Solvatochromic probes for detecting hydrogen-bond-donating solvents

Article abstract of DOI:10.1039/c4cc00805g

Hydrogen bonding heavily influences conformations, rate of reactions, and chemical equilibria. The development of a method to monitor hydrogen bonding interactions independent of polarity is challenging as both are linked. We have developed two solvatochr

Full text of DOI:10.1039/c4cc00805g

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Solvatochromic probes for detecting
hydrogen-bond-donating solvents†
Cite this: Chem. Commun., 2014,
50, 4579
Ryan F. Landis,a Mahdieh Yazdani,a Brian Creran,a Xi Yu,a Vikas Nandwana,a
Graeme Cookeb and Vincent M. Rotello*a
Received 29th January 2014,
Accepted 14th March 2014
DOI: 10.1039/c4cc00805g
www.rsc.org/chemcomm
Hydrogen bonding heavily influences conformations, rate of reactions, of monitoring how hydrogen bonding influences overall structure,
and chemical equilibria. The development of a method to monitor independent of polarity, is therefore desirable.
hydrogen bonding interactions independent of polarity is challenging
Here, we report the development of organic dyes, 6-(3-amino-
as both are linked. We have developed two solvatochromic dyes that phenyl)-1,3,5-triazine-2,4-diamine (MADAT) and its acetylated analog,
detect hydrogen-bond-donating solvents. The unique solvatochromism AMADAT, which have the ability to detect hydrogen-bond-donating
of the triazine architecture has allowed the development of probes that solvents. While the emission shift of both MADAT and AMADAT is
monitor hydrogen-bond-donating species including water.
largely unchanged in all aprotic solvents regardless of polarity, these
dyes show a significant bathochromic shift in protic solvents. This
Solvatochromic probes are important in the study of solute– result shows the potential of these solvatochromic dyes to monitor
solvent interactions. The function of these probes depends on small changes in protic environments, independent of polarity, by
the overall solvation process around the solute.1 Solvent char- monitoring the bathochromic shift of their emission spectra.
acteristics, such as polarity and hydrogen-bonding, influence
Scheme 1 outlines the synthesis of MADAT and the acetylated
molecular conformations, reaction rates, and system chemical analogue, AMADAT. MADAT was synthesized by heating under reflux
equilibria.2 In addition, both polarity and hydrogen bonding 3-aminobenzonitrile with dicyandiamide in 1-butanol in the presence
are major contributors to the stabilization of protein folding and of a catalytic amount of potassium hydroxide.11 AMADAT was
binding sites.3 Previously, organic fluorescent dyes possessing synthesized by treating 3-aminobenzonitrile with acetic anhydride
solvatochromic properties have been used to investigate environ- in dichloromethane (DCM) to form N-(3-cyanophenyl)acetamide.
mental changes in biomembrane imaging,4 ion sensing,5 and Next, the acetamide and dicyandiamide was heated to reflux under
oil–water interface applications.6
the same conditions used to synthesize MADAT to form AMADAT.
The spectral shifts of current solvatochromic dyes are influenced By using commercially available materials, minimal steps, and a
by both dipole interactions and hydrogen bonding.7 These dyes simple purification protocol, large-scale synthesis of these dyes can
cannot distinguish between the two interactions, which makes be conveniently performed at a low cost.
assessing the response of each interaction to environmental change
difficult. This lack of specificity complicates the use of the dyes in
monitoring hydrogen-bond strengths,8 hydrogen-bond-based con-
formation changes,9 and detecting water and other hydrogen-bond-
donating species.10 Development of a solvatochromic dye capable
a Department of Chemistry, University of Massachusetts, 710 North Pleasant Street,
Amherst, Massachusetts, USA. E-mail: rotello@chem.umass.edu
b WestCHEM, School of Chemistry, Joseph Black Building, University of Glasgow,
Glasgow, G12 8QQ, UK
† Electronic supplementary information (ESI) available: Quantum yield of
MADAT in DCM and methanol. Emission of MADAT in phenol and trifluoro-
ethanol. AMADAT emission in various solvents. Linear correlation between
concentration of thymine 1 and fluorescence intensity. Addition of N-Me thymine
2 to MADAT in DCM. Linear relation between water concentration and fluores-
cence intensity. Concentration versus emission plots for MADAT and AMADAT.
Scheme 1 Synthetic steps to (a) MADAT and (b) AMADAT.
See DOI: 10.1039/c4cc00805g
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 4579--4581 | 4579

View Article Online
Communication
ChemComm
Fig. 2 Thymine 1 additions to MADAT [0.12 mM] in DCM. lex = 330 nm.
MADAT was subjected to additions of thymine 1 in DCM (Fig. 2).
As the concentration of 1 was increased, fluorescence quenching
along with bathochromic shifts were observed in the emission
spectra. These effects are attributed to the presence of three-point
hydrogen bonding between thymine 1 and the DAT ring of
MADAT.12 A linear correlation between the concentration of 1 and
the fluorescence intensity was observed (S3, ESI†). As a control, the
imide group of 1 was methylated before addition to MADAT in
DCM; in this case no quenching or shift was observed (S4, ESI†).
Since 1 can only bind to one DAT ring nitrogen atom due to steric
effects, we believe that large bathochromic shifts require multiple
hydrogen-bond interactions to occur with the triazine ring of
MADAT. The need for such multiple interactions would further
support the experimental results that showed a more significant
emission shift in protic solvents due to the small size of the solvent
Fig. 1 (a) Normalized absorption and (b) emission spectra of MADAT [0.22 mM],
[0.12 mM] (DCM) in various solvents. lex: aprotic = 330 nm, protic = 325 nm.
The influence of solvents on the spectroscopic properties of molecules and their ease of access to the nitrogen ring atoms.
MADAT was determined by UV-Vis absorption and fluorescence Kamlet–Taft plots are used to distinguish intermolecular
spectroscopy (Fig. 1). Minor changes in absorption spectra were interactions between solute and solvent.13 This method provides
observed (Fig. 1a) in either aprotic or protic solvents. In addition, the valuable data on how a solute interacts with solvent through both
emission spectrum of MADAT (Fig. 1b) was largely unchanged polarity and hydrogen bonding. MADAT can distinguish hydrogen
in aprotic solvents; however a significant bathochromic shift was bonding from polarity without the need for Kamlet–Taft plots in
seen in protic solvents. The same phenomenon was observed both a qualitative and quantitative manner. This solvatochromic
for AMADAT (S1, ESI†). Protic solvents dramatically affected the phenomenon can be useful in the detection of water in other
emission spectrum of these triazine dyes regardless of their media. As a proof of concept, MADAT was used to monitor water
chemical structure. Interestingly, strongly hydrogen bond levels in tetrahydrofuran (THF; Fig. 3). Emission of MADAT in
donating solvents such as phenol and trifluoroethanol resulted anhydrous THF was observed while adding small aliquots of
in complete quenching of MADATs emission (S2, ESI†).
water. Addition of water resulted in fluorescence quenching and
Emission shifts of solvatochromic materials are the result of a bathochromic shift in the emission spectra. A linear relation
environmental changes. As the material is excited by light, solvent between amount of water added and fluorescence intensity was
molecules align their dipoles with the solute. This realignment found (S5, ESI†), with a detection limit of detection of 0.014 wt%
can stabilize/destabilize and lower/raise the energy of emission and a quantification limit of 0.044 wt%.
from the solute, causing different light emissions from the same
In conclusion, new solvatochromic dyes demonstrate large
solute in different solvents. Since the emission of MADAT does bathochromic shifts of their emission spectrum in hydrogen-
not greatly shift in aprotic solvents regardless of polarity, there bond-donating solvents only, caused by the presence of the
may be no significant stabilization from the solvent or little charge 1,3,5 triazine moiety. These new types of probes therefore have the
separation within MADAT. The selective response of MADAT to potential to monitor hydrogen-bonding interactions independent
protic solvents could arise from hydrogen-bonding interactions of environmental polarity. We believe that a range of new solvato-
from the diamino units or the nitrogen atoms within the triazine chromic materials can be readily constructed using the triazine
ring. We hypothesize that the triazine ring serves as a multiple- architecture as modification of the aryl amine does not disrupt the
hydrogen-bond acceptor and is the cause of the large emission solvatochromic properties. This hydrogen-bond-selective solvato-
shift. Attention was first directed towards the amino groups of chromic feature could prove very useful in developing sensors for
MADAT to rule out hydrogen bonding at these positions. hydrogen-bond-donating species.
4580 | Chem. Commun., 2014, 50, 4579--4581
This journal is ©The Royal Society of Chemistry 2014

View Article Online
ChemComm
Communication
1
purification; H NMR (CD3OD, 400 MHz) d 7.71 (d, J = 1.2 Hz,
1H), 7.66 (s, 1H), 7.65 (d, J = 0.6 Hz, 1H), 7.34 (t, J = 1.8 Hz, 1H),
2.21 (s, 3H).
Synthesis of AMADAT: N-(3-cyanophenyl)acetamide (1.0 eq.,
3.0 g, 18.74 mmol) and dicyandiamide (1.2 eq., 1,891 g,
22.49 mmol) were dissolved in 1-butanol (100 ml) and solid
potassium hydroxide (0.2 eq., 0.150 g, 3.75 mmol) was added.
The mixture was heated to reflux under atmospheric conditions
for 18 h and cooled in an ice bath. Water (50 ml) was added to
fully precipitate the product. The precipitate was filtered off
and suspended in hot water (100 ml) and stirred for 5 min. The
precipitate was filtered and lyophilized to yield AMADAT (93%).
Mp 276–277 1C; e 1144 MÀ1 cmÀ1 (DCM), 1089 MÀ1 cmÀ1 (methanol);
1H NMR (CD3OD, 400 MHz) d 8.41 (s, 1H), 8.0 (d, J = 1.2 Hz, 1H),
Fig. 3 Changes in fluorescence emission of MADAT [0.22 mM] in THF
upon addition of water. lex = 330 nm.
All solvents and reagents were purchased from commercial 7.74 (d, J = 1.2 Hz, 1H), 7.41 (t, J = 2.4 Hz, 1H), 2.17 (s, 3H); 13C NMR
sources and were used as received, unless otherwise noted. (DMSO, 400 MHz) d: 170.73, 168.83, 167.85, 139.60, 138.18,
Deionized water was used in all steps where water was required. 128.83, 123.11, 122.31, 119.25, 24.40; HRMS m/z (M + H)+ calcd for
1H and 13C NMR spectra were recorded using a Bruker 400 MHz C11H12N6O: 245.10. Found: M + H = 245.5.
spectrometer. mM concentrations were used for absorption and
VR acknowledges funding from the NSF (CHE-1307021 and
emission spectra, unless otherwise noted. Absorption and emission CHE-1025889) and GC acknowledges the EPSRC.
measurements were performed on a Varian UV-Vis spectro-
photometer and a PTI fluorometer respectively using a quartz
cuvette.
Notes and references
Synthesis of 6-(3-aminophenyl)-1,3,5-triazine-2,4-diamine (MADAT):
To a solution of 3-aminobenzonitrile (1.0 eq., 5.0 g, 42.32 mmol)
and dicyandiamide (1.2 eq., 4.27 g, 50.79 mmol) in 1-butanol
(100 ml) was added solid potassium hydroxide (0.2 eq., 0.339 g,
8.464 mmol). The mixture was heated to reflux under atmospheric
conditions for 18 h. After the time allotted, the flask was cooled in
an ice bath and water (50 ml) was added to fully precipitate the
product. The precipitate was filtered off and suspended in hot
water (100 ml) and stirred for 5 min. The precipitate was filtered
and lyophilized to yield MADAT (89%). Mp 210–211 1C; e
2543 MÀ1 cmÀ1 (DCM), 1650 MÀ1 cmÀ1 (methanol); 1H NMR
(CD3OD, 400 MHz) d: 7.6 (s, 1H), 7.56 (1H, J = 1.2 Hz, 1H), 7.19
(t, J = 1.2 Hz, 1H), 6.88 (d, J = 1.8 Hz, 1H); 13C NMR (DMSO,
400 MHz) d: 171.40, 167.82, 148.87, 138.24, 128.93, 117.09,
116.20, 113.78; HRMS m/z (M + H)+ calcd for C9H10N6: 203.10.
Found: M + H = 203.10.
1 (a) K. Solnstev and D. Huppert, J. Phys. Chem. A, 1998, 102,
9599–9606; (b) C. Reichardt, Chem. Rev., 1994, 94, 2319–2358.
2 (a) C. Bohne, H. Ihmels, M. Waidelich and C. Yihwa, J. Am. Chem. Soc.,
2005, 127, 17158–17159; (b) A. Bergen, C. Bohne, D. Fuentealba,
H. Ihmels, T. Waidelich, C. Yihwa and J. Bats, Photochem. Photobiol.
Sci., 2012, 11, 752–767; (c) H. Ihmels, Eur. J. Org. Chem., 1999, 1595–1600.
3 C. Anfinsen, Science, 1973, 181, 223–230.
4 P. Yan, A. Xie, M. Wei and L. Loew, J. Org. Chem., 2008, 73,
6587–6594.
5 J. Wu, W. Liu, J. Ge, H. Zhang and P. Wang, Chem. Soc. Rev., 2011,
40, 3484–3495.
6 M. Vitha, ACS Symp. Ser., 2011, 1062, 51–97.
7 (a) A. Mehranpour and S. Hashemnia, J. Chin. Chem. Soc., 2006, 53,
759–765; (b) B. Hemmateenejad, M. Yazdani and H. Sharghi,
Spectrochim. Acta, Part A, 2012, 91, 198–205.
8 (a) P. Huynh, R. Walvoord and M. Kozlowski, J. Am. Chem. Soc., 2012,
134, 15621–15623; (b) M. Hao, J. Chem. Theory Comput., 2006, 2,
863–872; (c) A. Cuello, C. McIntosh and V. Rotello, J. Am. Chem. Soc.,
2000, 122, 3517–3521; (d) J. Carroll, M. Gray, K. McMenimen,
D. Hamilton and V. Rotello, Org. Lett., 2003, 5, 3177–3180;
(e) K. Matsubayashi and Y. Kubo, J. Org. Chem., 2008, 73, 4915–4919.
¨
9 (a) H. Bock, N. Nagel and C. Nather, Chem. – Eur. J., 1999, 5, 2233–2236;
Synthesis of N-(3-cyanophenyl)acetamide: 3-aminobenzonitrile
(1.0 eq., 5.0 g, 42.32 mmol) was dissolved in dichloromethane
(50 ml). Acetic anhydride (1.1 eq., 4.75 g, 4.40 ml, 46.55 mmol)
was added slowly to the stirred solution and allowed to react
overnight. The solution was concentrated under reduced pressure
and the mixture dissolved in ethyl acetate (100 ml). The solution
was cooled to 0 1C and saturated sodium bicarbonate was added
to the solution and allowed to stir for five minutes. The organic
layer was separated and washed twice with brine solution (50 ml).
The organic layers were combined, dried with sodium sulfate,
filtered, and concentrated under reduced pressure to yield
N-(3-cyanophenyl)acetamide (97%) and used without further
(b) P. Fita, M. Fedoseeva and E. Vauthey, J. Phys. Chem. A, 2011, 115,
2465–2470; (c) D. Cui, X. Qian, F. Liu and R. Zhang, Org. Lett., 2004, 6,
2757–2760; (d) M. Bonn, H. Bakker, A. Ghosh, S. Yamamoto, M. Sovago
and K. Campen, J. Am. Chem. Soc., 2010, 132, 14791–14978.
10 (a) M. Wolfshorndl, R. Baskin, I. Dhawan and C. Londergan, J. Phys.
Chem. B, 2012, 116, 1172–1179; (b) C. Pinheiro, J. Lima and
A. Parola, Sens. Actuators, B, 2006, 114, 978–983.
11 J. Shie and J. Fang, J. Org. Chem., 2003, 68, 1158–1160.
12 (a) B. Jordan, M. Pollier, Y. Ofir, S. Joubanian, J. Mehtala, C. Sinkel,
S. Caldwell, A. Kennedy, G. Rabani, G. Cooke and V. Rotello, Chem.
Commun., 2008, 1653–1655; (b) N. McDonald, C. Subramani,
S. Caldwell, N. Zainalabdeen, G. Cooke and V. Rotello, Tetrahedron
Lett., 2011, 52, 2107–2110.
13 M. Kamlet, A. Solomonovici and R. Taft, J. Am. Chem. Soc., 1979, 101,
3734–3739.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 4579--4581 | 4581