrogen bond by photoisomerization (ON to
OFF switching), will increase the pKa value of the corresponding
carboxylic acid. Following this strategy, we designed ON !
OFF type compounds (E-1/Z-1 and E-2/Z-2) that interrupt
intramolecular NHꢁꢁꢁO hydrogen bonding through one-way E/Z
photoisomerization of a cinnamate framework (Scheme 2). The
formation of intramolecular NHꢁꢁꢁO hydrogen bonding in E
carboxylate ON ! OFF compounds showed promise in a previ-
ous investigation of a similar maleic amide skeleton.6
E-1 was synthesized through coupling of phenylmaleic an-
hydride and tert-butylamine. Z-1 was isolated from a photoreac-
tion mixture through addition of hydrochloric acid. E-2 and Z-2
were synthesized through a counter cation exchange reaction of
corresponding acids.7
E/Z photoisomerization was followed by UV–vis spectra
(Figure 1). Each E compound was isomerized and reached a pho-
tostationary state (PSS) at 313 nm irradiation. The absorbances
of E isomers decreased in accordance with a two state transition
upon irradiation, indicating that only the corresponding Z iso-
mers were formed without any side reactions. The E/Z ratios
in PSS were 15/85 (E-1/Z-1) and 16/84 (E-2/Z-2) respectively.
1H NMR spectra of carboxylates (E-2 and Z-2) in DMSO-d6
are shown in Figure 2. E/Z configurations were confirmed based
on NOE correlated spectroscopy (NOESY).7 NOE correlation
between olefin and phenyl protons were observed in E-2, where-
as correlation between tert-butyl and phenyl protons were ob-
served in Z-2. These correlations evidently confirm the configu-
ration around the allene. The amide NH chemical shift was
9.22 ppm in E-2 and 6.64 ppm in Z-2 at 303 K, and the temper-
ature dependency of the amide NH chemical shift of Z-2 was
ꢂ9:0 ppb Kꢂ1, whereas that of E-2 was ꢂ0:5 ppb Kꢂ1 in the
range of 303 to 333 K. The upfield shift (ꢀꢀ ¼ 2:58) and the in-
crease of temperature coefficient suggest that an intramolecular
NHꢁꢁꢁO hydrogen bond formed in E-2 was interrupted in Z-2.
An attempt was made to measure pKa values of E-1 and Z-1
by potentiometric titration in a 10% Triton X-100 aqueous mi-
O
O
O
O
H
H
N
hν
N
O
O
hyorogen bond
OFF
ON
Scheme 1. OFF ! ON one-way switching of an intramolecu-
lar NHꢁꢁꢁO hydrogen bond by E to Z photoisomerization of cin-
namate framework.2b
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.7 (2009)
667
Figure 1. Time course UV–vis spectra changes of (a) E-1,
(b) E-2, toward 313 nm photoirradiation (dotted lines), 1 mM
in DMSO at 293 K. Solid lines are those taken before irradiation,
and the broken lines are isolated Z compounds.
Figure 3. pKa differences of OFF ! ON and ON ! OFF type
carboxylic acids in DMSO solution on straight line, obtained
from H NMR analysis of ion-exchange reaction.
1
in OFF ! ON compounds, and raised in ON ! OFF com-
pounds, and the acidity was reversed after photoisomerization.
In conclusion, ON ! OFF photoswitching of an intramolec-
ular NHꢁꢁꢁO hydrogen bond by using E to Z photoisomerization
of a cinnamic acid framework was achieved. E-2 forms an intra-
molecular NHꢁꢁꢁO hydrogen bond in DMSO-d6 solution, and that
hydrogen bond is interrupted in Z-2, as a result of photoisomeri-
zation of the cinnamate framework. Consequently, the acidity of
the carboxylic acid was controlled arbitrarily by photoswitching
the intramolecular NHꢁꢁꢁO distances. Carboxylic acid com-
pounds that change chemical properties in response to external
stimulation could allow reactivity control by small molecules.
Figure 2. 1H NMR spectra of isolated carboxylate derivatives
a) E-2, b) Z-2, 5 mM in DMSO-d6 at 303 K.
cellar solution at 298 K. The pKa value of Z-1 was obtained as
4.3, but that of E-1 was not obtained accurately because of hy-
drolysis of the amide bond in aqueous micellar conditions.7 This
hydrolysis reaction does not proceed in organic solvents like
DMSO. Thus, we approached determination of relative acidity
in such an organic solvent. The differences of pKa values in or-
ganic solvent was obtained in accordance with a previous report
on related compounds.2b The counter cation exchange reaction
between two acids was examined, and the differences of pKa val-
ues in organic solvent were obtained from the deprotonation ra-
tio of two acids [Aꢂ]/[AH] and [BH]/[Bꢂ], from following
equations.
References and Notes
1
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2
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Keq
AH þ Bꢂ ꢀ Aꢂ þ BH
ð1Þ
ð2Þ
½Aꢂꢃ½BHꢃ ½Aꢂꢃ½Hþꢃ
½BHꢃ
Kað1Þ
Keq
¼
¼
ꢄ
¼
½AHꢃ½Bꢂꢃ
½AHꢃ
½Hþꢃ½Bꢂꢃ Kað2Þ
Carboxylic acid E-2 and carboxylate Z-1 were mixed in DMSO-
d6 solution and the equilibrium constant was confirmed from the
chemical shift of 1H NMR spectra.7 It was estimated that 75% of
the E compound was deprotonated, and 73% of the Z compound
was protonated, by comparing the chemical shifts with the isolat-
ed carboxylic acids and carboxylates. This result indicates that the
E compound has a pKa 0.92 unit lower than the Z compound in
DMSO solution. We propose that the interruption of intramolec-
ular NHꢁꢁꢁO hydrogen bonding in Z carboxylate discourages the
deprotonation and increases the pKa value of the corresponding
carboxylic acid Z-1. Estimating in a uniform manner, the Z con-
figured OFF ! ON compound has 1.63 unit lower pKa value than
the E compound,2b and the Z isomer has a 0.39 unit lower pKa val-
ue than Z-1, in DMSO solution.7 Figure 3 shows the pKa differ-
ences in DMSO solution as a straight line. Depending on photo-
isomerization, the pKa value of the carboxylic acid was lowered
4
5
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6
7
a) K. Takahashi, T. Okamura, H. Yamamoto, N. Ueyama, Acta Crys-
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The detail procedures of the synthesis, NOESY spectra, hydrolysis of
E-1, and the details of counter cation exchange reactions are described
in Supporting Information. Supporting Information is available elec-
tronically on the CSJ-Journal Web site, http://www.csj.jp/journals/
chem-lett/index.html.
Published on the web (Advance View) May 30, 2009; doi:10.1246/cl.2009.666