Benzene-based tripodal isothiouronium compounds as sulfate ion receptors

Article abstract of DOI:10.1016/j.tetlet.2003.11.048

Novel benzene-based tripodal isothiouronium receptors are synthesized for the selective recognition of tetrahedral oxoanions. The binding study by isothermal titration calorimetry indicates that the cationic receptors bind sulfate ions preferably in a tripodal mode, while they show a mixed binding mode toward phosphate ion. The tripodal isothiouronium receptors show large ΔG⁰ values toward sulfate ions in methanol, which are entropy driven. The results demonstrate that a subtle structural constraint can lead to different binding modes toward structurally similar anions.

Full text of DOI:10.1016/j.tetlet.2003.11.048

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 723–727
Benzene-based tripodal isothiouronium compounds as sulfate
ion receptors
Hye Ran Seong,a Dae-Sik Kim,a Sung-Gon Kim,a Heung-Jin Choib and Kyo Han Ahna,*
aDepartment of Chemistry and Division of Molecular & Life Science, Pohang University of Science and Technology,
San 31 Hyoja-dong, Pohang 790-784, South Korea
bDepartment of Industrial Chemistry, Kyungpook National University, Daegu 702-701, South Korea
Received 28 July 2003; revised 10 November 2003; accepted 13 November 2003
Abstract—Novel benzene-based tripodal isothiouronium receptors are synthesized for the selective recognition of tetrahedral
oxoanions. The binding study by isothermal titration calorimetry indicates that the cationic receptors bind sulfate ions preferably in
a tripodal mode, while they show a mixed binding mode toward phosphate ion. The tripodal isothiouronium receptors show large
DG0 values toward sulfate ions in methanol, which are entropy driven. The results demonstrate that a subtle structural constraint
can lead to different binding modes toward structurally similar anions.
ꢀ 2003 Elsevier Ltd. All rights reserved.
In nature, phosphate and sulfate binding proteins rec-
ognize the anions through multiple hydrogen bonds.1
Mimicking the nature, artificial receptors utilize hydro-
gen bonding as the main binding force for the recogni-
tion of these oxoanions. As the hydrogen bonding
donors, functional groups such as amide, sulfonamide,
urea, and thiourea have been widely used.2 Artificial
receptors with these neutral ligands, particularly tri-
podal receptors, have attracted much attention for the
efficient recognition of such tetrahedral oxoanions.3
Also, receptors with cationic ligands such as guanidi-
nium and isothiouronium have been studied for
enhanced binding affinity toward these anionic guests.4
Considering that phosphate and sulfate anions are tet-
rahedral, cationic tripodal receptors, given a 1:1 binding
mode, are more appealing than the corresponding
dipodal receptors. Surprisingly, cationic tripodal recep-
tors for tetrahedral oxoanions have received little
attention.5 Anslyn and co-workers have shown that
benzene-based tripodal receptors with guanidinium
ligands efficiently recognize anions such as citrate and
inositol phosphate.6 Because the benzene-based tripodal
system provides a preorganized ligand structure, it
would be interesting to develop related cationic recep-
tors toward the tetrahedral oxoanions.7 Herein, we wish
to report benzene-based tripodal isothiouronium com-
pounds as selective sulfate ion receptors.
We have chosen isothiouronium groups as hydrogen
donor ligands because both tripodal and luminescent
analogs8 can be readily synthesized from the corre-
sponding thiourea compounds. The benzene-based
tris(isothiouronium) receptors, BTT 1a and 1b,9 were
synthesized from the corresponding thiourea, which was
in turn prepared from mesitylene (Scheme 1). As a ref-
erence compound, we prepared a bis(isothiouronium)
analogue, BBT 2, similarly starting from 1,3-
bis(bromomethyl)mesitylene (Scheme 2).10 Hong and
co-workers showed that a related, but less preorganized,
dipodal isothiouronium receptor 3,4c which was syn-
thesized from the corresponding thiourea receptor 4,11
strongly bound dihydrogen phosphate.
NH(n-Bu)
NH(n-Bu)
N
H
S
N
H
S
Ar
HN
HN
2Br
Keywords: Anion recognition; Tripodal receptors; Thiouronium com-
pounds; Sulfate recognition; Preorganization.
Ar
S
NH(n-Bu)
S
NH(n-Bu)
* Corresponding author. Tel.: +82-54-279-2105; fax: +82-54-279-
3399; e-mail: ahn@postech.ac.kr
3, Ar = p-NO2-Ph
4
0040-4039/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.048

724
H. R. Seong et al. / Tetrahedron Letters 45 (2004) 723–727
Time (min)
80
NH2
Br
0
40
120
160
NH2
Br
b,c
a
4
H2N
Br
5
6
7
d
2
0
Ar
S
S
MeHN NH
NHMe MeHN NH
NHMe
S
N
H
S
N
H
e,f
Ar
3PF6
HN
HN
6
4
2
0
Ar
S
NHMe
S
NHMe
8
BTT 1a (Ar = Ph)
BTT 1b (Ar = 2-naphthyl)
Scheme 1. Syntheses of BTTs 1. Reagents and conditions: (a)
(CH2O)n, 30 wt % HBr/AcOH, 95 ꢁC, 12 h; (b) NaN3, acetone, reflux,
3 h, 90% for two steps; (c) LiAlH4, THF, reflux, 12 h, 81%; (d)
MeNCS, CH2Cl2, rt 3 h; (e) ArCH2Br, MeOH, reflux, 24 h, 91–100%
for two steps; (f) NH4PF6, MeOH, rt 24 h, 50–60%.
0.0
0.5
1.0
[SO42- ]/[1a]
1.5
2.0
2.5
3.0
NHMe
Br
N
H
S
2ꢁ
Figure 1. ITC titration data of BTT 1a with SO4 in MeOH at 303 K.
Ar
Br
HN
2PF6
9
Figure 1 shows typical calorimetric data (raw and inte-
2ꢁ 15
After
subtraction of heat of dilution from the raw data and
nonlinear curve fitting under Ôone set of sites modelÕ16
gave those thermodynamic parameters for the binding
process.
Ar
S
NHMe
gration data) obtained in the titration of SO4
.
BBT 2 (Ar = 2-naphthyl)
Scheme 2.
1
The H NMR spectrum of tris(thiourea) 8 exhibited a
C3-symmetric structure in CD3OD at ambient temper-
ature; however, those of BTTs 1 indicated slow equili-
bration of conformers, probably due to steric bulkiness
of the isothiouronium moiety. For example, BTT 1a
existed as two conformers in a ratio of ꢀ5:3, presumably
so-called ababab- and aaabbb-type conformers.12 These
conformer peaks merged into a C3-symmetric structure
upon raising the temperature over 60 ꢁC.
The DH0 and ꢁTDS0 data in Table 1 indicate that the
complex formation is driven mainly by favorable
entropy changes. Schmidtchen and co-workers already
pointed out that the binding of sulfate anion by guan-
idinium receptors in methanol is entropy driven.4e;f The
positive DH0 value in Table 1 reflects an endothermic
reorganization of the highly solvated host and guest
species in the protic solvent. The net increase of solvent
molecules liberated from these highly solvated species
before and after complex formation contributes to the
entropy increase, which outweighs the unfavorable
enthalpy change. The inflection point in the calorimetric
isotherm occurs near the molar ratio of 1.0, which cor-
responds to the host–guest stoichiometry n ¼ 1. Thus,
the cationic tripodal receptors 1a and 1b interact with
The formation of host–guest complex was supported by
2ꢁ
1H NMR analysis. For example, upon addition of SO4
in CD3OD, those broad and split peaks of BTT 1b due
to the conformational equilibrium merged into sharp
peaks, and also chemical shift changes occurred for
certain protons [–SCH2–: d 4.58 and 4.43 (m) fi 4.63 (s);
–CH2NH–: 4.94 and 4.90 (s) fi 4.88 (s) ppm for SO42ꢁ].
2ꢁ
SO4 in a 1:1 binding mode, as we intended in their
The binding characteristics of BTTs 1 and BBT 2
toward sulfate and phosphate anions were evaluated by
isothermal titration calorimetry (ITC).13 This ITC
analysis directly gives the standard enthalpy change
DH0, and estimation of DG0 and the host–guest stoi-
chiometry n by titration curve fitting. Thus, DS0 can also
be calculated from the Gibbs–Helmholtz equation. The
ITC measurements were carried out at 303 K in
MeOH.14 Tetramethylammonium salts of sulfate and
phosphate ions were used.
Table 1. Thermodynamic data for the host–guest complexation
determined by isothermal titration calorimetry
Entry
Guesta Host
nb
DG0c
DH0c
ꢁTDS0c
)14.7
)15.6
)14.8
2ꢁ
1
2
3
SO4
SO4
SO4
1a
1b
2
1.01
0.84
0.6
)8.3
)8.4
)6.0
+6.4
+7.2
+8.8
2ꢁ
2ꢁ
a Me4Nþ salts.
b Host–guest stoichiometry.
c Unit: kcal molꢁ1
.

H. R. Seong et al. / Tetrahedron Letters 45 (2004) 723–727
725
Time (min)
80
+
O
S
Me
0
40
120
160
L = HN
HN
O
O
L
L
SR
L
O
10
5
2+
RS
N
Me
Me
N
SR
N
H
H
O
N
N
H O
H
H
0
S
H O
O
H
N
H
25
20
15
10
5
N
N
SR
Me
Me
RS
Figure 2. Supposed binding modes for the 1:1 and 2:1 complexes of
2ꢁ
BTTs 1 and BBT 2 toward SO4
.
design. In contrast, in the case of BBT 2 a smaller DG0
value was obtained and the n value was fluctuated near
0.6. These results suggest that a 2H:1G complex may
form in the case of BBT 2 (Fig. 2).
0
0.0
0.5
1.0
1.5
2.0
2.5
[1a ]/[PO43-
]
3ꢁ
Similar ITC experiments toward PO4 gave different
results from those of SO42ꢁ. ITC titrations with BTT 1a
3ꢁ
Figure 4. The inverse titration data of BTT 1a with PO4 in MeOH at
303 K.
toward the PO4 ion17 suggest that a complex binding
3ꢁ
process is involved, in contrast to the case of SO42ꢁ. The
calorimetric raw data in Figure 3 suggests that the
binding process involves at least two equilibria since
more than single inflection points seem to exist.
(Fig. 5). Then, further addition of BTT 1a, after an
equivalent point, may not involve a marked solvent
reorganization through host–guest interactions, and
thus results in a small or little change in the binding
isotherm (Fig. 4). We carried out a similar inverse
3ꢁ
Since PO4 has multiple binding sites, we carried out
3ꢁ
Ôinverse titrationÕ using BTT 1a. Thus, a PO4 solution
2ꢁ
titration toward SO4 and observed nearly the same
behavior (1H:2G complex formation). The different ITC
in a calorimetric cell was titrated with BTT 1a. Non-
linear curve fitting under Ôone set of sites modelÕ pro-
vided DG0 ¼ ꢁ7:6 and n value of 0.6.18 Of notable is that
under the inverse addition mode larger heat evolution
results upon titrant injection (Fig. 4). From the inflec-
tion point, which is near n ¼ 0:5, a new 1H:2G binding
mode may be suggested in this case. Under the inverse
titration condition, we can expect that a relatively excess
amount of PO43ꢁ exists compared to BTT 1a at the initial
stage, and thus the 1H:2G complex may be formed
O
L
L
L
L
L
O
O
P
O
P
O
O
L
O
P
O
O
O
O
O
1H:2G complex
L
Inverse addition
L
L
Time (min)
0
40
80
120
160
8
6
4
2
0
1:1 and other
complexes
O
P
O
O
O
O
O
O
P
O
O
L
O
O
L
L
P
L
L
L
O
L
L
L
2H:1G complex
0.0
0.5
1.0
[PO43-]/[1a]
1.5
2.0
2.5
3.0
Normal addition
Figure 5. Initial binding modes depending on the inverse and normal
3ꢁ
3ꢁ
Figure 3. ITC titration data of BTT 1a with PO4 in MeOH at 303 K.
ITC additions in the case of PO4 (charge is omitted for clarity).

726
H. R. Seong et al. / Tetrahedron Letters 45 (2004) 723–727
results depending on the addition modes seem to be not
unusual in cases where both the host and guest have
multiple binding sites.
nition of tetrahedral oxoanions. Binding studies by
isothermal titration calorimetry in methanol indicate
that the cationic receptors bind sulfate ions preferably in
tripodal modes, while they bind phosphate ions in
complex modes. The different binding modes seem to be
originated from subtle structural complementarity due
to the ligand preorganization, in addition to the different
solvation energy in methanol. Studies toward preorga-
nized tripodal receptors with different ligands including
luminescence properties are under investigation.
To get additional information on the binding modes
depending on the guests, we carried out electrospray
ionization (ESI) mass analyses. We were able to confirm
a 1:1 host–guest complex formation between BTT 1a
2ꢁ
3ꢁ
and SO4 readily. Also, in the case of PO4 we were
able to observe a 1:1 host–guest complex albeit with low
intensity. However, attempts to observe other binding
modes such as 2H:1G or 1H:2G under various condi-
tions were not successful. We also attempted to get
binding information by NMR titration, but failed due to
small binding-induced chemical shifts and peak over-
lapping.
Acknowledgements
We thank the Korea Science and Engineering Founda-
tion (the Basic Research Program, grant no. R03-2001-
00032; R02-2002-000-00103-0) and the Center for Inte-
grated Molecular Systems for the financial support of
this work. We also thank Prof. Seung Koo Shin and
Mr. Hae Sung Lee for the ESI experiments.
The different binding behavior observed with BTTs 1
2ꢁ
3ꢁ
toward SO4 compared to PO4 may be related to the
structure complementarity between the host and guest.
The ÔcavityÕ of our tripodal receptor system seems to fit
2ꢁ
SO4 but does not match PO43ꢁ, probably owing to
larger size of the latter ion.19 Such subtle structural
selectivity may arise from a relatively rigid/preorganized
structure of the benzene-based tripodal system. In
addition to this structural effect, different solvation
energy between the two anions should be also an
important factor. An opposite guest selectivity was
observed in the cases of tripodal sulfonamide- and urea-
type receptors (10, 11) based on a flexible tris(2-amino-
ethyl)amine backbone, which was studied in an aprotic
solvent.3d;e
References and notes
1. (a) Luecke, H.; Quiocho, F. A. Nature 1990, 347, 402–406;
(b) He, J. J.; Quiocho, F. A. Science 1991, 251, 1479–1481.
2. For selected reviews on anion recognition, see: (a)
Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97,
1609–1646; (b) Beer, P. D.; Gale, P. A. Angew. Chem., Int.
Ed. 2001, 40, 486–516; (c) Gale, P. A. Coord. Chem. Rev.
2000, 199, 181–233; (d) Gale, P. A. Coord. Chem. Rev.
2001, 213, 79–128.
RHN
10, R = SO2R'
NHR
11a, R = C(O)NHR'
3. For tripodal neutral receptors for oxoanions, see: (a)
N
11b, R = C(S)NHR'
ꢀ
Raposo, C.; Perez, N.; Almaraz, M.; Luisa Mussons, M.;
Cruz Caballero, M.; Moran, J. R. Tetrahedron Lett. 1995,
ꢀ
NHR
36, 3255–3258; (b) Prodi, L.; Bolletta, F.; Montalti, M.;
Zaccheroni, N. Eur. J. Inorg. Chem. 1999, 455–460; (c)
Valiyaveettil, S.; Engbersen, J. F. J.; Verboom, W.;
Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1993, 32,
900–901; (d) Raposo, C.; Almaraz, M.; Martin, M.;
Recently, Hoffmann and co-workers reported a related
example in which the guest selectivity was changed
through conformational preorganization of a flexible
host.20 The structural factor seems to be very subtle: our
dipodal receptor BBT 2 shows a significant affinity
ꢀ
Weinrich, V.; Mussons, M. L.; Alcazar, V.; Caballero,
M. C.; Moran, J. R. Chem. Lett. 1995, 759–760; (e) Xie,
ꢀ
ꢀ
H.; Yi, S.; Wu, S. J. Chem. Soc., Perkin Trans. 2 1999,
2751–2754.
2ꢁ
toward SO4 but not toward PO43ꢁ, which makes it
4. (a) Ariga, K.; Anslyn, E. V. J. Org. Chem. 1992, 57, 417–
419; (b) Schiessl, P.; Schmidtchen, F. P. J. Org. Chem.
1994, 59, 509–511; (c) Yeo, W.-S.; Hong, J.-I. Tetrahedron
Lett. 1998, 39, 8137–8140; (d) Yeo, W.-S.; Hong, J.-I.
Tetrahedron Lett. 1998, 39, 3769–3772; (e) Berger, M.;
Schmidtchen, F. P. Angew. Chem., Int. Ed. 1998, 37, 2694–
2696; (f) Berger, M.; Schmidtchen, F. P. J. Am. Chem. Soc.
1999, 121, 9986–9993.
difficult to be determined by ITC. An opposite trend was
observed by bis(isothiouronium) receptor 3 that is
structurally very similar to BBT 2.4c In our case, the
presence of a methyl group between the two isothio-
uronium ligands in BBT 2 seems to cause a subtle
change in the bonding distance and angle in such a way
2ꢁ
3ꢁ
.
to accommodate SO4 better than PO4
5. Tripodal receptors with metal-centered coordination
bonds are used for phosphate recognition, see: (a) Kimura,
E.; Aoki, S.; Koike, T.; Shiro, M. J. Am. Chem. Soc. 1997,
119, 3068–3076; (b) Tobey, S. L.; Anslyn, E. V. Org. Lett.
2003, 5, 2029–2031; (c) Tobey, S. L.; Jones, B. D.; Anslyn,
E. V. J. Am. Chem. Soc. 2003, 125, 4026–4027.
6. (a) Metzger, A.; Anslyn, E. V. Angew. Chem., Int. Ed.
1998, 37, 649–652; (b) Niikura, K.; Metzger, A.; Anslyn,
E. V. J. Am. Chem. Soc. 1998, 120, 8533–8534; (c) For a
recent review on guanidinium-based receptors, see: Best,
M. D.; Tobey, S. L.; Anslyn, E. V. Coord. Chem. Rev.
The tripodal isothiouronium receptors 1a show a similar
level of affinity toward the sulfate ion as that of a
bis(guanidinium) receptor of Schmidtchen and
co-workers,4e from which we may expect a higher
affinity from a tripodal receptor based on the guanidi-
nium ligands.
In summary, novel isothiouronium-based tripodal cat-
ionic receptors are synthesized for the selective recog-

H. R. Seong et al. / Tetrahedron Letters 45 (2004) 723–727
727
€
2003, 240, 3–15; (d) For
a
benzene-based tripodal
1997, 53, 1647–1654; (c) Nishizawa, S.; Buhlmann, P.;
Xiao, K. P.; Umezawa, Y. Anal. Chim. Acta 1998, 358, 35–
44.
imidazolium receptor for halide recognition, see: Sato,
K.; Arai, S.; Yamagishi, T. Tetrahedron Lett. 1999, 40,
5219–5222.
12. For selected conformational arguments on the benzene-
based tripodal systems, see: (a) Kilway, K. V.; Siegel, J. S.
J. Am. Chem. Soc. 1992, 114, 255–261; (b) Hartshorn, C.
M.; Steel, P. J. Aust. J. Chem. 1995, 48, 1587–1599; (c)
Walsdorff, C.; Saak, W.; Pohl, S. J. Chem. Soc., Dalton
Trans. 1997, 1857–1861; (d) Hoskins, B. F.; Robson, R.;
Slizys, D. A. Angew Chem., Int. Ed. 1997, 36, 2752–2754.
13. (a) Christensen, J. J.; Wrathall, D. P.; Oscarson, J. O.;
Izatt, R. M. Anal. Chem. 1968, 40, 1713–1717; (b)
Smithrud, D. B.; Wyman, T. B.; Diederich, F. J. Am.
Chem. Soc. 1991, 113, 5420–5426.
7. Our own works on benzene-based tripodal receptors, see:
(a) Ahn, K. H.; Kim, S.-G.; Jung, J.; Kim, K.-H.; Kim, J.;
Chin, J.; Kim, K. Chem. Lett. 2000, 170–171; (b) Kim,
S.-G.; Ahn, K. H. Chem. Eur. J. 2000, 6, 3399–3403; (c)
Kim, S.-G.; Kim, K.-H.; Jung, J.; Shin, S. K.; Ahn, K. H.
J. Am. Chem. Soc. 2002, 124, 591–596; (d) Choi, H.-J.;
Park, Y. S.; Yun, S. H.; Kim, H. S.; Cho, C. S.; Ko, K.;
Ahn, K. H. Org. Lett. 2002, 4, 795–798; (e) Kim, Y. K.;
Ha, J.; Cha, G. S.; Ahn, K. H. Bull. Korean Chem. Soc.
2002, 23, 1420–1424; (f) Ahn, K. H.; Ku, H.; Kim, Y.;
Kim, S.-G.; Kim, Y. K.; Son, H. S.; Ku, J. K. Org. Lett.
2003, 5, 1419–1422; (g) Kim, S.-G.; Kim, K.-H.; Kim, Y.
K.; Shin, S. K.; Ahn, K. H. J. Am. Chem. Soc. 2003, 125,
13819–13824.
8. For luminescent sensors based on thiouronium and
thiourea receptors, see: (a) Kubo, Y.; Tsukahara, M.;
Ishihara, S.; Tokita, S. Chem. Commun. 2000, 653–654; (b)
Gunnlaugsson, R.; Davis, A. P.; Glynn, M. Chem.
Commun. 2001, 2556–2557; (c) Sasaki, S.; Citterio, D.;
Ozawa, S.; Suzuki, K. J. Chem. Soc., Perkin Trans. 2 2001,
2309–2313; (d) For a recent luminescent sensor for a
sulfate ion, see: Prohens, R.; Martorell, G.; Ballester, P.;
Costa, A. Chem. Commun. 2001, 1456–1457; (e) Nishiz-
awa, S.; Cui, Y.-Y.; Minagawa, M.; Morita, K.; Kato, Y.;
Taniguchi, S.; Kato, R.; Teramae, N. J. Chem. Soc.,
Perkin Trans. 2 2002, 866–870; (f) Kubo, Y.; Ishihara, S.;
Tsukahara, M.; Tokita, S. J. Chem. Soc., Perkin Trans. 2
2002, 1455–1460.
9. Selected spectroscopic data: 1a: 1H NMR (CD3OD,
300 MHz) d 9.7–8.9 (br m, 6H, –NH), 7.6–7.4 (m, 15H),
4.7–4.5 (m, 12H, –CH2–), 3.2 and 3.0 (br s, 9H, –NCH3),
2.2 (br s, 9H); 13C NMR (CD3OD, 75 MHz) d 165.8 and
165.6, 139.1, 134.8, 130.3, 129.2, 128.9, 128.2, 44.4 and
44.0, 36.0, 31.8 and 31.4, 16.3. 1b: 1H NMR (CD3OD,
300 MHz) d 9.7–8.9 (br m, 6H, –NH), 8.1–7.5 (m, 21H),
4.94 and 4.89 (s, 6H, –CH2N–), 4.58 and 4.43 (m, 6H,
–SCH2–), 3.2 and 3.0 (br s, 9H, –NCH3), 2.2–1.9 (m, 9H);
13C NMR (CD3OD, 75 MHz) d 165.8 and 165.5, 138.9,
132.8, 132.5, 130.1, 129.0, 128.7, 128.0, 127.7, 126.7, 126.6,
44.4 and 43.7, 36.3 and 35.8, 31.9 and 31.4, 15.9. 8: 1H
NMR (CD3OD, 300 MHz) d 7.36 and 7.24 (br s, 6H,
–NH), 4.57 (d, J ¼ 2:4 Hz, 6H), 2.96 (d, J ¼ 2:4 Hz, 9H),
2.43 (s, 9H, –ArCH3); 13C NMR (CD3OD, 75 MHz) d
183.0, 136.7, 132.8, 43.5, 30.7, 15.0.
14. A typical ITC experimental. A solution of (Me4Nþ)2SO4
2ꢁ
in methanol (2.0 mM) was introduced by 45 lL injections,
in total 200 lL, into a methanol solution of BTT 1a
(1.5 mL, 0.1 mM) in a calorimetry cell (Microcal Inc.). The
solution was kept at an operating temperature of 303 K.
Analysis and curve fitting using the software OriginTM
afforded the thermodynamic data.
15. The raw data in terms of microcalories/second plotted
against time cross over the zero level, owing to traces of
water remaining in the guest salt. Attempts to remove
water completely from the guest was not successful. All the
sample preparations were carried out in a glove box under
nitrogen.
16. The Ôone set of sitesÕ model applies for any number of sites
n if all sites have the same K and DH.
17. We prepared (n-Bu4Nþ)3PO4 by treatment of equimolar
3ꢁ
amounts of n-Bu4NOH and H3PO4 in methanol. We
found that attempted purification of the resulting salt by
recrystallization in various solvents (MeOH–Et2O,
MeOH–EtOAc, MeOH–CHCl3, MeOH–benzene, etc.)
was not reproducible or did not provide the desired salt.
The chemical entity of the salt was monitored by
volumetric titration. We found that mixing of equimolar
amounts of the reagents and subsequent evaporation of
the solvent under vacuum, without recrystallization, gave
the salt suitable for the ITC titrations.
18. Nonlinear curve fitting under conditions of two non-
identical and independent binding sites or two identical
and dependent sites model did not give better fit. Thus, the
DG0 value can be used only as an estimation.
ꢁ
19. The distance between the two oxygens of PhSO3 is
ꢁ
ꢁ
2.42 A, while that of PhP(OH)O2 is 2.55 A, see: (a) Kelly,
ꢁ
T. R.; Kim, M. H. J. Am. Chem. Soc. 1994, 116, 7072–
2ꢁ
3ꢁ
7078; (b) The thermochemical radii of SO4 and PO4
ꢁ
are 2.14 and 2.27 A, respectively, see: Solıs-Correa, H. J.
ꢀ
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