Hydrosulfide (HS?) Recognition and Sensing in Water by Halogen Bonding Hosts

Article abstract of DOI:10.1002/anie.202110442

Hydrogen sulfide (H₂S) plays a crucial signalling role in a variety of physiological systems, existing as the hydrosulfide anion (HS^?) at physiological pH. Combining the potency of halogen bonding (XB) for anion recognition in water

Full text of DOI:10.1002/anie.202110442

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Hydrosulfide (HS-) Recognition and Sensing in Water by Halogen
Bonding Hosts
Authors: Paul D. Beer, Edward J. Mitchell, Adam J. Beecroft, Jonathan
Martin, Sally Thompson, Igor Marques, and Vítor Félix
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202110442
Link to VoR: https://doi.org/10.1002/anie.202110442

10.1002/anie.202110442
Angewandte Chemie International Edition
COMMUNICATION
Hydrosulfide (HS-) Recognition and Sensing in Water by Halogen
Bonding Hosts
Edward J. Mitchell,[a] Adam J. Beecroft,[a] Jonathan Martin,[c] Sally Thompson,[c] Igor Marques,[b] Vítor
Félix[b] and Paul D. Beer*[a]
[a]
[b]
[c]
E. J. Mitchell, A. J. Beecroft, Prof. P. D. Beer
Department of Chemistry
University of Oxford
Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA (U.K.)
E-mail: paul.beer@chem.ox.ac.uk
Dr. I. Marques, Prof. V. Félix
CICECO – Aveiro Institute of Materials
Department of Chemistry
University of Aveiro
3810-193 Aveiro (Portugal)
Dr. J. Martin, Dr S. Thompson
Radioactive Waste Management
Building 329, Thomson Avenue, Harwell Campus, Didcot, OX11 0GD (U.K.)
Supporting information for this article is given via a link at the end of the document.
Abstract: Hydrogen sulfide (H2S) plays a crucial signalling role in a
variety of physiological systems, existing as the hydrosulfide anion
(HS-) at physiological pH. Combining the potency of halogen bonding
(XB) for anion recognition in water with coumarin fluorophore
incorporation in acyclic host structural design, the first XB receptors
to bind and, more importantly sense the hydrosulfide anion in pure
water in a reversible chemosensing fashion, are demonstrated. The
XB receptors exhibit characteristic selective quenching of
fluorescence upon binding to HS–. Computational DFT and Molecular
Dynamics simulations investigation in water corroborate the
experimental anion binding observations, revealing the mode and
nature of HS- recognition by the XB receptors.
bambusuril macrocycles in water.[14,15] A recent addition to the
anion-binding supramolecular toolbox is halogen bonding (XB), a
highly directional, attractive interaction between an electron-
deficient halogen atom, and a Lewis base.[16,17] The few acyclic
and macrocyclic XB receptors reported thus far commonly exhibit
superior anion binding affinities, as well as enhanced sensory
performance, compared to HB analogues,[18,19,20, 21] with examples
of XB host systems that function in aqueous media and especially
pure water being notably rare.[20,22]
Herein, we report the first XB receptors to recognise and
most importantly sense HS– in pure water using an optical
fluorescent chemosensing method. Three target XB host designs
(Figure 1) were developed, each containing two coumarin
fluorophores incorporated into a XB bis-iodotriazole pyridine,
pyridinium or secondary amine motif, where water solubility is
achieved by the functionalization of the coumarin groups with
multiple triethylene glycol (TEG) substituents.
Anions perform critical roles in a plethora of biological, medicinal
and anthropogenic environmental processes, inspiring the
burgeoning field of anion supramolecular chemistry.[1]
Overcoming competitive anion hydration is a key challenge in the
design of host systems capable of the molecular recognition of
anion guest species in aqueous media. Over the years highly
charged polycationic receptors, Lewis acidic main group and
metal based hosts, together with cyclic peptides and hydrophobic
cage-like hosts have been the leading effective strategies to
date.[1,2,3]
The toxicity of hydrogen sulfide (H2S) in the environment
and towards human health is well known. Furthermore, this simple
molecule has recently been recognised as a third gasotransmitter,
along with carbon monoxide and nitric oxide, playing crucial
signalling physiological functions in the regulation of
cardiovascular, immune, endocrine and nervous systems.[4-7] In
addition, abnormal H2S concentrations have been implicated in a
number of medical conditions.[8,9] With a pKa of 7.0, at
physiological pH, the hydrosulfide anion (HS-) is the dominant
species of H2S in aqueous solution. Methods for the detection of
these analytes have been mainly confined to irreversible
chemodosimeter approaches.[10,11] Surprisingly, it is only very
recently that a reversible supramolecular host-guest approach to
binding HS– has been reported in organic solvent media using
acyclic bis-urea[12] and tripodal amide receptors,[13] and with
Figure 1. Target water soluble halogen bonding host designs.
1
This article is protected by copyright. All rights reserved.

10.1002/anie.202110442
Angewandte Chemie International Edition
COMMUNICATION
The synthesis of the novel hosts is outlined in Scheme 1.
7-Hydroxycoumarin 1 was reacted with 1.2 equivalents of the
appropriate chloro-benzyl PEG functionalized derivative under
basic conditions in the presence of NaI to afford 2 in 75% yield.
Boc deprotection of 2 with TFA produced amine 3 which upon
sequential diazotization using NaNO2 and addition of NaN3 in
acidic aqueous solution afforded coumarin-azide 4 in yields of
94%. The copper (I) catalyzed azide-iodoalkyne cycloaddition
(CuAAC) reaction of two equivalents of coumarin-azide 4 with one
equivalent of 3,5-bis-iodoalkyne pyridine 5 or N-Boc-protected
bis-iodoalkyne 6 in the presence of a [Cu(CH3CN)4]PF6 catalyst
and TBTA afforded XB1 and Boc-protected bis-triazole derivative
7 in 75% and 59% yields, respectively. Methylation of XB1 to
produce the pyridinium receptor XB2 was achieved via reaction
with excess methyl iodide, followed by anion exchange with
sodium trifluoromethanesulfonate. Boc deprotection of 7 was
achieved using TFA to afford XB3.
Analogous synthetic methods were used to prepare the
corresponding hydrogen bonding hosts HB1-3 (Scheme 1). All
receptors were characterized by 1H and 13C NMR spectroscopy,
high resolution mass spectrometry, UV-Vis and fluorescence
spectroscopy (see SI).
The anion sensing properties of all receptors were investigated in
pH 7.4 aqueous HEPES buffer solution using fluorescence
spectroscopy.[23] At this pH value the protonated forms XB3H+ and
HB3H+ are the dominant receptor species present in the aqueous
solution.[24]
Figure 2. a) Fluorescence emission change of 10 µM XB1 on addition of NaHS
in pH 7.4 10 mM aqueous HEPES buffer solution b) Binding isotherms and
Bindfit analysis[25,26] fit of fluorescence titration data monitoring λmax (400 – 420
nm) of receptor XB1 upon addition of NaCl, NaBr, NaI and NaHS in pH 7.4 10
mM aqueous HEPES buffer solution.
The receptors’ fluorescence emission, following excitation at 342
nm, was monitored upon the addition of sodium hydrosulfide and
halide salts. Remarkably, the fluorescence intensity of XB1 was
significantly quenched by 60% in the presence of 10 equivalents
of HS-, while I-, Br- and Cl- induced no intensity diminutions (Figure
2a/2b and Figure S3-1). In stark contrast, HB1 exhibited only
minor fluorescence perturbations (Figure S3-2) suggesting very
weak binding which notably highlights the superior capability of
XB donor motifs for anion recognition and sensing in water in
comparison to HB donor analogues.
Scheme 1. Synthesis of receptors XB1–3 and HB1-3
2
This article is protected by copyright. All rights reserved.

10.1002/anie.202110442
Angewandte Chemie International Edition
COMMUNICATION
Similarly, addition of HS- to XB2 and XB3H+ caused notable
quenching, 45% and 38% respectively, whereas no change was
observed with Cl–. With XB2, both Br– and I– were sensed, with
the heavier halide also being detected by XB3H+ (Figure S3-5). In
contrast, the hydrogen bonding analogue HB3H+ was found to
display no fluorescent response to any anion (Figure S3-6).
However, HB2 exhibited a selective fluorescence intensity
decrease of 22% with addition of 100 equivalents of I- (Figure S3-
4). The quenching observed may be attributed to photoinduced
electron transfer (PET) between the coumarin fluorophore and the
bound anion.
of XB1-XB3, the respective receptor’s fluorescence returned to
near non-quenched emissions as ZnS precipitated, proving the
receptors’ chemosensing reversible capability (Figure S4-1).
The geometric and energetic properties of XB interactions
between HS- and I- with XB1 and XB2 were evaluated using DFT
calculations performed at M06-2X/Def2-TZVP/C-PCM (water) on
model complexes in which the large TEG substituted aryl moieties
were replaced with smaller ethyl groups, affording the XB1Et and
XB2Et prototypes (see SI for further computational details). The
optimised structures of the HS- and I- associations with XB1Et and
XB2Et are presented in Figure 3.
Bindfit analysis[25,26] of the titration data for XB and HB receptors
was used to determine 1:1 host:guest stoichiometric anion
association constants (Table 1).
Table 1. Anion association constants and limits of detection of HS- for receptors.
Host
Association constant Ka [M-1][a][b]
LoD
[µM]
Cl-
Br-
I-
HS-
16500
(1600)
XB1
XB2
NB
NB
NB
14.3
6.7
60800
(7800)
103000
(24000)
158000
(31000)
NB
NB
NB
NB
NB
Figure 3. DFT optimised structures of XB1Et and XB2Et model receptors
halogen bonded to HS- and I- anions. The XB interactions are sketched as
purple dashed lines.
46000
(14000)
5600
(530)
XB3H+
HB1
NB
NB
NB
NB
24.6
NB
NB
NB
NB
NB
The model receptors adopt a putative binding conformation with
the iodotriazole binding units establishing two convergent, almost
linear, XB interactions with C–I⋯I- and C–I⋯HS- angles around
171° (see Table S9-1). The I⋯SH- distances are markedly shorter
than the I⋯I- ones with average values of 3.173 ± 0.032 and 3.580
± 0.020 Å, respectively, mainly mirroring the ion volumes,
estimated as 58.78 Å3 for HS- and 70.48 Å3 for I-.[30] The XB
interactions are slightly shorter by ca. 0.05 Å in charged XB2Et
than in the associations with neutral XB1Et, regardless of the
anion. Noteworthy, the HS- anion is nearly perpendicular to the
iodotriazole binding units, intercepting the plane defined by the
two C–I bonds at a tilt angle of 90.7 and 93.0° for XB1Et, and
XB2Et , respectively, in agreement with the anisotropic distribution
of the electrostatic potential of HS- (see Figure S9-1). Overall, the
VS of the free XB-based model receptors yields well-defined
regions of high positive electrostatic potential in front of both
iodine binding sites (see Figure S9-2), enabling the anion
recognition through nearly linear XB interactions.
6080
(550)
HB2
NB
HB3H+
NB
NB
NB — No binding observed
LoD — Limit of Detection for HS-
[a] Anion association constants (with errors in brackets), determined using
Bindfit analysis[23,24] of the fluorescence titration data monitoring averaged λmax
(400 – 420 nm) [b] 10 µM receptors in 10 mM aqueous HEPES buffer solution,
pH = 7.4.
Notably, neutral XB1 behaves as an exclusive chemosensor for
HS-, exhibiting strong and selective recognition for HS- over the
halides, which are not bound. As expected, the magnitude of HS-
association by the positively charged pyridinium receptor XB2 is
significantly greater compared to neutral XB1 due to additional
favourable electrostatic interactions. However, the increase in
binding strength comes at the expense of a diminished degree of
selectivity for HS- as XB2 also binds Br- and, in particular, I-
strongly. XB3H+ exhibits impressive HS- selectivity over the lighter
halides but forms the strongest association with I-.[27,28]
The binding free energies (ΔGSS) between XB1Et or XB2Et and I-
or HS- were estimated as the energy differences between the
associations and the free model receptors and anions, as detailed
in the Supporting Information. The binding enthalpies (ΔH, given
in Table S9-2), of -13.91 and -16.30 kcal mol-1 for the HS-
associations with XB1Et, and XB2Et, are in line with the shorter
intermolecular distances computed for C–I⋯SH- halogen bonds,
while the I- associations. with the neutral and charged model
receptors. have ΔH values of -8.56 and -10.00 kcal mol-1,
respectively, mirroring the longer C–I⋯I- distances. The
estimative of the binding entropy penalties leads to the ΔGSS
values listed Table S9-2, which indicate an indubitable binding
preference of both model receptors for HS-, with a VS,min of -142.84
kcal mol-1. Moreover, the ΔGSS value of -0.77 kcal mol-1 for the
binding interaction between XB1Et and I- (with a VS,min of -125.35
Importantly, the limits of detection (LoD) for HS- for XB1-3 were
calculated to be in the low micromolar range (Table 1, Figure
S7-1), comparable to chemodosimeter probes used for detecting
H2S in aqueous environments and in vitro studies.[29]
However, in comparison to chemodosimeters, XB1-XB3 are
capable of acting as reversible chemosensors; reversibility
studies were carried out by removal of HS- using Zn(OTf)2. Upon
addition of the zinc salt to fluorescence HS- quenched solutions
3
This article is protected by copyright. All rights reserved.

10.1002/anie.202110442
Angewandte Chemie International Edition
COMMUNICATION
kcal mol-1) is almost negligible, in agreement with the inability of
neutral XB1 to bind this halide in water (see Table 1).
The strength of the XB interactions on the optimised model
complexes in water medium was further comprehensively
evaluated using different bond analysis methods. With the Natural
Bond Orbital (NBO) analysis,[31] the Second Order perturbation
theory interaction energies (E2) were estimated between the C–I
antibonding orbitals of the model receptors and the anions’ lone
pairs orbitals (nA → σ*C-I), together with the variations in the
occupancies of these orbitals. In agreement with interaction
energies, the E2 values listed in Table S9-3 show that the XB
interactions are stronger in the HS- associations with XB1Et, and
XB2Et, and naturally higher for the positively charged pyridinium-
based model receptor. Indeed, the E2 values for the individual
interactions with I- of 9.19 and 10.48 kcal mol-1 for XB1Et, and
XB2Et, respectively, are significantly smaller than the values for
the interactions with HS-, 17.45 and 21.16 kcal mol-1, in the same
order. These stronger interactions also lead to a change in the
σ*C–I orbital occupancies upon anion binding (see Table S9-3),
being more pronounced in the associations with HS-. Within the
scope of the Quantum Theory of Atoms in Molecules[32] (QTAIM),
the Potential energy density (V(r)) and Lagrangian kinetic energy
density (G(r)) of the XB interactions’ Bond Critical Points were
used to estimate the energies of these halogen bonds (see Table
S9-4).[33] The values of these two binding descriptors for a given
model receptor with HS- are ca. two times larger than with I-,
following the same trend of the E2 energies (R2 ≥ 0.99, see Figure
S9-3), showing the equivalency between the QTAIM and NBO
analyses. Furthermore, the |V(r)|/G(r) ratio gives insights into the
nature of the XB interactions.[34] Thus, the XB interactions of
XB1Et and XB2Et with I- are highly electrostatic, with ratios of ca.
0.93, while the interactions with HS-, with ratios around 1.04,
indicate a slight increase of the covalency degree on the
associations with this more nucleophilic anion (see Table S9-4).
Figure 4. Electron density difference maps for the XB2Et associations with HS-
and I- highlighting the superior electron transfer in the HS- host-guest
association.
The XB-based associations between HS- and I- and the complete
receptors were also investigated by Molecular Dynamics (MD)
simulations in water, carried out under periodic boundary
conditions, using classical force field parameters and an extra-
point of charge to represent the iodine binding units’ σ-holes (see
SI for remaining simulation details). Regardless of the anion-
receptor association, the XB interactions are maintained nearly
throughout the whole simulation time (see Table S9-6 for their
average dimensions). In addition, the halogen bonded HS- and I-
anions are surrounded by water molecules as shown for their
associations with XB2 in Figure 5 and in Figure S9-5 for their
associations with neutral XB1. Furthermore, the TEG chains
exhibited a large conformational flexibility along the MD runs,
indicating that they have no role in the shielding of the guest
anions from the solvating water molecules. A small decrease on
the average number of the anions’ surrounding water molecules
is observed when compared with the freely solvated anions, from
10.6 to 7.9 for HS- and from 7.7 to 6.0 for I- for an anion-water
distance cut-off of 3.5 Å (see Table S9-7 and Figure S9-6). This
result suggests that the water molecules play an important role in
the recognition of both anions. A deeper understanding of this
matter might be obtained from QM/MM MD simulations in water
with the XB associations, along with fewer water molecules
surrounding the anions (typically the first solvation sphere),
treated by QM methods. However, this robust and
computationally demanding approach falls beyond of the scope of
this communication.
The nature of the halogen bonds was also ascertained in gas-
phase through Symmetry-Adapted Perturbation Theory (SAPT)
analysis (see SI),[35] with the estimative of the electrostatic,
exchange, induction, and dispersion components of the SAPT
interaction energy (see Table S9-5). Regardless of the anion, the
electrostatic term is the largest component in the associations of
charged XB2Et, whilst for the complexes with neutral XB1Et it is
the repulsive exchange term. Moreover, within the attractive
components, the greater contribution to the stabilisation of the
binding interaction comes from the electrostatic interactions (ca.
46% in XB1Et; ca. 60% in XB2Et), followed by the induction forces
(ca. 36% in XB1Et; ca. 28% in XB2Et), and by the dispersive
contributions (ca. 19% in XB1Et; ca. 12% in XB2Et).
Figure 5. A snapshot of a MD simulation of HS- and I- associated with XB2,
showing the anions enclosed by water molecules and the random orientation of
the TEG flexible chains. Most hydrogen atoms were hidden for clarity.
Overall, the recognition of HS- and I- by the model receptors is
accompanied by a loss of electron density around the guest anion
and a gain of electron density along the iodotriazole binding units.
This is illustrated in Figure 4 and S9-4, where the changes in
electron density between the associations with HS- or I- and their
individual components are plotted (loss of electron density in blue
and gains in pink), being more prominent in the charged XB2Et.
In conclusion, XB anion recognition and reversible chemosensing
of HS- in pure water has been demonstrated for the first time. This
was achieved through the integration of coumarin fluorophores
into XB bis-iodotriazole pyridine, pyridinium and secondary amine
acyclic host structural frameworks, functionalised with hydrophilic
triethylene glycol (TEG) substituents. Importantly, XB1 exhibits
exclusive chemosensing behaviour for HS-, exhibiting strong and
selective recognition of HS-, over halide anions which are not
bound under aqueous buffered conditions. Selective binding of
4
This article is protected by copyright. All rights reserved.

10.1002/anie.202110442
Angewandte Chemie International Edition
COMMUNICATION
HS- was also displayed by XB2. In stark contrast, the HB receptor
analogues were incapable of functioning as chemosensors for
HS- under these competitive aqueous conditions. These results,
corroborated by computational methods, further advance and
highlight the potential of halogen bonding based sensor systems
for detecting anions in aqueous media.
[26] http://supramolecular.org/
[27] To rule out the possibility of HS- reacting with XB1, electrospray mass
spectrometry (EMS) experiments monitoring 10 µM XB1 in 10 mM
HEPES aqueous buffer (7.4 pH) in the presence of excess equivalents
of HS- were conducted, no evidence of reaction was observed. (Figure
S6-1)
[28] Titrations of buffered 10 µM receptor XB3 against NaOH revealed no
change in fluorescence (Figure S3-5).
[29] X. Wang, L. An, Q. Tian and K. Cuib, RSC Adv., 2019, 9, 33578-3
[30] T. Lu, F. Chen, J. Comput. Chem. 2012, 33, 580-592.
[31] F. Weinhold, C. R. Landis, Valency and Bonding: A Natural Bond
Orbital Donor-Acceptor Perspective, Cambridge University Press, 2005.
[32] R. F. W. Bader, Atoms in Molecules: A Quantum Theory, Oxford
University Press, 1991.
Acknowledgements
E. J. M. thanks the EPSRC and Radioactive Waste Management
for postgraduate funding. The computational studies were
supported within the scope of the project CICECO-Aveiro Institute
of Materials, UIDP/50011/2020, financed by national funds
through the Portuguese Foundation for Science and
Technology/MCTES.
[33] E. V Bartashevich, V. G. Tsirelson, Russ. Chem. Rev. 2014, 83, 1181–
1203.
[34] a) E. Espinosa, I. Alkorta, J. Elguero and E. Molins, J. Chem. Phys., 2002,
117, 5529–5542; b) R. Wang, J. George, S. K. Potts, M. Kremer, R.
Dronskowski and U. Englert, Acta Cryst., 2019, C75, 1190-1201; c)
|V(r)|/G(r) ratio values below 1 indicate a pure electrostatic interaction,
values greater than 2 are typical of covalent bonds and the values in-
between indicate an intermolecular interaction with an intermediate
character between ionic and covalent bonds.
[35] The SAPT calculations were performed with the Def2-TZVP basis set on
model complexes previously optimised in gas-phase at the M06-
2X/Def2-TZVP theory level. As expected, the model receptors’ binding
affinities for both anions are higher is the gas-phase, as the XB
dimensions have shorter C–I⋯SH- and C–I⋯I- distances. Nevertheless,
the interactions energies in gas-phase and in water follow the same trend
(see Tables S9-1 and S9-2).
Keywords: Halogen bonding • Molecular recognition •
Hydrosulfide • Coumarin • Fluorescent sensing
[1]
[2]
[3]
N. H. Evans and P. D. Beer, Angew. Chem. 2014, 126, 11908-11948;
Angew. Chem. Int. Ed. 2014, 53, 11716–11754.
H. Tien Ngo, X. Liu and K. A. Jolliffe, Chem. Soc. Rev, 2012, 41, 4928–
4965.
M. J. Langton, C. J. Serpell and P. D. Beer, Angew. Chem. 2016, 128,
2012-2026; Angew. Chem. Int. Ed. 2016, 55, 1974–1987.
R. Wang, FASEB J., 2002, 16, 1792–1798
[4]
[5]
[6]
[7]
[8]
[9]
R. Wang, Physiol. Rev., 2012, 92, 791–896.
D. J. Polhemus and D. J. Lefer, Circ. Res., 2014, 114, 730–737
J. L. Wallace and R. Wang, Nat. Rev. Drug Discov., 2015, 14, 329–345.
S. Singh and H. Lin, Microorganisms, 2015, 3, 866–889.
D. Wu, W. Si, M. Wang, S. Lv, A. Ji and Y. Li, Nitric Oxide - Biol. Chem.,
2015, 50, 38–45.
[10] N. S. Lawrence, J. Davis and R. G. Compton, Talanta, 2000, 52, 771–
84.
[11] Vivian S Lin, and Christopher J Chang, Curr Opin Chem Biol, 2012, 16,
595–601
[12] M. D. Hartle, R. J. Hansen, B. W. Tresca, S. S. Prakel, L. N. Zakharov,
M. M. Haley, M. D. Pluth and D. W. Johnson, Angew. Chem. 2016, 128,
11652-11656; Angew. Chem. Int. Ed. 2016, 55, 11480–11484.
[13] N. Lau, L. N. Zakharov and M. D. Pluth, Chem. Commun., 2018, 54,
2337–2340.
[14] J. Vázquez and V. Sindelar, Chem. Commun., 2018, 54, 5859–5862.
[15] H. A. Fargher, N. Lau, H. C. Richardson, P. H. Cheong, M. M. Haley, M.
D. Pluth, and D. W. Johnson, J. Am. Chem. Soc., 2020, 18, 8243–8251
[16] P. Metrangolo, F. Meyer, T. Pilati, G. Resnati, G. Terraneo, Angew.
Chem. 2008, 120, 6206-6220; Angew. Chem. Int. Ed. 2008, 47, 6114–
6127.
[17] G. Cavallo, P. Metrangolo, R. Milani, T. Pilati, A. Priimagi, G. Resnati and
G. Terraneo, Chem. Rev., 2016, 116, 2478–2601.
[18] A. Brown and P. D. Beer, Chem. Commun., 2016, 52, 8645–8658.
[19] J.Y. C. Lim and P.D. Beer, New J. Chem., 2018, 42, 10472-10475
[20] M. J. Langton, S. W. Robinson, I. Marques, V. Félix and P. D. Beer, Nat.
Chem., 2014, 6, 1039–1043.
[21] X. Li, J. Y. C. Lim, P. D. Beer, Chem. Eur. J, 2018, 24, 17788-17795
[22] A. Borissov, I. Marques, J. Y. C. Lim, V. Félix, M. D. Smith and P. D. Beer,
J. Am. Chem. Soc., 2019, 141, 4119–4129.
[23] Attempts to undertake 1H NMR anion titration studies with XB1 and XB2
receptors were thwarted by solubility problems with the respective
receptors being insufficiently soluble in D2O at the required mM
concentrations.
[24] The amine pKa of XB3 (10.29) and HB3 (9.98) were experimentally
determined by monitoring changes in fluorescence with pH. (Figure S5-1).
[25] D. Brynn Hibbert and P. Thordarson, Chem. Commun., 2016, 52, 12792–
12805.
5
This article is protected by copyright. All rights reserved.

10.1002/anie.202110442
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
Reversible chemosensing of hydrosulfide (HS–) in pure water is demonstrated using halogen bonding (XB) fluorescent hosts. The XB receptors
exhibit characteristic selective quenching of fluorescence upon binding HS– whereas the hydrogen bonding receptor analogues proved
incapable of functioning as chemosensors under aqueous conditions.
6
This article is protected by copyright. All rights reserved.