Quantitative Kinetic Modeling in Photoresponsive Supramolecular Chemistry: The Case of Water-Soluble Azobenzene/Cyclodextrin Complexes

TLDR: The proposed procedure has been shown to be very robust and is applicable to any other photoresponsive host-guest system and to develop a relevant and reliable protocol applicable to all other types of complexes.

Abstract: Hydrophilic host-guest complexes, consisting of water-soluble azobenzene and α-, β-, or γ-cyclodextrins, have been proposed as a model to study supramolecular photoresponsive systems in aqueous environments through a full spectrometric approach combined with a simulation and data fitting methodology. Various essential and complementary spectroscopic techniques have been used: circular dichroism to determine whether the complex is formed or not, NMR for the stoichiometry elucidation, and UV-visible spectrophotometry to obtain the association equilibrium constant of each complex and the quantum yield for each photochemical process. A step-by-step fitting procedure is presented, which enables the determination of all thermodynamic and photokinetic parameters. A sequential methodology is applied to dissipate all uncertainties on the variability of the results and to develop a relevant and reliable protocol applicable to other types of complexes. The proposed procedure has thus been shown to be very robust and largely applicable to other photoresponsive host-guest systems.

Figures

Table 2. molar absorption coefficients obtained for free and complexed AZOt and AZOc at the two irradiation wavelengths (366 and 420 nm). The error indicates the variability observed on the absorption coefficients during the fitting procedure.

Table 3. Photochemical processes and quantum yields obtained at the two irradiation wavelengths. The error indicates the variability observed on the quantum yields during the fitting procedure.

Figure 1. Circular dichroism (up) and UV-Vis (down) spectra of a) AZOt@αCD (black), AZOt@βCD (red) and AZOt@γCD (blue) inclusion complexes and b) AZOt@βCD (red) and AZOc@βCD (orange) inclusion complexes.

Figure 4. up: Spectral evolution of the AZOt - AZOc isomerization under irradiation at 366 nm (left), 420 nm (middle), and 366 nm (right). [AZOt]0 = 5.45x10 -5 mol.L-1 ; The arrows indicate the sense of evolution of the spectrum, the vertical lines indicate the irradiation wavelengths. down: Absorbance at 366 and 420 nm for three successive runs starting from AZOt and irradiated at: = 366 nm (left), = 420 nm (middle), = 366 nm (right). Dots: experiment; continuous line: simulation.

Figure 3. Spectra evolution of a) [AZOt]0 = 5.5x10 -5 mol.L-1 with increasing CD ; b) [AZOt]0 = 5.3x10-5 mol.L-1 with CD and c) [AZOt]0 = 5.2x10 -5 mol.L-1 with CD and d) for [AZOc]0 = 1.04x10-5 mol.L-1 with CD. Evolution of e) A420 versus [CD] for AZOt ; f) A436 versus [CD] for AZOt ; g) A410 versus [CD] for AZOt ; h) A430 versus [CD] for AZOc. Open circles: experimental points; continuous line: simulation. The variations on UV-visible spectra upon the addition of CD are different for all the tested inclusion complexes. For CD, as already mentioned, the max shifts from 346 to 354 nm. Three isosbestic points are observed at 348, 392 and 460nm. These isosbestic points account for the exchange between two species only, free AZOt and CD complex. For CD, max slightly shifts from 346 to 345 nm and two isosbestic points appear at 284 and 470 nm. As already mentioned, the observation of isosbestic points in these 2.1 stoichiometry indicates that, in the concentration range explored, the amount of 1:1 complex that is transiently formed is undetectable.

Figure 2. Job plot of the different complexes a) AZOt in the presence of (red ○) and CD (blue ) and AZOc in the presence of CD (green Δ). b) AZOt in the presence of CD Maxima were found at R = 0.5, which suggests a 1:1 stoichiometry of the AZOt@CD, AZOt@CD and AZOc@CD host-guest inclusion complexes (Figure 2a). In a recent study,

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Quantitative kinetic modeling in photoresponsive
supramolecular chemistry: the case of water-soluble
azobenzene/cyclodextrin complexes
Jorge Royes, Camille Courtine, Corinne Lorenzo, Nancy Lauth de Viguerie,
Anne-Françoise Mingotaud, Véronique Pimienta
To cite this version:
Jorge Royes, Camille Courtine, Corinne Lorenzo, Nancy Lauth de Viguerie, Anne-Françoise Mingo-
taud, et al.. Quantitative kinetic modeling in photoresponsive supramolecular chemistry: the case of
water-soluble azobenzene/cyclodextrin complexes. Journal of Organic Chemistry, American Chemical
Society, 2020, �10.1021/acs.joc.0c00461�. �hal-02559449�

1
Quantitative kinetic modeling in photoresponsive
supramolecular chemistry: the case of water-soluble
azobenzene/cyclodextrin complexes
Jorge Royes
a,b ǂ
, Camille Courtine
a
, Corinne Lorenzo
b
, Nancy Lauth de Viguerie
a
, Anne-
Françoise Mingotaud
a,
*, Véronique Pimienta
a,
*
a
Laboratoire des IMRCP, Université de Toulouse, CNRS UMR 5623, Université Toulouse III -
Paul Sabatier, 118 Rte de Narbonne, F-31062 Toulouse cedex, France
b
ITAV, Université de Toulouse, CNRS, UPS, 1 place Pierre Potier 31106 Toulouse Cedex 1, France
ǂ
present address: PASTEUR, Dpartement de Chimie, cole Normale Supérieure, PSL University,
Sorbonne Universit, CNRS UMR 8640, 24 rue Lhomond, 75005 Paris France.
KEYWORDS (Word Style “BG_Keywords”). Host-guest, supramolecular, photochemistry,
azobenzene, cyclodextrin, modeling

2
TOC.
ABSTRACT (Word Style “BD_Abstract”). Hydrophilic host-guest complexes, consisting in a
water-soluble azobenzene and -, - or -cyclodextrins, have been proposed as a model to study
supramolecular photoresponsive systems in aqueous environments through a full spectrometric
approach combined to a simulation and data fitted methodology. Various essential and
complementary spectroscopic techniques were used: circular dichroism to determine whether the
complex was formed or not, NMR for the stoichiometry elucidation and UV-visible
spectrophotometry to obtain the association equilibrium constant of each complex and the quantum
yield for each photochemical process. A step by step fitting procedure is presented, which enables
the determination of all thermodynamic and photokinetic parameters. The sequential methodology
is applied in order to dissipate all uncertainties on the variability of the results and to develop a
relevant and reliable protocol applicable to other types of complexes. The proposed procedure has
thus been shown to be very robust and largely applicable to other photoresponsive host-guest
systems.

3
INTRODUCTION
Based on all recognition phenomena present in nature, host-guest interactions have been motivating
the chemists’ research for a long time, starting back in the 60s, with the early work of Cram,
Pedersen and Lehn and their Nobel Prize in 1987. Beside the synthesis of molecules with
programmed host-guest interactions, an essential part of supramolecular chemistry involves the
characterization of the produced complexes. For basic A/B complexes, two central parameters are
sought, namely the stoichiometry of the complex and its association constant. To determine these
parameters, linearization and graphical determination have long been used, especially the
continuous variation plots (so called Job’s plot) for the stoichiometry determination and Benesi-
Hildebrand linearization for the association constant
1
.
Cycodextrins (CD) are among the most popular supramolecular hosts
2
. Their high solubility in
water together with their central hydrophobic cavity make them interesting supramolecular hosts.
Various hydrophobic guests with different affinity to the CD inner pocket have thus been described,
ranging from adamantane to different aromatic molecules such as phenyl, naphthalene or ferrocenyl
moieties.
The interaction of photoreactive guests with CD may give rise to inclusion complexes, whose
formation and dissociation can be reversibly controlled through irradiation. For instance,
azobenzene derivatives-CD photoresponsive inclusion complexes have been known for more than
30 years
3
. From this time on, they have become a powerful building block to prepare advanced
materials with photomodulable properties. Indeed, the excellent biocompatibility of
azobenzenes@CD inclusion complexes makes them good photo-switches in the emerging field of

4
biointerfaces, or materials in contact with biological samples
4
. For example, self-healing materials
5
,
artificial muscles
6
, biomaterials with photomodulable mechanical properties
7
or drug controlled
release materials
8
have been described in the recent years.
Despite the numerous examples of azobenzene@CD complexes applications, there are only a few
quantitative studies about their photoisomerization mechanism. A couple of early works
characterized the photochemical
9
and thermal relaxation constants
10
of azobenzene@CD complexes
in different solvents. Later, Liu et al. studied the binding models and relative affinity of azobenzene
tethered cyclodextrins vs different aliphatic alcohol guests
11
. It is worth mentioning that all these
studies were carried out in organic solvents or aqueous mixtures of them due to the low solubility
of azobenzene compounds in water. This poor water solubility of azobenzenes@CD supramolecular
photoswitches is a strong limitation for biological applications. Different strategies to increase the
water solubility of the azobenzene@CD photoswitches have included grafting on hydrophilic
moieties, such as polyethyleneglycol
12
, polyacrylate
5, 13
, polysaccharides
7b
or peptides
14
, or
introducing charged moieties
15
such as ammonium
10, 16
or carboxylates
17
. All these studies are
however limited to the determination of the stoichiometry and affinity constant of the complex
formed by hydrophilic azobenzene derivatives as guests. Thus, there is a strong lack of thorough
characterization of the isomerization kinetics and related quantum yields for azobenzene@CD
complexes in water.
The purpose of this study was to fully characterize the complexation, kinetic and spectral properties
of a water soluble azobenzene compound (noted AZO) in presence of ,  and CD. A
quantitative approach of the photoisomerization processes in the presence of CD was obtained by
simulation and data fitting, following a step by step procedure described in scheme 1. We first
determined the stoichiometry and equilibrium complexation constants of the AZO compound in the

Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "Quantitative kinetic modeling in photoresponsive supramolecular chemistry: the case of water-soluble azobenzene/cyclodextrin complexes" ?

Hydrophilic host-guest complexes, consisting in a water-soluble azobenzene and -, or -cyclodextrins, have been proposed as a model to study supramolecular photoresponsive systems in aqueous environments through a full spectrometric approach combined to a simulation and data fitted methodology. A step by step fitting procedure is presented, which enables the determination of all thermodynamic and photokinetic parameters. 

Q2. What are the future works in "Quantitative kinetic modeling in photoresponsive supramolecular chemistry: the case of water-soluble azobenzene/cyclodextrin complexes" ?

The authors have applied this method to study for the first time the photochemistry of different azobenzene-cyclodextrin inclusion complexes, widely used for preparing photoactive biomaterials, in water. Indeed, the authors found that the affinity constants in water of AZOt @ βCD and AZOc @ βCD are similar, which can limit the potential applications of this supramolecular photoswitch.