Luminescent iridium(iii)-boronic acid complexes for carbohydrate sensing

Article abstract of DOI:10.1039/d0dt02177f

A family of four Ir(iii) complexes of the form [Ir(ppy)2(L)]Cl (where ppy = 2-phenyl-pyridine and L = a pyridyl-1,2,4-triazole or pyridyl-1,3,4-oxadiazole ligand bearing a boronic acid group) have been prepared as potential luminescent sensors for carbohy

Full text of DOI:10.1039/d0dt02177f

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10.1039/D0DT02177F.
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14 March 2017
Pages 3073-3412
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Luminescent Iridium(III)-Boronic Acid Complexes for Carbohydrate Sensing
View Article Online
DOI: 10.1039/D0DT02177F
Tahmineh Hashemzadeh, Mohammad A. Haghighatbin, Johnny Agugiaro, David D. J. Wilson, Conor
F. Hogan and Peter J. Barnard*
Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe
University, Victoria, 3086, Australia, E-mail: p.barnard@latrobe.edu.au
Abstract
A family of four Ir(III) complexes of the form [Ir(ppy)2(L)]Cl (where ppy = 2-phenyl-pyridine and L
= a pyridyl-1,2,4-triazole or pyridyl-1,3,4-oxadiazole ligand bearing a boronic acid group) have been
prepared as potential luminescent sensors for carbohydrates. A modular eight step procedure was
developed to synthesise the complexes, and this was initiated with the preparation of two
benzhydrazide and three S-ethylated pyridine-2-thiocarboxamides precursors. Reaction of these
precursors produced three new 1,2,4-triazole- and one 1,3,4-oxadiazole -based ligands substituted
with boronic acid pinacol ester groups. The boronic acid pinacol esters were then converted to boronic
acids in two steps via potassium trifluoroborate intermediates. The boronic acid substituted ligands
and their Ir(III) complexes were fully characterised using a range of techniques including X-ray
crystallography in the case of the pyridyl-1,3,4-oxadiazole ligand and two of the Ir(III) complexes.
The capacity of the synthesised Ir(III) complexes to form boronic acid cyclic esters with the simple
sugars glucose and fructose was evaluated using high-resolution mass spectrometry (HRMS) and
photoluminescence titration studies. These studies confirm that the Ir(III) complexes form adducts
with both glucose and fructose, with increased levels of boronic acid cyclic esters being formed with
fructose at higher pHs. Theoretical calculations were used to gain insight into the nature of the
electronic transitions involved in the electronic absorption and emission spectra.
Introduction
Carbohydrates are components of many molecules that are fundamental to life such as DNA, RNA
glycolipids and glycoproteins.1 Carbohydrates are also important in disease diagnosis,2 for example,
unregulated levels of glucose in the blood are associated with the disease diabetes mellitus, which
can result in serious complications such as heart disease, stroke and kidney damage.3, 4 Additionally,
glycated proteins are known to be potential markers for a number of diseases such as cancer,
Alzheimer’s disease and autoimmune disease. The ability to selectively detect these species would
offer significant potential for the diagnosis and monitoring of the afore-mentioned conditions.5
A range of established methods are available to determine blood glucose concentrations, with many
of these approaches utilizing enzymatic reactions (e.g. glucose oxidase) in combination with

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electrochemical measurements.6 An alternative enzyme-free approach for sensing or imaging
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DOI: 10.1039/D0DT02177F
carbohydrates utilizes boronic acid containing molecules and materials in combination with
electrochemical, fluorescence or colorimetric measurements.1, 5 Boronic acids are excellent receptors
for carbohydrates (e.g. 1,2- or 1,3-diols) because the interaction is both rapid and reversible. Such
species have also shown significant promise for sensing and imaging more complex carbohydrates
and glycoproteins in cells.7, 8
In an effort to capitalise on these properties, an extensive range of luminescent organic molecules and
materials that incorporate boronic acid groups have been prepared as potential agents for imaging and
sensing carbohydrates.5, 9 In general, these carbohydrate sensitive boronic acid-based probes signal
the presence of carbohydrates such as glucose through either a change in their emission intensity or
wavelength.1, 5 Despite the large number of boronic acid containing probes that have been developed,
relatively few metal-based luminophores have been reported as carbohydrate sensors.10-16 The
structures of two metal-based luminescent carbohydrate sensors are shown in Figure 1. The Re(I)
complex I, showed pH dependent emission, as a result of a photoinduced electron transfer (PET)
mechanism. Addition of glucose to the complex in methanol caused an increase in the fluorescence
intensity, however the need for a pure organic solvent represents a significant drawback in terms of
potential biological applications.11 Addition of glucose to the Ru(II) complex II causes a quenching
of the luminescent emission as a result of cleavage of the 2-methoxyphenylboronic acid unit from the
complex.13
N
N
N
N
OH
B
O
O
N
N
OC
OC
N
N
N
Ru
N
Re
B
O
O
CO
MeO
I
II
Figure 1. Examples of luminescent metal complex-based sensors for carbohydrates.
We have a long-standing interest in the development and characterisation of new luminescent Ru(II)
and Ir(III) compounds, particularly of N-heterocyclic carbene ligands,17-20 for application as
electrochemiluminescent sensors21 and as luminescent imaging agents.22, 23 In the present paper, we
report the synthesis of a series of three pyridyl-1,2,4-triazole and one pyridyl-1,3,4-oxadiazole
ligands, which are substituted with boronic acid groups, together with their Ir(III) complexes. These
complexes were designed as potential luminescent imaging agents for sugars and carbohydrates based
on the well-known capacity of Lewis acidic boronic acids to form cyclic boronic acid esters with
sugars and carbohydrates in aqueous solution. The propensity of the Ir(III) complexes to form adducts

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with glucose and fructose esters was evaluated using high-resolution mass spectrometry (HRMS) and
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DOI: 10.1039/D0DT02177F
luminescence titration studies.
Results and Discussion
Ligand synthesis
A series of three 1,2,4-triazole-pyridine and one 1,3,4-oxadiazole -pyridine bidentate ligands bearing
boronic acid groups were prepared using a modular synthetic scheme. The synthesis was initiated
with the preparation of benzhydrazide 2a and a benzhydrazide substituted with a boronic acid pinacol
ester group at position 4 of the phenyl ring 2b (Scheme 1), via a nucleophilic acyl substitution reaction
between the ethyl ester compounds 1a and 1b with hydrazine hydrate.
O
O
O
EtOH, H2SO4
Reflux
NH2NH2 H2O
R
R
R
HO
H2N N
O
H
R = H
R = BO2C6H12
1a,
R = H, Ethylbenzoate, 92%
2a
2b
, R = H, Benzhydrazide, 85%
, R = BO2C6H12, 43%
1b
, R= BO2C6H12, 93%
Scheme 1. Preparation of benzhydrazide compounds 2a and 2b.
To synthesise the desired 1,2,4-triazoles, the thioamides 3a-3c (Scheme 2) were prepared utilizing a
convenient synthetic methodology described by Brooker and co-workers.24, 25 In this process the
required N-substituted pyridine-2-thiocarboxamide compounds were prepared by heating 2-
methylpyridine with the appropriate amine in the presence of sulfur and a catalytic amount of sodium
sulfide (Scheme 2). To increase the reactivity of the thioamides 3a, 3b and 3c towards nucleophilic
attack from the hydrazides 2a and 2b, the thioamides were S-alkylated with bromoethane in the
presence of sodium ethoxide yielding the S-ethylated products 4a, 4b and 4c as orange oils (Scheme
2).26 Due to their low stability and very unpleasant odour, these compounds were used promptly in
the following reactions without additional purification.
N
H
EtBr
N R'
R-NH2
N
N
R'
S8, Cat.
Na2S.9H2O
Reflux
N
NaOEt, EtOH
50 °C
S
CH3
S
R = Me
R = C6H5
R = C6H4BO2C6H12
4a
4b
4c
, R = CH3, 85%
, R = C6H5, 95%
, R = C6H4BO2C6H12, 96%
3a
3b
3c
, R = CH3, 21%
, R = C6H5, 71%
, R = C6H4BO2C6H12, 85%
Scheme 2. Preparation of N-substituted pyridine-2-thiocarboxamides, 3a, 3b and 3c and their S-
ethylated congeners, 4a, 4b and 4c.

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Reaction of the S-ethylated thioamides 4a and 4b with hydrazide 2a in 1-butanol generated the 1,2,4-
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DOI: 10.1039/D0DT02177F
triazoles 5a and 5b (Scheme 3). Similarly, compound 4c was reacted with hydrazide 2b yielding the
1
triazole 5d. H NMR spectroscopy and TLC analysis of the crude product formed in the reaction
between compounds 4b and 2a showed that two products were formed with one being the triazole
5b. Triazole 5b and the second product were separated by column chromatography and the unknown
compound was subsequently identified as oxadiazole 5c (Scheme 3). Compounds 5a-5d were
characterised using 1H and 13C NMR spectroscopy and these products showed the expected number
of signals consistent with their structures, with each bearing boronic acid pinacol ester units. In the
case of 5c, an X-ray crystal structure was also obtained (see Structural Studies section).
CH3
N
O
O
CH3
CH3
N
B
N
O
N
H2N N
O
B
n-butanol
S
H
N
N
O
5a
4a
, 43%
2a
O
O
O
N
N
N
O
N
O
B
N
N
B
B
H2N N
O
n-butanol
N
N
H
O
S
N
O
CH3
4b
5c
, 22%
2a
5b,
18%
R
N
O
N R
N
N
H2N N
n-butanol
N
S
CH3
H
N
4c
, R = C6H4BO2C6H12
2b
5d
, R = C6H4BO2C6H12, 46%
Scheme 3. Synthesis of 1,2,4-triazoles 5a, 5b, 5d and 1,3,4-oxadiazole 5c.
The formation of the oxadiazole product 5c is of interest as 1,3,4-oxadiazoles have not been
previously prepared via this synthetic approach. The abbreviated mechanism shown in Figure 2 is
proposed to account for the formation of this product. Here cyclisation results from attack of the
carbonyl oxygen of the hydrazide group on the carbon atom of the intermediate imine bond to form
the oxadiazole ring and subsequent loss of aniline yields the final boronic ester functionalised
compound 5c.

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O
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DOI: 10.1039/D0DT02177F
R
R
N
N
HN NH2
N
N
R
H
N
H
N
S
N
H
N
N
H
HS
N
2a
4b
O
O
N
O
O
N
HN
NH2
R
R
N
N
N
N
H
5c
, R= BO2C6H12
Figure 2. Abbreviated mechanism for the formation of oxadiazole compound 5c from hydrazide 2a
and 4b.
To prepare the desired ligands substituted with boronic acids, a two-step procedure was used to
convert the boronic acid pinacol ester units of compounds 5a - 5d, to boronic acids. In this procedure
the boronic acid pinacol ester was first converted to a trifluoroborate group (potassium salt) by
treating 5a – 5d with a saturated solution of KHF2 in methanol yielding compounds 6a – 6d (Scheme
4). The trifluoroborate group was then hydrolysed using LiOH and the desired 1,2,4-triazoles 7a, 7b,
7d, and the oxadiazole 7c functionalised with boronic acid groups were obtained in moderate yield
(Scheme 4).27 The 1H and 13C NMR spectra for 7a – 7d were consistent with the structures of these
compounds. In each case the 1H NMR spectra showed a broad peak in the region 8.15 – 8.33 ppm,
corresponding to the B(OH)2 group.

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R
N
R
N
R
N
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DOI: 10.1039/D0DT02177F
1) LiOH
O
N
Sat, KHF2
MeOH
N
N
B
3-K+
B(OH)2
BF
N
O
N
N
N
2) NH4Cl, HCl
N
N
5a
5b
, R = CH3
, R = C6H5
6a
6b
7a
7b
, R = CH3, 74%
, R = C6H5, 80%
, R = CH3, 59%
, R = C6H5, 65%
1) LiOH
Sat, KHF2
MeOH
O
N
O
O
O
N
N
3-K+
BF
B(OH)2
B
N
N
N
N
N
N
2) NH4Cl, HCl
O
5c
6c
, 77%
7c
, 52%
O
B
-
BF3 K+
O
B(OH)2
1) LiOH
N
N
Sat, KHF2
MeOH
N
N
N
N
N
N
N
N
N
N
2) NH4Cl, HCl
6d
7d, 47%
, 95%
5d
Scheme 4. Conversion of boronic ester groups of compounds 5a-5d to boronic acid units via
trifluoroborate intermediates.
Iridium complex synthesis
The cyclometalated Ir(III) complexes 8a – 8d were synthesised by the treatment of the chosen ligand
(7a – 7d) with the dimeric precursor complex [Ir(ppy)2Cl]2 (ppy = 2-phenylpyridine) in a mixture of
dichloromethane and ethanol (Scheme 5). The complexes were obtained in moderate to good yields
and were characterised by NMR spectroscopy and high-resolution mass spectrometry (HRMS) and
in the case of complexes 8a and 8c by X-ray crystallography (see Structural Studies section). The
high-resolution mass spectra of complexes 8a – 8d showed one major peak located at m/z = 781.2083,
843.2249, 768.1771, and 843.2245 respectively (Figure S7-S10, ESI) and in each case, these peaks
correspond to the exact mass of complexes (calculated masses: 781.2074, 843.2231, 768.1758, and
843.2231). The 1H NMR spectra for the complexes show a broad downfield shifted peak at 8.41, 8.26,
8.40, and 8.46 ppm for each of the complexes 8a – 8d corresponding to the boronic acid group.28

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DOI: 10.1039/D0DT02177F
N
Ir
R
N
N
N
N
[Ir(ppy)2Cl]2
B(OH)2
N
N R
CH2Cl2 /EtOH
N
N
N
Cl-
B(OH)2
7a
7b
, R = CH3, 59%
, R = C6H5, 65%
8a
8b
, R = CH3, 43%
, R = C6H5, 25%
N
O
N
Ir
N
[Ir(ppy)2Cl]2
B(OH)2
N
N
N
O
CH2Cl2 /EtOH
N
N
Cl-
B(OH)2
7c
, 52%
8c
, 85%
B(OH)2
N
Ir
N
[Ir(ppy)2Cl]2
B(OH)2
N
N
N
N
N
N
CH2Cl2 /EtOH
N
N
Cl-
7d
, 47%
8d
, 79%
Scheme 5. Synthesis of Ir(III) complexes 8a – 8d from boronic acid substituted ligands 7a – 7d.
Structural Studies
Single crystals suitable for X-ray diffraction studies were obtained for the 1,3,4-oxadiazole compound
5c and the Ir(III) complexes 8a and 8c, and the structures of these compounds are shown in Figure 3.
The X-ray crystal structure of 5c confirms that a 1,3,4-oxadiazole ring was formed and that this is
coupled to the pyridyl group and the phenylboronic acid pinacol ester unit at positions 2 and 5
respectively. The oxadiazole ring C-O bond distances are similar (C1-O1 = 1.3657(16) Å and C2-O1
= 1.3627(15) Å). The Ir(III) complex structures (8a and 8c) display slightly distorted octahedral
coordination geometries for the Ir(III) metal centres with two cyclometallating 2-(phenyl)pyridine
ligands and the 1,2,4-triazole-pyridine ligands. In each case, the pyridyl groups of the 2-
(phenyl)pyridine ligands adopt mutually trans dispositions respectively. The metal-ligand bond
distances for these complexes are given in Table 1 and the Ir–Ntriazole bond distance for compounds
8a is slightly shorter (2.095(3) Å) than the Ir–Noxadiazole bond distance (2.152(2) Å) found for
compound 8c. These bond distances are similar to those reported previously for related Ir(III)
complexes. For example, the Ir–Ntriazole bond distance for the Ir(III) complex of the ligand 2-[3-

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(trifluoromethyl)-1,2,4-triazol-5-yl]pyridine is 2.116 Å,29 while the Ir–Noxadiazole bond distance for the
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30
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Ir(III) complex of 2‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)pyridine is 2.158 Å. In the case of compound
8a, hydrogen bonding interactions are evident, with the O-H groups of the boronic acid being
hydrogen bonded to the chloride anion and a water molecule (Figure 3b). In the case of the oxadiazole
complex 8c, the X-ray quality crystals were obtained from a solution of the complex in methanol and
as a result of this choice of solvent the boronic acid group has been converted to a monomethyl
boronic acid ester. The remaining boronic acid O-H group is hydrogen bonded to the chloride anion
with the distance (O2-Cl1) being 3.062 Å.
Table 1. Selected bond distances (Å) from the X-ray structures of iridium(III) complexes 8a and 8c.
Bond
8a
8c
Ir-N1
Ir-N3
Ir-N4
Ir-N5
Ir-C14
Ir-C25
2.095(3)
2.173(3)
2.035(4)
2.049(3)
2.013(4)
2.014(4)
2.152(2)
2.193(2)
2.050(2)
2.053(2)
2.009(2)
2.011(2)

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Figure 3. Single crystal diffraction structures of the (a) 1,3,4-oxadiazole compound 5c and the Ir(III)
complex (b) 8a and (c) 8c. Solvent of crystallization omitted for clarity (except for 8a) and ellipsoids
are shown 40% probability.
Photoluminescence studies
The photophysical properties of Ir(III) complexes 8a-8d were evaluated and the UV-visible spectra
for these complexes are shown in Figure 4a. On the basis of theoretical studies (see Theoretical
Calculations section) and comparison with previously reported Ir(III) complexes31, 32 the intense
absorption bands at shorter wavelength (~260 nm) can be assigned to ligand-to-ligand charge transfer
(LLCT), while, the less intense bands at lower energies (>300 nm) are best assigned to admixed ligand
centred (LC) and metal to ligand charge transfer (MLCT) transitions. The absorption spectrum for
complex 8c (oxadiazole ligand) is different to the other complexes with a second prominent
absorption band centred at ~300 nm. The photoluminescence spectra for complexes 8a-8d are shown
in Figure 4b. The emission spectra are similar for all complexes with one broad emission band centred
at ~590 nm (ex = 346 nm). Such broad unstructured emission is consistent with a MLCT or LLCT
excited state, as predicted by the theoretical studies vide infra.

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Figure 4. (a) The UV-Vis absorption spectra and (b) photoluminescence emission spectra for
complexes 8a (blue), 8b (pink), 8c (green) and 8d (purple). The concentration in each case is 20 μM,
in aqueous tris-buffered solutions at pH = 9. The spike at 569 nm is an instrumental artefact due to
the switch between diffraction gratings at that wavelength.
Mass Spectrometric Boronic acid Sugar Binding studies
The boronic acid substituted complexes 8a-8d were prepared as potential luminescent sensors for
carbohydrates33-35 and in an initial study, the capacity of complex 8d to bind to the sugars fructose
and glucose was evaluated using high-resolution mass spectrometry (HRMS). Glucose and fructose
were chosen for these studies due to their significant biological importance and because boronic acid-
based sensors often display different binding affinities for these sugars,5 thereby allowing for an initial
assessment of the sensitivity and selectivity of these complexes. These initial measurements were
made at pH=7 and 9 as it has been shown previously that the capacity of boronic acid containing
compounds to bind carbohydrates via cyclic boronic acid ester formation is pH dependent, with the
tetrahedral boronate species formed at higher pH values (>9) facilitating boronic ester formation when
compared to the corresponding boronic acids.34, 36 The HRMS spectra for complex 8d in the presence
of fructose at pH 7 and 9 are shown Figures 5a and b respectively, while the spectra obtained for 8d
in the presence of glucose at pH 7 and 9 are shown in Figures 5c and d, respectively.

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Figure 5. High resolution mass spectra recorded for complex 8d in the presence of (a) fructose
(pH=7), (b) fructose (pH =9), (c) glucose (pH=7) and (d) glucose (pH=9). [8d] = 1.48  10-4 M,
[sugar] = 1.48  10-3 M.
The spectra shown in Figure 5 for compound 8d in the presence of fructose (a, pH=7 and b, pH=9)
and glucose (c, pH=7 and d, pH=9) show two main peaks, the first at m/z = 843.22 corresponds to the
complex cation while the second at m/z = 987.27 corresponds to the mass of the cyclic boronic acid
esters formed from these sugars (both fructose and glucose have the same molecular weight: 180.16
g/mol). The spectra obtained for 8d in the presence of fructose (Figure 5a and b) show a significantly
more intense peak is obtained for the boronic acid cyclic ester for this sugar when compared to
glucose. This result indicates that the complex forms an adduct with fructose more readily than with
glucose and this is consistent with a number of previous studies, which show that boronic acid sensors
more readily form boronic acid esters with fructose33, 34, 37 than glucose.38 The spectra shown in Figure
5 also demonstrate that the solution pH also has a strong effect on sugar-adduct formation, with higher
levels of the sugar adducts formed at elevated pH (e.g. pH=9). Again, this finding is consistent with
previous studies that show that the boronate anion (formed at higher pH when the Lewis acidic

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boronic acid reacts with hydroxide anions) reacts more readily with diols to form boronic acid cyclic
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esters.34, 36
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Luminescent Titration Sugar Binding Studies
Luminescent titration studies were conducted for the Ir(III) complexes with increasing ratios of the
sugars fructose and glucose. For complexes 8a-8c these studies were conducted at pH=9, while for
8d the studies were conducted at pH = 7 and 9. The results for complex 8d are shown in Figure 6
while the results for complexes 8a-8c are given in Figure S11 (ESI). Complex 8d exhibits a broad
emission centred at ~590 nm (ex = 346 nm) in tris buffer (20 mM) at pH = 7 and 9. The addition of
an increasing molar ratio of fructose (0 → 2 molar equivalents) to a solution of 8d at pH = 7 (Figure
6a) resulted in a modest 9% quenching of the luminescent emission band at 590 nm. In contrast, when
the same additions were made to 8d at pH = 9 (Figure 6b), a significantly greater quenching (39%)
of the emission band was observed. As was also seen in the mass spectrometric studies, it is apparent
that lower levels of the boronic acid cyclic ester is formed between complex 8d and glucose than for
fructose. The addition of glucose (0 → 2 molar equivalents) to 8d at pH = 7 and 9 resulted in moderate
quenching of the emission band with values of 11% and 14% respectively. Similar results are
observed for the UV-visible absorption spectra for complex 8d. A decrease in the absorptivity of the
complex is observed (particularly for the intense band centred at ~260 nm) with the addition of
fructose (Figure S12a and b) and glucose (Figure S12c and d, ESI), with these effects mirroring the
changes seen in the emission spectra. The titration results for complexes 8a-8c (Figure S11, ESI)
show only relatively low levels of quenching of the emission spectra in the presence of either fructose
or glucose.
These results suggest that the position of the boronic acid group is critical to the ability of these
compounds to act as luminescent receptors for sugars. When the phenyl ring bearing the boronic acid
group is coupled to N4 of the triazole ring (as is the case for 8d) a significant sensitivity of the
emission intensity to the presence of fructose (at pH=9) is observed. In contrast, for complexes where
the phenyl ring is coupled to a carbon atom (C3 for the 1,2,4-triazoles or C2 for the oxadiazole) a
considerably lower sensitivity to the sugars is observed. Although the mechanism of fluorescence
quenching for these complexes has not been investigated, similar results have been previously
reported for boronic acid-based carbohydrate sensors.1 For example, in an early study by Yoon and
Czarnik, an anthracene boronic acid-based sensor showed fluorescence quenching, with increased
quenching levels observed at higher carbohydrate concentrations and pH values as a result of an
excited state internal charge transfer (ICT) process.33 These results are similar to those obtained in
the present study and were attributed to the increased propensity of the boronic acid cyclic ester to
form the corresponding borate anions compared to the boronic acid. With the sp3 hybridised anionic

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borate species being less fluorescent than the sp2 hybridised boronic acid or cyclic boronic acid ester
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forms.33
DOI: 10.1039/D0DT02177F
Figure 6. Luminescent titration of compound 8d with the sugars (a) fructose pH = 7; (b) fructose pH
= 9; (c) glucose, pH = 7 and (d) glucose pH = 9. [Complex] = 20 M, [tris buffer] = 2.0 mM. The
spike at 569 nm is an instrumental artefact due to the switch between diffraction gratings at that
wavelength.
Theoretical Studies
The optimized geometries of complexes 8a-8d yield similar Ir-C and Ir-N bond distances (Table 2),
with bond distances for compounds 8a and 8c being in good agreement with the X-ray structures
(Table 1).

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Table 2. mPW1PW91/def2-SVP calculated bond distances for Ir-C and Ir-N bond for complexes 8a-
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DOI: 10.1039/D0DT02177F
8d (Å).
Bond
Ir-N1
Ir-N3
Ir-N4
Ir-N5
Ir-C14
Ir-C25
8a
8b
8c
8d
2.153
2.213
2.062
2.063
2.012
2.008
2.150
2.218
2.066
2.065
2.013
2.008
2.168
2.237
2.065
2.065
2.008
2.007
2.150
2.218
2.065
2.065
2.013
2.007
Plots of the frontier molecular orbitals (MOs) for 8a-8d are shown in Figure 7. For each complex, the
HOMO is centred on the metal and phenylpyridine (C^N) ligands, while the LUMO (and LUMO+1)
is located on the auxiliary N^N ligand. For compounds 8a-8c there is a non-negligible contribution
to the LUMO from the phenyl group of the boronic acid moiety, which is absent in 8d.
Figure 7. Plots of BP86/def2-TZVP calculated molecular orbitals of complexes 8a-8d.
Analysis of the frontier MOs was carried out to characterise orbitals according to their Mulliken
population from molecular fragments of the metal, N^N coordinated, and C^N coordinated ligands,
with results for complexes 8a-8d plotted in Figure 8. In each case, the HOMO includes a large (~45%)
contribution from the iridium d-orbitals, with only a minor contribution of 2-3% from the N˄N ligands
(either pyridyl-1,2,4-triazole for 8a, 8b and 8d or pyridyl-1,3,4-oxadiazole for 8c). The largest
contribution to the HOMO for these complexes is from the 2-phenylpyridine ligands (~48%). The
LUMO is similar in nature for all four complexes, with the metal only contributing 2-3%, while the

Page 15 of 28
Dalton Transactions
dominant contribution (95-97%) comes from the triazole or oxadiazole N˄N ligands. There is a
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DOI: 10.1039/D0DT02177F
negligible contribution from the boronic acid moiety to either the HOMO or LUMO of all four
complexes.
Figure 8. BP86/def2-TZVP calculated Mulliken populations of the frontier MOs of complexes 8a-
8d.
Time-dependent density-functional theory (TD-DFT) calculations were carried out to elucidate the
nature of the transitions in the absorbance profiles (Table 3). For all complexes, the higher energy
transitions (abs < 300 nm) are identified as predominantly ligand-to-ligand charge transfer (LLCT)
transitions. Transitions occurring within the range 300-360 nm can be predominantly characterised
as metal-to-ligand charge transfer (MLCT) and metal-ligand-to-ligand charge transfer transitions
(MLLCT) associated with excitation from the HOMO. The most intense transitions are typically the
HOMO-LUMO and HOMO-LUMO+1, although here 8c appears to be different with the HOMO-
LUMO oscillator strength being negligible while the HOMO-2 to LUMO transition has appreciable
oscillator strength. These TD-DFT results rationalise the different absorbance spectrum observed for
8c in comparison with the other complexes.

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Table 3. B97XD/def2-TZVP calculated absorbance wavelength (nm), oscillator strength, and
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DOI: 10.1039/D0DT02177F
dominant contribution of the first three transitions of complexes 8a-8d.
Oscillator
Excitation Wavelength
Contributions
Strength
0.079
0.081
0.006
0.038
0.117
0.006
0.003
0.158
0.083
0.056
0.097
0.006
8a
8b
8c
8d
1
2
3
1
2
3
1
2
3
1
2
3
331.88
327.05
320.69
329.48
328.29
319.68
351.49
326.29
318.38
329.20
328.36
319.85
54.0% HOMO  LUMO+1
51.2% HOMO  LUMO
80.1% HOMO  LUMO+2
70.3% HOMO  LUMO
73.6% HOMO  LUMO+1
81.1% HOMO  LUMO+2
77.3% HOMO  LUMO
80.1% HOMO  LUMO+1
44.6% HOMO-2  LUMO
65.1% HOMO  LUMO
66.2% HOMO  LUMO+1
81.6% HOMO  LUMO+2
Conclusion
A modular synthetic procedure has been developed for the generation of bidentate 1,2,4-triazole- and
1,3,4-oxadiazole -based ligands bearing boronic acid groups. The developed synthesis is convergent
and benzhydrazide and pyridine-2-thiocarboxamide precursors substituted with boronic acid groups
protected as pinacol esters were initially prepared. This approach allowed for the introduction of the
boronic acid units at two different positions on the final ligand molecules. The Ir(III) complexes of
the synthesised triazole and oxadiazole ligands were synthesised in a straight forward manner by
reaction of the precursor complex [Ir(ppy)2]2 with the chosen ligand.
This series of Ir(III) complexes were prepared as potential luminescent sensors for carbohyrates as,
although there has been great interest in boronic acid-based carbohydrate probes there remains very
few examples which incorporate inorganic luminophores. Luminescent inorganic molecules offer
several potential advantages over organic probes for biological applications, such as large Stokes
shifts, long luminescent lifetimes and resistance to photobleaching. The luminescent properties of the
prepared complexes were investigated, and the complexes were emissive at ~590 nm. Theoretical
computational studies showed that the HOMO for this series of complexes is primarily centred on the
iridium d-orbitals and 2-phenylpyridine ligands while the LUMO is predominantly on the N˄N
ligands (either pyridyl-1,2,4-triazole or pyridyl-1,3,4-oxadiazole ).

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Dalton Transactions
The capacity of the complexes to form cyclic boronic acid esters with the sugars glucose and fructose
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DOI: 10.1039/D0DT02177F
was evaluated using both high resolution mass spectrometry (in the case of complex 8d) and
luminescence titration studies. The results of these studies show that the complexes displayed
increased levels of cyclic boronic ester formation with fructose when compared to glucose. Higher
binding affinities for fructose compared to glucose for monoboronic acids such as compounds 8a-8d,
has been noted previously and is believed to result from fructose adopting a relatively high
concentration of the β-D-fructofuranose form in solution,39, 40 which contains a pair of hydroxyl
groups that are ideally oriented for boronic acid binding.41 In addition, a clear dependence on solution
pH was seen for sugar-adduct formation, with adducts formed more readily at higher pH (e.g. pH=9).
This finding is likely to result from the boronate anion (formed at higher pH when the Lewis acidic
boronic acid reacts with hydroxide anions) reacting more readily with diols, to form the boronate
cyclic ester.
On the basis of results for previously reported mono-boronic acid sensors, the new Ir(III)-based
complexes described here are not expected to display significant selectivity for other more complex
carbohydrates such as N-acetyl-substituted sugars or glycoproteins/glycolipids. The development of
selective boronic acid-based sensors has been a field of significant interest and a raft of compounds
based on organic luminophores have been evaluated.1 Diboronic acid-based sensors, which provide
a selective recognition site for carbohydrates have received considerable attention. For example
compound 9 was designed based on a rigid scaffold to specifically complex α-D-glucopyranose at
the 1,2 and 4,6 positions.42
B(OH)2
B(OH)2
O
O
CH3
OH
9
Figure 9. Structure of diboronic acid-based sensor (9) designed to specifically complex α-D-
glucopyranose.42
Similar approaches have also been investigated for the selective recognition of more complex
carbohydrates and a diboronic acid-functionalized peptide receptor has been reported for the
recognition of cell surface glycans such as the cancer-associated glycan sialyl Lewis X.43
Although experimental results show that compounds 8a - 8d do form the desired adducts with the
sugars glucose and fructose, only low to moderate levels of photoluminescence quenching were
observed for even the most active complex 8d. These studies suggest that the influence of sugar

Dalton Transactions
Page 18 of 28
binding on luminescence depends on proximity to a frontier orbital. Therefore, we are currently
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DOI: 10.1039/D0DT02177F
developing a new class of sensors where the boronic acid group is placed closer to the metal atom or
located on the 2-phenylpyridine ligands. Incorporation of the boronic acid groups on the 2-
phenylpyridine ligand will allow for Ir(III) complexes to be prepared bearing two boronic acid groups,
so as to provide increased selective recognition for carbohydrates.
Experimental Details
General Procedures
All reagents were purchased from Sigma Aldrich, Alfa Aesar or Precious Metals Online and were
used without further purification. NMR spectra were recorded on either a Bruker Avance ARX-400
1
(400.13 MHz for 1H, 100.61 MHz for 13C), or a Bruker Avance ARX-500 (500.13 MHz for H,
125.77 MHz for 13C) spectrometer and were internally referenced to solvent resonances. High-
resolution mass spectra were obtained using an Agilent 6530 QTOF LC/MS mass spectrometer fitted
with an Agilent electrospray ion (ESI) source. UV-visible spectra were recorded using an Agilent
Technologies Cary 300 UV-visible spectrophotometer using quartz cuvettes (1 cm). Fluorescence
spectra were recorded on a Varian Cary Eclipse spectrofluorimeter (5 nm bandpass, 1 nm data
interval, PMT voltage: 600 V) using quartz cuvettes (1 cm).
X-ray Crystallography
Single crystals of ligand 7c and complexes 8a and 8d suitable for X-ray diffraction studies were
grown by slow evaporation in dichloromethane solutions of these complexes. Crystallographic data
for all structures determined are given in Table S1 (ESI). For all samples, crystals were removed from
the crystallisation vial and immediately coated with Paratone oil on a glass slide. A suitable crystal
was mounted in Paratone oil on a glass fibre and cooled rapidly to 128 K (7c) or 116 K (8a) or 150
K (8d) in a stream of cold N2 using an Oxford low-temperature device. Diffraction data were
measured using an Oxford Gemini diffractometer mounted with Mo-Kα  = 0.71073 Å and Cu-Kα 
= 1.54184 Å. Data were reduced and corrected for absorption using the CrysAlis Pro program.44 The
SHELXL2013-245 program was used to solve the structures with Direct Methods, with refinement by
the Full-Matrix Least-Squares refinement techniques on F2. The non-hydrogen atoms were refined
anisotropically and hydrogen atoms were placed geometrically and refined using the riding model.
Coordinates and anisotropic thermal parameters of all non-hydrogen atoms were refined. All
calculations were carried out using the program Olex2.46 Further XRD details are provided in the
Electronic Supplementary Information. CCDC 2005921-2005923 contains the supplementary
crystallographic data for this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/structures/

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Dalton Transactions
High resolution mass spectrometric sugar-binding studies
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To 1 mL of an aqueous stock solution of complex of 8d (1.48 × 10-4 M) was added D1OIm: 10L.10o3f9/De0itDhTe02r177F
fructose (1.48 × 10-3 M) or 1 mL of glucose (1.48 × 10-3 M) solutions. The pH of the solutions (either
7 or 9) were adjusted by adding aliquots of an aqueous NaOH (0.01 M) solution. Mass spectra were
recorded 3 h after mixing.
Photoluminescence sugar-binding studies
Stock solution of Ir(III) complexes 8a-8d (1 mM) were prepared in methanol and 40 μL of the chosen
stock was diluted with 2 mL of tris buffer (20 mM) and adjusted to either pH 7 or 9, giving a final
complex concentration of 20 μM. The titration was carried out with additions of either fructose or
glucose stock solutions (2 μL, 4 mM) prepared in tris buffer at the appropriate pH. The UV-visible
absorption and luminescence spectra were recorded 10 minutes after mixing. The excitation
wavelength used in the photoluminescence studies was 335 nm.
Computational Methods
DFT calculations were carried out within the Gaussian 16 suite of programs.47 Ground state
geometries were optimized with the mPW1PW91 functional48 in conjunction with the def2-SVP basis
set.49, 50 Stationary points were characterized as minima through analytical frequency calculations at
the same level of theory. All structures are minima with no imaginary frequencies. Molecular orbital
(MO) analysis was performed using the def2-TZVP basis set and core potential,49, 50 combined with
the BP86 functional.51, 52 TD-DFT calculations were performed using the B97XD functional53 and
def2-SVP basis set. All calculations included the use of an implicit solvent model of acetonitrile and
utilized the polarizable continuum model (PCM) self-consistent reaction field (SCRF)54 together with
Truhlar’s SMD solvent model.55
Synthesis
3c. A mixture of 4-aminophenylboronic acid pinacol ester (5 g, 22.8 mmol), sulfur (15 g, 468 mmol)
and Na2S.9H2O (2 g) in 2-methylpyridine (60 mL) was heated at reflux for 24 h. The mixture was
then cooled to RT and the volatiles were evaporated under reduced pressure. The resulting dark brown
liquid was purified on silica with hexane and ethyl acetate 4:1 as the eluent. Compound 3c was
1
obtained as a brown crystalline solid (yield 6.6 g, 85%). H NMR (500 MHz, CDCl3): δ =1.36 (s, 12
H, CH3), 7.48 (t, 3JHH = 6.15 Hz, 1 H, PyH), 7.87-7.92 (m, 3 H), 8.12-8.14 (m, 2 H, PhH), 8.56 (d,
3JHH = 4.69 Hz, 1 H, PyH), 8.80 (d, 3JHH = 8.03 Hz, 1 H, PyH), 12.14 (br. s, 1 H, CSNH) ppm. 13C

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NMR (500 MHz, CDCl3): δ = 25.1 (4-CH3), 84.1 (2 C, Cq), 121.7 (PhC), 125.0 (PyC), 126.3(PyC),
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DOI: 10.1039/D0DT02177F
135.8 (PhC), 137.7 (PyC), 141.4 (PhC), 146.7 (PyC), 151.7 (PyC), 188.0 (CSNH) ppm.
4a. To a solution of NaOEt (prepared by dissolving sodium (0.6 g, 26.2 mmol) in dry ethanol (100
mL) was added compound 3a (3.32 g, 21.81 mmol) and the reaction mixture was stirred at RT for 30
minutes. Bromoethane (2.85 g, 26.17 mmol) was then added to the orange solution, and the reaction
mixture was heated at 50 °C for 24 h during which time a precipitate of NaBr formed. After cooling,
the mixture was filtered through a plug of Celite and the volatiles were evaporated from the filtrate
under reduced pressure. The orange liquid residue was dissolved in dichloromethane (60 mL) and the
mixture was washed with water, brine and finally 1 M Na2CO3 and dried with Na2SO4. Evaporation
of the volatiles under reduced pressure gave 4a as an orange oil (yield 3.33 g, 85%). This material
was unstable and attempts to purify it on silica were unsuccessful and it was utilised in following
reactions without purification or characterisation.
4b. This compound was prepared as described for 4a from NaOEt (prepared by dissolving sodium
(0.59 g, 25.76 mmol) in ethanol (100 mL), 3b (4.6 g, 21.46 mmol) and bromoethane (2.81 g, 25.76
mmol) and was obtained as an orange oil (yield 4.94 g, 95%).
4c. This compound was prepared as described for 4a from NaOEt (prepared by dissolving sodium
(0.07 g, 3.17 mmol) in anhydrous ethanol (30 mL), 3c (0.9 g, 2.65 mmol) and bromoethane (0.35 g,
3.17 mmol) and was obtained as an orange oil (yield 0.94 g, 96%).
5a. A mixture of 4a (0.70 g, 3.88 mmol) and 2a (1.22 g, 4.65 mmol) in 1-butanol (20 mL) was heated
at reflux for 72 h. On cooling, the product crystallized from the reaction mixture. Diethyl ether (10
mL) was added and the solid was collected yielding compound 5a as a colourless solid. (yield 0.60
g, 43%). 1H NMR (500 MHz, CDCl3): δ = 1.38 (s, 12 H, CH3), 4.07 (s, 3 H, CH3),7.36 (t, 3JHH = 6.26
Hz, 1 H, PyH), 7.71-7.73 (m, 2 H, PhH) , 7.85 (t, 3JHH = 7.74 Hz, 1 H, PyH), 7.96-7.98 (m, 2 H, PhH),
8.35 (d, 3JHH = 7.95 Hz, 1 H, PyH), 8.68 (d, 3JHH = 4.84 Hz, 1 H, PyH) ppm. 13C NMR (500 MHz,
CDCl3): δ = 25.11 (4-CH3), 34.5 (CH3), 84.4 (2 C, Cq), 124.2 (PyC), 124.3 (PyC), 128.6 (PhC), 129.8
(PhC), 135.3 (PhC), 137.2 (PyC), 148.3 (PyC), 149.0 (PyC), 153.7 (TzC), 157.0 (TzC) ppm.
5b and 5c. A mixture of 4b (0.92 g, 3.8 mmol) and 2a (0.83 g, 3.17 mmol) in 1-butanol (20 mL) was
heated to reflux for 24 h under an N2 atmosphere. On cooling, the volatiles were evaporated under
reduced pressure, and the crude product was purified on silica with hexane and ethyl acetate (2:3) as
the eluent and two separate compound containing fractions were collected. After removal of the
solvent compounds 5b and 5c were obtained as colourless crystalline solids. (yield 0.24 g, 18%) and
(yield 0.24 g, 22%). 1H NMR (500 MHz, CDCl3): δ = 1.33 (s, 12 H, CH3), 7.20-7.23 (m, 3 H), 7.36-
7.45 (m, 5 H), 7.71-7.72 (m, 2 H, PhH), 7.76 (t, 3JHH = 7.77 Hz, 1 H, PyH), 8.10 (d, 3JHH = 7.85 Hz,

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Dalton Transactions
1 H, PyH), 8.34 (d, 3JHH = 4.23 Hz, 1 H, PyH) ppm. 13C NMR (500 MHz, CDCl3): δ = 25.1 (4-CH3),
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84.2 (2 C, Cq),124.1 (PyC), 124.6 (PyC), 128.2 (PhC), 129.2 (PhC), 129.4 (PhC), 129.5 (PhC), 134.8
(PhC), 136.1 (PhC), ), 136.8 (PhC), 147.3 (PyC), 149.2 (PyC), 154.1 (TzC), 155.7 (TzC) ppm. HRMS
(CH3CN) calcd. for [C50H50B2N8NaO4]+ = 871.4039, found 871.4054.
5c. 1H NMR (500 MHz, CDCl3): δ = 1.37 (s., 12 H, CH3), 7.48 (t, 3JHH = 5.95 Hz, 1 H, PyH), 7.91 (t,
3JHH = 7.66 Hz, 1 H, PyH), 7.96-7.97 (m, 2 H, PhH), 8.21-8.23 (m, 2 H, PhH), 8.33 (d, 3JHH = 7.85
Hz, 1 H, PyH), 8.83 (d, 3JHH = 4.72 Hz, 1 H, PyH) ppm. 13C NMR (500 MHz, CDCl3): δ = 24.9 (4-
CH3), 84.3 (2 C, Cq), 123.3 (PyC), 125.7 (PyC), 125.8 (PhC), 126.4 (PhC), 135.3 (PhC), 137.2 (PyC),
143.6 (PyC), 150.4 (PyC), 164.0 (TzC), 165.6 (TzC) ppm. HRMS (CH3CN) calcd. for
[C38H40B2N6NaO6]+ = 721.3093, found 721.3120.
5d. This compound was prepared as described for 5a from 4c (0.94 g, 2.55 mmol) and 2b (0.42 g,
3.06 mmol). After removal of the volatiles under reduced pressure the orange liquid was suspended
in isopropanol and a precipitate formed which was collected and washed with diethyl ether.
Compound 5d was obtained as a colourless solid. (yield 0.50 g, 46%). 1H NMR (500 MHz, CDCl3):
δ = 1.36 (s., 12 H, CH3), 7.19-7.23 (m, 3 H), 7.27-7.30 (m, 2 H, PhH), 7.35 (t, 3JHH = 7.44 Hz, 1 H,
PyH), 7.42-7.44 (m, 2 H, PhH), 7.75 (t, 3JHH = 7.80 Hz, 1 H, PyH), 7.79-7.80 (m, 2 H, PhH), 8.08 (d,
3JHH = 7.91 Hz, 1 H, PyH), 8.34 (d, 3JHH = 4.83 Hz, 1 H, PyH) ppm. 13C NMR (500 MHz, CDCl3): δ
= 25.1 (4-CH3), 84.5 (2 C, Cq),124.0 (PyC), 124.5 (PyC), 127.0 (PhC), 127.5 (PhC), 128.6 (PhC),
129.1 (PhC), 129.9 (PhC), 135.7 (PhC), 136.8 (PhC), 138.5 (PyC), 147.2 (PyC), 149.2 (PyC), 153.9
(TzC), 155.7 (TzC) ppm.
6a. To a solution of 5a (0.20 g, 0.55 mmol) in methanol (3 mL) was added aqueous KHF2 (0.70 mL,
4.5 M, 3.12 mmol) and the resulting white slurry was stirred at RT for 30 minutes. The volatiles were
then removed under reduced pressure yielding a solid that was recrystallised from acetonitrile,
yielding 6a as a white crystalline solid. (yield 0.14 g, 74%). 1H NMR (500 MHz, DMSO): δ = 3.97
(s, 3 H, CH3), 7.47-7.54 (m, 5 H), 8.00 (t, 3JHH = 7.61 Hz, 1 H, PyH), 8.17 (d, 3JHH = 7.89 Hz, 1 H,
PyH), 8.74 (d, 3JHH = 4.23 Hz, 1 H, PyH) ppm. 13C NMR (400 MHz, DMSO): δ = 33.8 (CH3), 123.4
(PyC), 123.6 (PhC), 124.2 (PhC), 127.0 (PhC), 131.6 (PyC), 137.5 (PyC), 147.9 (PyC), 149.1 (PyC),
152.5 (TzC), 157.1 (TzC) ppm.
6b. A suspension of 5b (0.17 g, 0.4 mmol) in methanol (5 mL) was heated at reflux for 30 minutes,
yielding a yellow solution. A hot aqueous solution of KHF2 (0.49 mL, 4.5 M, 2.20 mmol) was added
and the resulting mixture was stirred for 30 minutes at reflux during which time a precipitate formed.
The precipitated solid was collected and washed with diethyl ether yielding 6b as a white solid. (yield
0.13 g, 80%). 1H-NMR (400 MHz, DMSO): δ = 7.10-7.11 (m, 2 H, PhH), 7.24 (d, 3JHH = 7.80 Hz, 1

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H, PyH), 7.28-7.29 (m, 2 H, PhH),7.36-7.41 (m, 5H), 7.90 (t, 3JHH = 7.96 Hz, 1 H, PyH), 7.97 (d, 3JHH
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13
DOI: 10.1039/D0DT02177F
= 7.90 Hz, 1 H, PyH), 8.34 (d, JHH = 4.23 Hz, 1 H, PyH) ppm. C NMR (400 MHz, DMSO): δ
=123.2 (PyC), 124.6 (PhC), 126.8 (PhC), 127.1 (PhC), 128.6 (PhC), 129.5 (PhC), 131.6 (PhC), 131.6
(PhC), 132.2 (PyC), 137.0 (PyC), 147.0 (PyC), 149.3 (PyC), 154.0 (TzC), 154.7 (TzC) ppm.
6c. This compound was prepared as described for 6a from 5c (0.1 g, 0.30 mmol) and aqueous KHF2
(0.362 mL, 4.5 M, 1.63 mmol) and after recrystallization from acetonitrile gave 6c as a white
crystalline solid. (yield 0.076 g, 77%). 1H NMR (500 MHz, DMSO): δ = 7.56-7.57 (m, 2 H, PhH),
7.64 (t, 3JHH = 6.21 Hz, 1 H, PyH), 7.86-7.87 (m, 2 H, PhH), 8.07 (t, 3JHH = 7.76 Hz, 1 H, PyH), 8.25
(d, 3JHH = 7.88 Hz, 1 H, PyH), 8.81 (d, 3JHH = 4.79 Hz, 1 H, PyH) ppm. 13C NMR (400 MHz, DMSO):
δ = 119.9 (PhC), 122.9 (PyC), 124.8 (PhC), 126.2 (PyC), 132.2 (PhC), 137.8 (PyC), 143.0 (PyC),
150.3 (PyC), 163.1 (TzC), 165.7 (TzC) ppm.
6d. This compound was prepared as described for 6b from 5d (0.42 g, 0.99 mmol) and aqueous KHF2
(1.25 mL, 4.5 M, 5.63 mmol) and was obtained 6d as a white crystalline solid. (yield 0.38 g, 95%).
1H-NMR (400 MHz, DMSO): δ = 6.99-7.01 (m, 2 H, PhH), 7.29-7.31 (m, 2 H, PhH), 7.33-7.40 (m,
5 H), 7.83 (d,3JHH = 7.81 Hz, 1 H, PhH), 7.88 (t, 3JHH = 7.78 Hz, 1 H, PyH), 8.45 (d, 3JHH = 4.40 Hz,
1 H, PyH) ppm. 13C NMR (400 MHz, DMSO): δ =124.2 (PyC), 124.4 (PhC), 125.6 (PhC), 127.2
(PhC), 128.4 (PhC), 129.5 (PhC), 131.9 (PhC), 131.9 (PhC), 132.1 (PyC), 136.9 (PyC), 146.9 (PyC),
149.2 (PyC), 153.9 (TzC), 154.7 (TzC) ppm.
7a. A mixture of 6a (0.12 g, 0.35 mmol) and LiOH (0.12 g, 0.35 mmol) in water (3 mL) and
acetonitrile (4 mL) was stirred at RT for 24 h and was then acidified to pH 1-2 with saturated NH4Cl
(4 mL) and 1 M hydrochloric acid (2 mL). The white precipitate was collected and recrystalised from
hot acetonitrile, yielding 7a as a white crystalline solid. (yield 0.058 g, 59%). 1H NMR (500 MHz,
DMSO): δ = 4.00 (s, 3 H, CH3), 7.54 (t, 3JHH=6.13 Hz,1 H, PyH), 7.73-7.75 (m, 2 H, PhH), 7.96-7.98
3
3
(m, 2 H, PhH), 8.02 (t, JHH =7.86 Hz, 1 H, PyH), 8.19 (d, JHH=7.94 Hz, 1 H, PyH), 8.25 (s, 2 H
3
B(OH)2), 8.75 (d, JHH =4.19 Hz, 1 H, PyH) ppm. 13C NMR (500 MHz, DMSO): δ = 34.4 (CH3),
124.0 (PyC), 124.8 (PyC), 128.3 (PhC), 128.8 (PhC), 134.9 (PhC), 135.6 (PhC), 138.0 (PyC), 148.1
(PyC), 149.6 (PyC), 153.3 (TzC), 156.6 (TzC) ppm. HRMS (CH3OH) calcd. for [C15H16BN4O2]+ =
295.1366, found 295.1367; calcd. for [C15H15BN4NaO2]+ = 317.1186, found 317.1191.
7b. This compound was prepared as described for 7a from 6b (0.11 g, 0.26 mmol) and LiOH (0.038
g, 0.91 mmol). (yield 0.058 g, 65%). 1H-NMR (400 MHz, DMSO): 7.34-7.44 (m, 8 H), 7.71-7.73 (m,
2 H, PhH), 7.92 (t, 3JHH= 7.98 Hz, 1 H, PyH), 8.01 (d, 7.84 Hz, 1 H, PyH), 8.15 (s, 2 H B(OH)2), 8.35
(d, 4.40 Hz, 1 H, PyH). 13C-NMR: (400 MHz, DMSO): δ = 124.2 (PyC), 124.3 (PyC), 127.5 (PhC),
128.2 (PhC), 128.2 (PhC), 129.1 (PhC), 129.1 (PhC), 133.9 (PhC), 135.4 (PyC), 137.1 (PhC), 146.6

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(PyC), 149.0 (PyC), 153.4 (TzC), 154.9 (TzC) ppm. HRMS (CH3OH) calcd. for [C20H18BN4O2]+ =
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+
DOI: 10.1039/D0DT02177F
357.1523, found 357.1534; calcd. for [C20H17BN4NaO2] = 379.1342, found 379.1354.
7c. This compound was prepared as described for 7a from 6c (0.059 g, 0.18 mmol) and LiOH (0.03
3
g, 0.63 mmol). (yield 0.025 g, 52%). 1H NMR (500 MHz, DMSO): δ = 7.67 (t, JHH=6.15 Hz,1 H,
PyH), 8.01-8.03 (m, 2 H, PhH), 8.07-8.10 (m, 3 H), 8.28 (d, 3JHH =7.83 Hz, 1 H, PyH), 8.33 (s, 2 H
3
B(OH)2), 8.25 (d, JHH =4.70 Hz, 1 H, PyH) ppm. 13C NMR (500 MHz, DMSO): δ = 123.6 (PyC),
124.9 (PyC), 126.1 (PhC), 127.0 (PhC), 135.4 (PhC), 138.4 (PyC), 138.4 (PhC), 143.3 (PyC), 151.0
(PyC), 164.1 (TzC), 165.3 (TzC) ppm. HRMS (CH3OH) calcd. for [C14H13BN3O3] + = 282.1050,
found 282.1047; calcd. for [C14H12BN3NaO3]+ = 304.0869, found 304.0874
7d. This compound was prepared as described for 7a from 6d (0.1 g, 0.25 mmol) and LiOH (0.036
g, 0.87 mmol). (yield 0.04 g, 47%). 1H-NMR (400 MHz, DMSO): 7.27-7.29 (m, 2 H, PhH),7.33-7.40
(m, 6 H), 7.75-7.77 (m, 2 H, PhH), 7.92 (t,3JHH =7.73 Hz, 1 H, PyH), 7.99 (d, 7.80 Hz, 1 H, PyH),
8.30 (s, 2 H B(OH)2), 8.35 (d, 4.75 Hz, 1 H, PyH). 13C-NMR: (400 MHz, DMSO): δ = 124.2 (PyC),
124.3 (PyC), 126.9 (PhC), 127.0 (PhC), 128.5 (PhC), 128.6 (PhC), 129.7 (PhC), 134.8 (PhC), 136.8
(PhC), 137.1 (PyC), 146.6 (PyC), 149.0 (PyC), 153.4 (TzC), 154.8 (TzC) ppm. HRMS (CH3OH)
calcd. for [C20H18BN4O2]+ = 357.1523, found 357.1466; calcd. for [C20H17BN4NaO2]+ = 379.1342,
found 379.1276.
8a. To a solution of [Ir(ppy)2]2 (0.11 g, 0.1 mmol) in dichloromethane (15 mL) and ethanol (5 mL)
was added 7a (56 mg, 0.2 mmol) and the mixture was stirred under an atmosphere of N2 for 24 h.
The volatiles were then removed under reduced pressure and the crude product was purified on silica
with dichloromethane and methanol 4:1 as the eluent, yielding complex 8a was obtained as a yellow
crystalline solid. (yield 0.07 g, 43%). 1H-NMR (500 MHz, DMSO): δ= 4.19 (s, 3 H, CH3), 6.12 (d,
3JHH= 7.45 Hz, 1 H), 6.15 (d, 3JHH= 7.45 Hz, 1 H), 6.77 (t, 3JHH= 7.01 Hz, 1 H), 6.89 (t, 3JHH= 7.47
Hz, 1 H), 7.01 (t, 3JHH= 7.78 Hz, 1 H), 7.19-7.25 (m, 2 H), 7.58 (d, 3JHH= 5.47 Hz, 1 H), 7.63-7.65(m,
3
3
3
2 H), 7.72 (t, JHH= 5.72 Hz, 1 H), 7.80 (d, JHH= 7.60 Hz, 1 H), 7.88-7.98 (m, 7 H), 8.23 (t, JHH=
7.56 Hz, 2 H), 8.29 (t, 3JHH= 7.40 Hz, 2 H), 8.40 (s, 2 H, B(OH)2), 8.61 (d, 3JHH= 8.19 Hz, 1 H) ppm.
13C-NMR (500 MHz, DMSO): δ = 79.7, 119.5, 119.7, 120.0, 120.2, 122.0, 122.8, 124.0, 124.3, 124.8,
124.9, 125.0, 125.4, 125.5, 125.6, 126.3, 129.0, 130.5, 131.5, 135.0, 138.8, 139.0, 140.4, 144.2, 144.7,
145.6, 148.0, 149.6, 150.6, 151.4, 156.9, 158.5, 167.3, 167.7 ppm. HRMS (CH3CN) calcd. for
[C36H29BIrN6O2]+ = 781.2074, found 781.2083.
8b. This compound was prepared as described for 8a from [Ir(ppy)2]2 (0.072 g, 0.067 mmol) and 7b
(0.046 g, 0.134 mmol). The crude product was purified by the diffusion of vapours between an
acetonitrile solution of the crude product and diethyl ether, yielding complex 8b as a yellow

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3
crystalline solid. (yield 0.03 g, 25%). 1H-NMR (500 MHz, DMSO): δ= 6.13 (d, JHH = 7.56, 1 H),
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6.19 (d, 3JHH = 7.59 Hz, 1 H), 6.80 – 6.83 (m, 2 H), 6.88-6.95 (m, 2 H), 7.01 (t, 3JHH = 7.48 Hz, 1 H),
DOI: 10.1039/D0DT02177F
7.25 (t, 3JHH = 6.60 Hz, 1 H), 7.30 – 7.34 (m, 3 H), 7.62 (t, 3JHH = 6.15 Hz, 1 H), 7.69-7.79 (m, 6 H),
7.84-7.92 (m, 5 H), 7.96-8.02 (m, 3 H), 8.11 (d,3JHH = 5.80, 2 H), 8.24-8.26 (m, 1 H), 8.25 (s, 2 H
13
B(OH)2) ppm. C-NMR: (400 MHz, DMSO): δ =119.7, 119.8, 121.7, 122.4, 123.1, 123.8, 124.1,
124.5, 124.6, 125.0, 127.3, 128.7, 128.9, 129.0, 129.4, 130.2, 131.0, 131.0, 131.2, 134.2, 136.3, 138.5,
138.7, 139.8, 143.9, 144.3, 144.4, 147.2, 149.6, 150.3, 150.4, 151.1, 155.7, 156.8, 166.7, 167.2 ppm.
HRMS (CH3CN) calcd. for [C41H31BIrN6O2]+ = 843.2231, found 843.2249.
8c. This compound was prepared as described for 8a from [Ir(ppy)2]2 (0.10 g, 0.095 mmol) and 7c
(0.051 g, 0.19 mmol). The dark orange crude product was recrystallized from acetonitrile, yielding
complex 8c as an orange crystalline solid. (yield 0.13 g, 85%). 1H-NMR (500 MHz, DMSO): δ= 6.12
(t, 3JHH = 9.60, 2 H), 6.83 (t, 3JHH = 7.42 Hz, 1 H), 6.91 (t, 3JHH = 7.42 Hz, 1 H), 6.96 (t, 3JHH = 7.42
Hz, 1 H), 7.02 (t, 3JHH = 7.58 Hz, 1 H), 7.17 – 7.21 (m, 2 H), 7.65 (d, 3JHH = 5.30, 1 H), 7.82-7.86 (m,
3
3 H), 7.89 (d, JHH = 7.60 Hz, 1 H), 7.95 (t, 3JHH = 7.90 Hz, 2 H), 8.01 (d,3JHH = 8.16, 2 H), 8.10
(d,3JHH = 8.24, 2 H), 8.24 (d,3JHH = 8.20, 2 H), 8.27 (d,3JHH = 5.66, 1 H), 8.38-8.41 (m, 1 H), 8.39 (s,
2H B(OH)2), 8.70 (d,3JHH = 7.91, 1 H) ppm. 13C-NMR: (400 MHz, DMSO): δ = 119.6, 119.8, 122.1,
122.7, 123.2, 123.7, 123.9, 124.6, 125.0, 125.9, 126.2, 129.5, 130.2, 130.8, 131.3, 135.0, 138.7, 138.9,
140.5, 141.1, 144.1, 144.2, 144.8, 147.3, 150.2, 150.8, 151.3, 166.2, 166.8, 166.9, 168.4 ppm. HRMS
(CH3CN) calcd. for [C35H26BIrN5O3]+ = 768.1758, found 768.1771.
8d. This compound was prepared as described for 8a from [Ir(ppy)2]2 (0.084 g, 0.079 mmol) and 7d
(0.054 g, 0.16 mmol). The yellow crude product was recrystallized from acetonitrile, yielding
complex 8d as a yellow crystalline solid. (yield 0.11 g, 79%). 1H-NMR (500 MHz, DMSO): 1H-NMR
(500 MHz, DMSO): δ= 6.14 (d, 3JHH = 3.62, 1 H), 6.19 (d, 3JHH = 3.62 Hz, 1 H), 6.79 – 6.85 (m, 2
H), 6.88-6.94 (m, 2 H), 7.01 (t, 3JHH = 7.43 Hz, 1 H), 7.25 (t, 3JHH = 6.54 Hz, 1 H), 7.30 – 7.39 (m, 5
H), 7.44 (t, 3JHH = 7.06 Hz, 1 H), 7.62 (t, 3JHH = 6.45 Hz, 1 H), 7.72 (d, 3JHH = 5.76, 1 H), 7.81 – 7.90
(m, 5 H), 7.96 – 8.01 (m, 3 H), 8.09 – 8.13 (m, 3 H), 8.25 (d,3JHH = 4.23, 2 H), 8.46 (s, 2 H B(OH)2)
13
ppm. C-NMR: (400 MHz, DMSO): δ = 119.7, 119.8, 121.7, 122.4, 123.0, 123.8, 124.0, 124.5,
124.6, 125.0, 127.3, 128.7, 128.9, 129.0, 129.4, 130.2, 131.0, 131.0, 131.2, 134.2, 136.3, 138.5, 138.7,
139.8, 143.9, 144.3, 144.4, 147.2, 149.6, 150.3, 150.4, 151.1, 155.7, 156.8, 166.7, 167.2 ppm. HRMS
(CH3CN) calcd. for [C41H31BIrN6O2]+ = 843.2231, found 843.2245.
Conflict of Interests
There are no conflicts of interest to declare.
Acknowledgements

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We acknowledge generous allocating of computing resources by NCI, Intersect, and La Trobe
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DOI: 10.1039/D0DT02177F
University.
Electronic Supplementary Information (ESI)
Synthetic description for compounds 1a, 1b, 2a, 2b, 3a and 3b, further X-ray diffraction details, mass
spectra for compounds 5b, 5c, 7a, 7b, 7c, 7d, 8a, 8b, 8c and 8d and luminescence titration results for
compounds 8a, 8b and 8c.
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