Control of On-Off or Off-On fluorescent and optical [Cu2+] and [Hg2+] responses via formal Me/H substitution in fully characterized thienyl "scorpionate"-like BODIPY systems

Article abstract of DOI:10.1021/ic101681h

One 8-phenyl and two 8-mesityl-substituted "scorpionate"-like BODIPY-type species of the formula [3,4,4-tris(5-R-(2-thienyl))-8-(2,4,6- R′-phenyl)-4-bora-3a,4a-diaza-s-indacene (R = H, R′ = H, 3a; R, = H, R′ = Me, 2a; R, = Me, R′ = Me, 2b)] have been synt

Full text of DOI:10.1021/ic101681h

ARTICLE
pubs.acs.org/IC
Control of OnꢀOff or OffꢀOn Fluorescent and Optical [Cu2þ] and
[Hg2þ] Responses via Formal Me/H Substitution in Fully Characterized
Thienyl “Scorpionate”-like BODIPY Systems
Kibong Kim,†,‡ Shin Hei Choi,†,‡ June Jeon,†,‡ Hyosun Lee,§ Jung Oh Huh,‡ Jaeduk Yoo,|| Jong Taek Kim,‡
Chang-Hee Lee,|| Yoon Sup Lee,‡ and David G. Churchill*,†,‡
†Molecular Logic Gate Laboratory and ‡Department of Chemistry and School of Molecular Science, Korea Advanced Institute of Science
and Technology (KAIST), 373-1 Guseong-dong, Yuseong-gu, Daejeon, 305-701, Republic of Korea
§Organometallic Chemistry Laboratory, Department of Chemistry (BK 21), Kyungpook National University, Daegu 702-701,
Republic of Korea
Department of Chemistry, Kangwon National University, Chun-Chon 200-701, Republic of Korea
S Supporting Information
b
ABSTRACT: One 8-phenyl and two 8-mesityl-substituted
“scorpionate”-like BODIPY-type species of the formula [3,4,
4-tris(5-R-(2-thienyl))-8-(2,4,6-R0-phenyl)-4-bora-3a,4a-diaza-s-
indacene (R = H, R0 = H, 3a; R, = H, R0 = Me, 2a; R, = Me, R0 =
Me, 2b)] have been synthesized and fully characterized.
Importantly, differences in their solution (MeCN) optical Cu2þ
and Hg2þ probing capacity via SSS-chelation were investigated. Compounds 2aꢀ3a were prepared from the requisite 8-substituted
1
BODIPY complexes. They were characterized first by complete H, 11B and 13C NMR spectroscopic assignments (CD3Cl or
CD3C(O)CD3); the molecular structures of 2a and 3a were determined by X-ray crystallography. Compounds 2aꢀ3a were studied
by UVꢀvis and fluorescence spectroscopy [ΦF = 0.27 ( 0.013 (2a); 0.024 ( 0.0016 (2b); 0.0034 ( 0.00047 (3a)]. Importantly,
low [Cu2þ] with 3a (<3.0 ꢁ 10ꢀ5 M) gave rise to an increase of fluorescence intensity (offꢀon; 6.3-fold), whereas with 2a it
decreased (onꢀoff). When [Hg2þ] (<3.0 ꢁ 10ꢀ5 M) was added to 2b, the λem,max value increased (offꢀon; 3.2-fold), and for 2a, it
decreased (onꢀoff). The association constant (Ka) for Hg2þ 2a was determined to be 3120 ( 307 Mꢀ1. An approximate
3
stoichiometric 1:1 binding determined by Job plot analysis is in line with successful DFT modeling of SSS-Cu2þ binding for this
system type. 1H NMR spectroscopy also revealed tentative sets of product complex peaks. These simple differences caused by formal
ligand Me-group incorporation are the first for any related fluorophores, to the best of our knowledge.
’ INTRODUCTION
for optical Cu2þ sensing/detection5ꢀ8 underscore the degree to
which synthetic chemistry holds a command over future syn-
thetic receptor designs, so to offer more options in offꢀon
optical signaling.
Clearly, many challenges still remain in achieving optimal
selectivity and “turn-on” behavior. Separately, Hg2þ sensing is
interesting in environmental chemistry.9ꢀ11 Molecular and ionic
recognition involving “turn-on” fluorescence intensity with Hg2þ
is also challenging because of its quenching nature.
Fluorescence is a sensitive technique. It often relates to various
soluble organic-based molecules that are planar, rigid, and
π-delocalized and is even scalable to where the emissions of single
molecules can be detected. BODIPY-type systems (Figure 1) are
common fluorophore derivatives that continue to be explored
actively.12,13 Thus, further development can be thought of in
terms of imparting by derivatization a variety of features (photo-
physical, solubility, functional groups) advantageous in biotechnology
Selective molecular sensing of metal ions continues to be a
practical research aim in both biological and environmental
chemistry. Deviations from proper metal ion regulation
(normal concentration ranges of, e.g., Cu2þ, Zn2þ, and Fenþ
)
in biological systems may lead to, or signal, disease. Heavy metals
such as Hg2þ and Pb2þ are also important sensing targets
because, while they occur naturally, certain species continue to
persist in the environment as contaminants that stem from
anthropogenic root causes; they are of grave concern if they
are present in the body at high concentrations. Cupric ion
sensing has been a recent research aim for chemists and other
researchers and is considered important because of the correla-
tions Cu2þ concentrations have with distinct changes in biolog-
ical systems (especially neurological systems) and in resulting
pathology. In particular, Cu2þ concentration is thought to be an
important standard, or causative agent, in protein misfolding and
in several neurodegenerative diseases.1ꢀ4 While achieving such
detection adequately is marked by challenges (Cu2þ being a
“universal” fluorescence quencher), recent and leading references
Received: August 18, 2010
Published: May 20, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ic101681h Inorg. Chem. 2011, 50, 5351–5360
|

Inorganic Chemistry
ARTICLE
“scorpionate”-like BODIPY species that are 8-mesityl/phenyl-
substituted [3,4,4-tris(5-R-(2-thienyl))-8-(2,4,6-R0-phenyl)-4-
bora-3a,4a-diaza-s-indacene (R, R0= H, 3a; R = H, R0 = Me, 2a;
R = R0 = Me, 2b)]. This was studied in the context of exploring
new small molecule possibilities in metal ion recognition.
2. EXPERIMENTAL METHODS
General Considerations. All solvents and chemicals used in the
following synthetic steps were of analytical grade and used as received
from reliable commercial sources. The reagents 2-thienyllithium, THF,
2-methylthiophene, and n-butyllithium in THF solution were pur-
chased from Aldrich Chemical Co.; methanol was purchased from
Merck Chemical Co. Compounds 2 and 3 have been reported
previously.32 The synthetic details for the preparation of 2 and 3 were
followed herein. Compound 1 was prepared by us but is also accessible
via the facile coupling route reported by Pe~na-Cabrera et al.34 All
solvents used for NMR spectral analysis were purchased commercially
and were of spectroscopic grade. UVꢀvis absorption and emission
spectra are obtained using a CARY 300 Bio UVꢀvis spectrometer and
a Shimadzu RF-5301 PC spectrophotometer, respectively. Emission
spectra were acquired through the excitation at the λabs,max value, as
assigned in the UVꢀvis absorption spectra for each compound.
Fluorescein in 0.1 N NaOH (ΦF = 0.92)36 was used as the standard
for the fluorescence quantum yield (ΦF) measurements. C, H, and N
elemental analyses were measured for 2a, 2b, and 3a using a Vario EL
III CHNS elemental analyzer. High-resolution MALDI mass spec-
trometry was performed on a Bruker Autoflex III with a Nd YAG laser
source (355 nm) by the research support staff at KAIST (Daejeon,
South Korea) for 2a, 2b, and 3a. HRMS was performed with a Bruker
micrOTOF II mass spectrometer. 1H, 13C, and 11B NMR spectra were
obtained on a Bruker Avance 300 or 400 MHz spectrometer. Spectral
signals were calibrated by the protio impurity of the deuterated solvent.
Tetramethylsilane (Si(CH3)4) was used as an internal NMR spectral
standard.
Figure 1. Some common types of BODIPY derivatives: (a) plain
BODIPY30 with (i) dipyrrin numbering and (ii) indacene numbering
(numbering used in the text); (b) difluoroboryl-1,3,5,7-tetramethyldipyrrin;
(c) difluoroboryl(8-phenyl)- or -8-(2-thienyl)dipyrrin; (d) “scorpionate-
like” BODIPY-type species.
(e.g., bioprobing). BODIPY-type systems have previously ad-
dressed copper cation14ꢀ20 and Hg2þ detection.21ꢀ29
The “scorpionate-like” design involves the BODIPY fluoro-
genic core in which there has been substitution of the fluoride
groups by aryl groups (Figure 1d). The substitution of aryl
groups in place of the two 4-boron position fluorides was first
reported by Ziessel et al., and these groups extend to phenyls,
thiophenes, and larger aromatic systems.12,18,31 We have been
involved with the synthesis and characterization of 2- and
3-thienyl-containing di- and polypyrrolic species in trying to
uncover versatile and robust low molecular weight (MW) multi-
functional probe precursors, preferably related to molecular
neurodegeneration applications. We have previously prepared a
system that exhibited discrete sensing responses to Cu2þ and
Hg2þ in solution.18 Our recent reports with BODIPY-based
chromophores, in terms of Mnþ sensing, have involved a novel
SSS “scorpionate-like” binding cavity (Figure 1d). These reports
raise the question of whether the [N2BAr2] unit is satisfactory
because it results in a derivative with a lowered fluorescence
quantum yield (ΦF).32
Our original interest in simple 8-substituted species derives
from a report by Holten and co-workers,32 in which it was found
that the simple formal replacement of [H] with one methyl
substituent at the “tail” phenyl (o-tolyl) gives a dramatic increase
in ΦF. A related report comes from Sun et al., who reported a
BODIPY species in which the 8-position was a 2-hydroxy-5-
methoxyphenyl group. This group undergoes selective oxidation
with hypochlorous acid to afford a 2,5-quinonyl moiety, where-
upon a “turn-on” green fluorescence response is observed from
the molecule.33 Also, BODIPY species in which oxidation of a
thienyl substituent at the 8-position has also been reported.31 In
terms of thienyl derivatization, there are now new ways to
functionalize the BODIPY core with such heterocycles. Namely,
facile and high-yielding access to the thienyl 8-substitution is
available via coupling chemistry at the 8-position of the 8-sub-
stituted [ꢀSMe] derivative, as reported recently by Pe~na-Cab-
rera and co-workers.34 In the present report, we consider the
BODIPY receptor “head” position bearing thienyl motifs and the
[SSS] core with a phenyl-based meso 8-position “tail” removing
possible ambiguity resulting from Mnþ binding capability of the
“tail” S-donor atom which was present in earlier systems.18,31,35
The substitution pattern in the present system allows for the
quantification of the [CH3] substitution effect, in terms of metal
ion [onꢀoff] and [offꢀon] sensing behavior differences. Herein,
we discuss the synthesis, detailed multinuclear NMR character-
ization, optical properties, and structural aspects of three new
Synthesis of Compound 2a [3,4,4-Tri(2-thienyl)-8-(2,4,6-trimethyl-
phenyl)-4-bora-3a,4a-diaza-s-indacene]. Compound 2 was prepared
by us through a literature method.37 Compound 2 (0.30 g, 0.97 mmol)
was dissolved in anhydrous THF (20 mL) and stirred at ꢀ78 °C for
10 min. Into this solution, a sample of 2-thienyllithium was slowly added
(2.6 mL, 1.0 M in THF). Generally, the synthetic procedure for
compound 2a was similar to that for 1a.18 Finally, compound 2a was
isolated via recrystallization in methanol (0.20 g, 39%). 1H NMR
spectral signals (CD3C(O)CD3: δ 2.05, 400 MHz): δ 7.57 (t, 3JHꢀH
=
3
1.5, 1Hh), 7.40 (dd, JHꢀH = 5.1 Hz, 3JHꢀH = 3.8 Hz, 1Hj), 7.31 (dd,
3JHꢀH = 3.8 Hz, 3JHꢀH = 1.0 Hz, 2Hm), 7.12 (dd, 3JHꢀH = 3.4 Hz, 4JHꢀH
1.0 Hz, 2Hl), 7.06 (s, 2Hb), 6.95 (dd, 3JHꢀH = 4.8 Hz, 4JHꢀH = 1.5 Hz,
=
2Hn), 6.93 (dd, 3JHꢀH = 3.5 Hz, 4JHꢀH = 1.1 Hz, 1Hk), 6.86 (d, 3JHꢀH
=
4.4 Hz, 1He), 6.83 (d, 3JHꢀH = 4.4 Hz, 1Hd), 6.76 (dd, 3JHꢀH = 5.1 Hz,
4JHꢀH = 1.1 Hz, 1Hi), 6.56 (dd, 3JHꢀH = 4.26 Hz, 4JHꢀH = 1.2 Hz, 1Hf),
6.44 (dd, 3JHꢀH = 4.26 Hz, 3JHꢀH = 1.85 Hz, 1Hg), 2.37 (s, 3Hc ), 2.14 (s,
0
6Ha ). 13C NMR spectral signals (CD3C(O)CD3: δ 30.0, 100 MHz): δ
0
152.8 (m, 1C5), 145.4 (s, 1C2), 145.1 (dt, 1JCꢀH = 183.7 Hz, 2JCꢀH = 9.0
Hz, 1Ch), 139.4 (m [looks like: q, 2JCꢀH = 6.0 Hz], 1Cc), 137.7 (m, [looks
like: t, 2JCꢀH = 8.7 Hz] 1C3), 137.1 (m, 2Ca), 134.9 (m, 1C6), 133.9 (m
[looks like: q, 2JCꢀH = 8.6 Hz], 1C4), 132.5 (dm, 1JCꢀH = 155.2 Hz, 1Ck),
131.6 (m, 1C1), 131.0 (dm, 1JCꢀH = 146.2 Hz, 2Cl), 129.9 (dm, 1JCꢀH
203.7 Hz, 1Cj), 129.8 (dm, 1JCꢀH = 170.8 Hz, 1Cd), 129.0 (dm, 1JCꢀH
130.6 Hz, 2Cb), 128.1 (dm, 1JCꢀH = 161.9 Hz, 1Ci), 128.0 (dm, 1JCꢀH
=
=
=
172.7 Hz, 2Cn), 127.4 (dm, 1JCꢀH = 164.6 Hz, 2Cm), 127.2 (dm, 1JCꢀH
= 175.0 Hz, 1Cf), 122.7 (dd, 1JC-H = 174.1 Hz, 2JCꢀH = 3.9 Hz, 1Ce),
119.2 (ddd, 1JCꢀH = 174.1 Hz, 2JCꢀH = 8.6 Hz, 2JCꢀH = 3.1 Hz, 1Cg), 21.2
1
(q, 1JCꢀH = 125.9 Hz, 3JCꢀH = 5.3 Hz, 1Cc ), 20.0 (q, JCꢀH = 125.9 Hz,
0
JC-H = 4.9 Hz, 2Ca ). 11B NMR spectral signals (CD3COCD3, BF3OEt2:
3
0
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dx.doi.org/10.1021/ic101681h |Inorg. Chem. 2011, 50, 5351–5360

Inorganic Chemistry
ARTICLE
δ 0.00, 128 MHz): δ ꢀ2.00 (s), MALDI-TOF m/z (Mþ): 520.13 (calcd)
520.64 (obsd). HRMS m/z ((M þ Na)þ): 543.117 (calcd) 543.117
(obsd). Anal. Calcd for C30H25BN2S3: C, 69.22; H, 4.84; N, 5.38. Found: C,
69.92; H, 4.79; N, 5.19.
signals (CD3COCD3, BF3OEt2: δ 0.00, 128 MHz): δ ꢀ1.99 (s). HRMS
m/z ((M þ Na)þ): 501.070 (calcd), 501.067 (obsd). Anal. Calcd for
C27H19BN2S3: C, 67.78; H, 4.00; N, 5.85. Found: C, 66.63; H, 4.13;
N, 5.64.
Synthesis of 2b [3,4,4-Tri(5-R-(2-thienyl))-8-(2,4,6-R0-phenyl)-4-
bora-3a,4a-diaza-s-indacene (R = R0 = Me)]. The synthesis of com-
pound 2b was similar to that for compound 2a. First, 2-methylthienyl-
lithium was prepared separately. 2-Methylthiophene (0.63 mL, 6.4
mmol) was dissolved in anhydrous THF (10 mL) before being allowed
to undergo reaction with n-BuLi (2.6 mL, 2.5 M in THF) at ꢀ78 °C for
10 min. The reaction mixture was then allowed to warm to ambient
temperature.38 After this procedure, this THF solution was transferred
into a solution of compound 2 (0.50 g, 1.6 mmol in 20 mL THF). After
the workup process, compound 2b was isolated via recrystallization out
of methanol (0.65 g, 70%). 1H NMR spectral signals (CDCl3: δ 7.24,
X-ray Structure Determinations. High-quality crystals of com-
pounds 2a, 2b, and 3a were grown from methanol. Single crystals of
appropriate sizes were selected and mounted on a goniometer by
standard methods at room temperature. Data were collected on a Bruker
P4 diffractometer equipped with a SMART CCD detector. Crystal data,
data collection, and refinement parameters are provided in the Support-
ing Information. The molecular structures were elucidated using direct
methods and standard difference map techniques to “solve” the struc-
ture; full-matrix least-squares refinement procedures were performed on
F2 values with the SHELXTL program (version 5.10).39 Some of the
thienyl moieties were found to be crystallographically disordered as
evidenced by distortions in the atomic thermal parameters upon
preliminary least-squares refinement of the full initial solution. Two
ring conformations clearly exist and are related by a rotation of ca. 180°
about their respective CdipyrrinꢀCthienyl or BꢀCthienyl vectors. Such
disorder was previously encountered in related dipyrromethane and
BF2-dipyrrin derivatives.18,35 This disorder was modeled here, as before,
by creating atomic coordinates for a second thienyl group; both “parts”
were satisfactorily least-squares refined. The hydrogens on the solvent
carbon atoms were not added. The *.cif files of crystallographic
determinations have been deposited with the Cambridge Crystallo-
graphic Data center (CCDC 788639 (3a) and 788640 (2a)). These data
are available at www.ccdc.cam.ac.uk/conts/retrieving.html or from the
CCDC, 12 Union Road, Cambridge CB2 IEZ, United Kingdom;
fax þ441223-336033; e-mail: deposit@ccdc.cam.ac.kr. The X-ray struc-
ture of 2b was determined tentatively as well, but this data is not
included here.
3
400 MHz): δ 7.61 (t, JHꢀH = 1.5 Hz, 1Hh), 7.02 (s, 2Hb), 6.92 (d,
3JHꢀH = 3.2 Hz, 2Hl3), 6.90 (d, 3JHꢀH = 3.8 Hz, 1Hi), 6.79 (d, 3JHꢀH = 4.5
3
Hz, 1He), 6.75 (d, JHꢀH = 4.5 Hz, 1Hd), 6.65 (dd, JHꢀH = 3.2 Hz,
4JHꢀH = 1.0 Hz, 2Hm), 6.56 (dd, 3JHꢀH = 4.2 Hz, 4JHꢀH = 1.2 Hz, 1Hf),
6.49 (dd, 3JHꢀH = 3.8 Hz, 4JHꢀH = 1.0 Hz, 1Hj), 6.36 (dd, 3JHꢀH = 4.1
Hz, 3JHꢀH = 1.8 Hz, 1Hg), 2.48 (d, 4JHꢀH = 0.5 Hz, 6Hn ), 2.42 (s, 3Hc ),
0
0
2.40 (s, 3Hk ), 2.20 (d, JHꢀH = 4.6 Hz, 6Ha ). 13C NMR spectral signals
4
0
0
(CDCl3: δ 53.8, 100 MHz): δ 152.1 (td, 1JCꢀH = 8.8 Hz, 2JCꢀH = 2.5 Hz,
1
2
1C5), 150.5 (br, 1C7), 143.5 (dt, JCꢀH = 183.1 Hz, JCꢀH = 8.8 Hz,
1Ch), 143.5 (m, 1C6), 140.7 (m, 2Cn), 138.2 (m [looks like: q, 2JCꢀH 5.9
Hz], 1Cc), 136.9 (m, 1C3), 136.7 (m, [looks like: q, 2JCꢀH = 5.7 Hz] 2Ca),
132.8 (dd, 1JCꢀH = 169.1 Hz, 2JCꢀH = 6.0 Hz, 1Ci), 132.7 (m, [looks like:
q, 2JCꢀH = 8.6 Hz] 1C4), 132.04 (m, 1Ck), 131.1 (br, 1C1), 130.1 (dd,
1JCꢀH = 161.1 Hz, 2JCꢀH = 6.0 Hz, 2Cl), 128.9 (dd, 1JCꢀH = 174.1 Hz,
2JCꢀH = 3.5 Hz, 1Ce), 128.1 (dm, 1JCꢀH = 146.2 Hz, 2Cb), 126.4 (dm,
1JCꢀH = 165.0 Hz, 1Cj), 125.6 (dm, 1JC-H = 169.8 Hz, 3Cm,f), 121.6 (dd,
1JCꢀH = 173.1, JCꢀH = 3.6 Hz, 1Cd), 117.7 (dd, JCꢀH = 173.5 Hz,
Computational Details. The Gaussian 03 program40 was used for
all calculational work provided in the Supporting Information. All
geometries were processed in silico in the gas phase at 0 K. Hardware
used involved an in-house Intel Pentium IV 3.0 system. Molecular
orbital images were obtained through the use of Gauss View 3.0. This
following protocol was used for all calculations: (i) input geometries
were prepared from the crystallographic atomic coordinates where
possible or by careful modification of closely related geometries by
scientific graphics software and invoking chemical intuition. (ii) Density
functional theory (DFT) geometry optimizations were performed at the
B3LYP level41,42 with a combination of basis sets: Lanl2DZ43 for Cu;
6-31G(d)44 for N and S; 3-21G45 for C, H, B, and F. (iii) Vibrational
frequencies were determined for all geometries, and negative ones were
found to be absent signifying that a true minimum was found.
Isothermal Titration Calorimetry (ITC) Binding Studies. A
VP-ITC instrument manufactured by MicroCal, Inc. was used to
determine the molar enthalpy (ΔH) of complexation. Titrations were
performed at 25 ( 0.01 °C. Blank titration samples were also measured
in plain solvent, and this data was subtracted from the corresponding
titration so as to remove from consideration any effect associated with
heats of dilution involving the titrant. The actual experiment consisted of
filling the sample cell with a host solution, filling the syringe with a
solution of HgClO4, and titrating via a computer-automated injector.
Subsequent fitting of the data to a 1:1 binding profile using the included
Origin software package provided access to the association constant
Ka and differences in entropy ΔS, enthalpy ΔH, and thus Gibbs free
energy (ΔG).
2
1
2JCꢀH = 8.8 Hz, 2JCꢀH = 3.0 Hz, 1Cg), 21.2 (dd [looks like: q], 1JCꢀH
=
125.4 Hz, 3JCꢀH = 4.4 Hz, 1C ), 20.0 (q, 3JC_-H = 5.0 Hz, 1Ca ), 15.4 (qd,
0
JCꢀH = 127.2 Hz, 3JCꢀH = 2.4 Hz, 2Cn , 1Ck ). 11B NMR spectral signals
1
0
0
(CDCl3, BF3 OEt2: δ 0.00, 128 MHz): δ ꢀ3.01 (s). MALDI-TOF m/z
3
(Mþ): 562.17 (calcd), 561.65 (obsd). HRMS m/z ((M þ Na)þ):
585.164 (calcd), 585.164 (obsd).
Synthesis of 3a [3,4,4-Tri(2-thienyl))-8-phenyl-4-bora-3a,4a-diaza-
s-indacene]. All processes undertaken to obtain compound 3a were
analogous to those for the synthesis of 1a,18 except for the use of
compound 3 (0.4 g, 1.5 mmol) in place of compound 1. A portion of
2-thienyllithium (6.0 mL, 1.0 M in THF) was added. Finally, compound
1
3a was isolated via recrystallization out of methanol (0.1 g, 14%). H
NMR spectral signals (CD3COCD3: δ 2.05, 400 MHz) are as follows: δ
7.69 (m, 2Ha), 7.66 (m, 2Hb), 7.62 (m,3JHꢀH = 1.43 Hz, 1Hc), 7.60 (m,
3JHꢀH = 1.6 Hz, 1Hh), 7.40 (dd, 3JHꢀH = 5.1, 4JHꢀH = 1.1 Hz, 1Hi), 7.32
(dd, 3JHꢀH = 4.8, 4JHꢀH = 1.0 Hz, 2Hn), 7.14 (d, 3JHꢀH = 4.4 Hz, 1Hd),
7.04 (dd, 3JHꢀH = 3.4 Hz, 4JHꢀH = 1.0 Hz, 2Hl), 6.93 (dd, 3JHꢀH = 3.4
3
Hz, 4JHꢀH = 1.5 Hz, 2Hm), 6.92 (m, 1He), 6.90 (dd, JHꢀH = 3.7 Hz,
4JHꢀH = 1.1 Hz, 1Hk), 6.86 (dd, 3JH_H = 4.3 Hz, 4JHꢀH = 1.2 Hz, 1Hf),
6.75 (dd, 3JHꢀH = 5.1 Hz, 3JHꢀH = 3.8 Hz, 1Hj), 6.50 (dd, 3JHꢀH = 4.3
Hz, 3JHꢀH = 1.9 Hz, 1Hg). 13C NMR spectral signals (CD3COCD3: δ
30.0, 100 MHz): δ 152.9 (m, 1C5), 145.7 (s, 1C2), 145.3 (dt, 1JCꢀH
=
2
183.6, JCꢀH = 8.9 Hz, 1Ch), 137.5 (m, [looks like: t, 2JCꢀH = 8.8 Hz]
1C3), 135.3 (m, 1C1), 134.9 (m, 1C6), 133.7 (m, [looks like: q, 2JCꢀH
8.7 Hz] 1C4), 132.5 (dm, 1JCꢀH = 169.5 Hz, 1Ck), 131.5 (dm, 1JCꢀH
178.6 Hz, 1Cd), 131.3 (dm, 1JCꢀ1H = 170.2 Hz, 2Cl), 131.2 (dm, 1JCꢀH
=
=
=
172.3 Hz, 2Cb), 131.1 (dm, JCꢀH = 180.9 Hz, 2Ca), 129.8 (dm,
1
1JCꢀH = 186.1 Hz, 1Ci), 129.3 (dm, JCꢀH = 200.4 Hz, 1Cc), 128.8
’ RESULTS AND DISCUSSION
(dm, 1JCꢀH = 173.7 Hz, 1Cf), 128.0 (dm, 1JC1ꢀH = 168 Hz, 1Cj), 127.9
1
Three new BODIPY “scorpionate”-like species 2a, 2b, and
3a were synthesized in accordance with previous synthetic proto-
cols (Scheme 1)18 and fully characterized by various methods
(dm, JCꢀH = 170.7 Hz, 2Cm), 127.4 (dm, JCꢀH = 164.9 Hz, 2Cn),
122.7 (dd, 1JCꢀH = 172.0 Hz, 2JCꢀH = 5.4 Hz, 1Ce), 119.1 (ddd, 1JCꢀH
=
2
2
174.0 Hz, JCꢀH = 8.7 Hz, JCꢀH = 3.8 Hz, 1Cg). 11B NMR spectral
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Scheme 1. (Top) Structures of Related Compounds That Have Been Previously Reported.18,35 (Bottom) Preparation of
“Scorpionate-Like” BODIPY Derivatives and the Positions of Methylationa
a THF was used as a solvent at -78 °C for the salt metathetic reaction that forms compounds 2aꢀ3a.
(vide infra). While they can be commonly referred to as dipyrrin
species, rigorous boradiazaindacene complex naming is also
customary and preferred by some practioners: 3,4,4-tris(5-R-
(2-thienyl))-8-(2,4,6-R0-phenyl)-4-bora-3a,4a-diaza-s-indacene
(R, R0 = H, 3a; R = H, R0 = Me, 2a; R = Me, R0 = Me, 2b). These
three compounds are the first 8-phenylscorpionate-type deriva-
tives to be synthesized.18 The synthesis of the BF2 derivatives 3
and 2 was performed as previously reported46 and was analogous
to that for 1. Chromatography was used extensively for purifica-
tion purposes again, analogous to what was described before for
related species. The pure products are easily characterized by
their bright red appearance, fluorescence (TLC assays), and
respective mass spectrometric (m/z) values of 520.64, 561.65,
and 478.32 that correlate well with the respective calculated
values. With various 1-D and 2-D NMR spectroscopic techni-
ques, the purity of 2a, 2b, and 3a can be determined. While the
methyl groups for 2a and 2b are easily assigned, conformation
and assignment of the sp2-hybridized carbon resonances were
also possible. While some 1H assignments were made conveni-
ently by analogy to those reported previously in closely related
sytems,22 some differences exist here. First, we simply demon-
strated that boron was present; support in solution for boron
in 2a, 2b, and 3a comes from the clear assignable singlets in
the 11B NMR spectra, respectively, at δ ꢀ2.00, ꢀ3.01, and ꢀ1.99
ppm (see the Supporting Information for reproductions of these
protons. Lastly, the quaternary carbons were further scrutinized
with the help of 1Hꢀ C HMBC NMR spectra (see the
13
Supporting Information).
Optical Properties. Compounds 2aꢀ3a are red green
(dichroic) crystalline solids stable on the bench-top as powders
in (moist) air for more than one year. Dissolution of these
complexes into various solvents gives rise to green fluorescent
red solutions, characteristic for BODIPY systems. The principal
optical features are revealed in Figure 2 (properties are tabulated
in the Supporting Information). Briefly, the original brilliant
fluorescence intensity for 2 (ΦF = 0.93, toluene)32 carries over
partly to 2a (ΦF = 0.27 ( 0.013, acetonitrile). Compound 2a,
which is by far the most fluorescent of the three, is shown in
solution (photographs, Figure 2); it is promising in that closely
related systems were soluble in 50% water (MeCN/H2O, 50:50
by vol.).35 Formal incorporation, or removal, of methyl groups
gives 2b (ΦF = 0.024 ( 0.0016) and 3a (ΦF = 0.0034 (
0.00047). The Ph/mesityl 8-substitution difference in these
“scorpionate-like” units is parallel to that difference between
the parent difluoroboryl species: ΦF = 0.053-0.062 vs 0.93
(toluene).32 Interestingly, 2b is weakly fluorescent. Why methy-
lation at the “head” thienyl groups for 2b gives a formal decrease
in ΦF value might be rationalized by the fact that the methyl
groups enhance non-radiative pathways directly or may constrain
highly emissive conformations. In any event, the fluorescence
lost by such formal thienyl substitution can be retrieved upon
selective heavy atom binding (chelation-enhanced fluorescence),
1
and all other spectra). Next, in H and 13C NMR spectra, the
overall correct number of peaks is present, according to the
structures provided in Scheme 1. Further, the requisite number
as observed in the 1a Cu2þ case in which the ΦF value of the
3
1
1
of cross-peaks in the 2-D Hꢀ H COSY spectra exists, as well
fluorophorecomplex increased dramatically from 0.012 to 0.194.18
Optical Changes upon Mnþ titration. A range of metal ions
was used for 2aꢀ3a in screening for Mnþ recognition as performed
1
13
(Supporting Information). Also, the Hꢀ C HMQC spectra
conveniently show cross peaks for the correct number of anticipated
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Figure 2. (Left) Normalized UV-vis absorption and emission spectra and (upper right) photos of four species (1a, 2a, 2b, and 3a) under UV irradiation
(365 nm) in acetonitrile. (Lower right) The same vials and samples shown under white light: 10 μM. The tetrathienyl-containing species 1a is used as a
reference.18
Figure 3. Full plots of λabs,max and λem,max values as a function of equivalents of analyte. Changes of the absorbance and emission intensity are shown
upon Cu2þ and Hg2þ titration with compounds 1aꢀ3a. 1aꢀ3a = 2.68 ꢁ 10ꢀ5 M; Cu2þ = 4.45 ꢁ 10ꢀ3 M; Hg2þ = 3.78 ꢁ 10ꢀ3 M, acetonitrile solvent.
UVꢀvis and emission spectra were acquired immediately after sample preparation.
previously for similar BODIPY species.47 The perchlorates of
Cu2þ and Hg2þ were used and led to UVꢀvis and emission
spectral changes shown in Figure 3; photos of the vials are shown
in Figure 4. The emission spectral changes upon addition of
titrants are as follows: 2a, which is greatly fluorescent, loses its
fluorescence evenly and significantly between 0 and 3 equiv of
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Figure 5. Emission intensity of 2a (5.0 ꢁ 10ꢀ6 M, green bars) with
5 equiv of Cu2þ (blue bars) or Hg2þ (red bars) with various metal ions
(10 equiv) in acetonitrile.
Colorimetrically, in the UVꢀvis spectra (Figure 3, top) there
is “turn-off” optical behavior for all species (2a, 2b, and 3a) with
Cu2þ. Saturation occurs generally in the range of 5ꢀ7 equiv of
Cu2þ. For Hg2þ, there is a “turn-on” response for all species
(1aꢀ3a) to about 2ꢀ3 equiv. Compounds 2a and 3a, along with
the previously measured 1a, have larger λmax absorbance in-
creases, whereas 2b gives a more modest increase. Due to the
natural brightness of color, we examined the colorimetric cap-
abilities at low concentration, stepping down by factors of 10 in
concentration from what were described above (Figure 3). The
limits of detection in compounds 2aꢀ3a for Cu2þ and Hg2þ
were calculated. For Cu2þ, compounds 2a, 2b, and 3a have the
values of 1.2, 0.71, and 1.6 μM, respectively. For Hg2þ, the values
are 1.6, 1.6, and 2.2 μM, respectively. Binding constants were also
obtained from these spectrometric titration results. The values
obtained are as follows: 1.10 ꢁ 104 ( 1170 Mꢀ1 for 2a Cu2þ
,
3 3 3
4.18 ꢁ 103 ( 1080 Mꢀ1 for 2b Cu2þ, and 2.92 ꢁ 104 ( 4050
3 3 3
M
ꢀ1 for 3a Cu2þ
.
Next, we determined the selectivity of metal ions for receptor
3 3 3
2a. Compound 2a can be considered as a formal intermediate
when considering its degree of methyl substitution compared to
that for derivatives 2b and 3a. Specifically, solution metal ion
sensing competition studies were performed with Cu2þ and
Figure 4. Digital photos of 1aꢀ3a in acetonitrile solution after addition
of 5 equiv of metal ion: (top) naked eye detection; (bottom) use of
fluorescence (lamp with bulb giving emission at 365 nm). Concentra-
tions of ligand (10 μM), Cu2þ (50 μM), and Hg2þ (50 μM).
Hg2þ versus other available various metal cations (Agþ, Ca2þ
,
Cd2þ, Co2þ, Fe2þ, Mg2þ, Mn2þ, Pb2þ, and Zn2þ) (Figure 5).
After the addition of 5 equiv of Cu2þ to compound 2a, the
fluorescence was quenched. In the presence of 10 equiv of other
metal ions, the solutions of 2a still gave high fluorescence.
However, after the addition of 5 equiv of Cu2þ to 2aꢀmetal
ion mixture, the fluorescence was again quenched. These results
mean that Cu2þ ion binding to 2a is predominant over the other
metal ions (blue bars). This phenomenon also occurs for the
Hg2þ ion case in which fluorescence quenching occurs in the
presence of other metal ions (red bars) but to a lesser extent than
titrant. This tailing off of fluorescence intensity after 3 equiv leads
to very little remaining fluorescence at 5 equiv. This trait is found
for both ions Cu2þ and Hg2þ. The behavior of 2b starts with a
very small increase between 0 and 1 equiv of Cu2þ titrant,
followed by a general turn-off behavior until equiv ∼5 (where the
measurement stopped). This same species responds in a “turn-
on” fashion when in the presence of Hg2þ, giving the essential
opposite effects, differences that signify the essence of this study.
Further, compound 3a gives a “turn-on” response from 0 to 5.5
equiv of Cu2þ titrant and allows for a 6.3-fold increase, reaching
saturation at ∼5.5 equiv of Cu2þ; a “turn-off” response is then
seen from 5.5 to 16 equiv of Cu2þ. For 3a with Hg2þ, however,
there is a direct “turn-off” response starting from 0 to 3 equiv.
This fluorescence increase found here for Hg2þ through methyl
substitution is significant, considering the various photophysical
quenching mechanisms possible for this ion when in contact with
fluorogenic groups.11 Even at higher equivalency, the onset of
potential collisional quenching due to the increase in the con-
centration of Hg2þ is very gradual. For example, in the mixture of
3a þ Hg2þ, the reliability in the fluorescence detection signal
appears to exist over the course of hours and days in this assay.
for Cu2þ
.
In the presence of both Cu2þ and Hg2þ, the 2a compound
solution (acetonitrile) absorption spectrum shows a predictable
λabs,max decrease at 551 nm (see the Supporting Information).
This observation is the same as the consequence of 2a Cu2þ
3 3 3
binding; 2a Hg2þ binding is typically evidenced by a new
3 3 3
absorbance λabs,max peak at 543 nm, but there was no appearance
of this peak. Therefore, Cu2þ binding with compound 2a is more
dominant than that for Hg2þ, even though a higher Hg2þ
concentration is present.
Job Plots, DFT Geometry Optimization Calculations, Bind-
ing Thermodynamics, and H NMR Spectroscopic Studies.
1
The optical changes presented and discussed so far allow for
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Figure 6. (Top) Job plot analysis for ligands 1a, 2a, 2b, and 3a with Cu2þ (top left) and Hg2þ (top right). Y-axis of graph = Δ(ε ꢀ ε0) ꢁ mole fraction of
receptor (1aꢀ3a) (ε: absorption coefficient of ligand with target ions, ε0: absorption coefficient of ligand without target ions). (Bottom) Geometric
structures from high-level DFT geometry optimization calculations of compound 1a showing variations of Cu2þ binding into the [SSS] core with 1, 2, or
3 corresponding coordinated MeCN solvent molecules (gray = carbon, yellow = sulfur, blue = nitrogen, red-orange = copper).
various further analysis through the use of other techniques.
Namely, (i) Job plots for 1a and 2aꢀ3a, (ii) DFT geometry
optimization calculations of 1a-Cu2þ, (iii) binding thermody-
effect in the [SSS] pocket toward metal ion sensing. Through
Job’s plot analysis, compound 2b showed a ∼1:1 (or perhaps
a ∼3:2) binding stoichiometry which accounted for the fluores-
cence emission saturation patterns observed spectrally for 2b
with both metal ions (Cu2þ and Hg2þ) (Figure 3). Compound
2b shows fluorescence emission saturation for both Cu2þ and
Hg2þ distinctively different from what we would predict from the
straightforward [SSS] pocket binding structure of 2a as shown
1
namics for 2a using ITC measurements, and (iv) H NMR
spectroscopic evidence of complex formation with 2b were
obtained. An analysis of metal ion binding by Job’s method
appears in Figure 6 (top). For the three complexes, the various
stoichiometries were determined: 1a:Cu2þ = 3:2 or 1:1, 2a:
Cu2þ = 1:1, 2b:Cu2þ = 1:1 or 3:2, 3a:Cu2þ = 1:1, 1a:Hg2þ = 2:1,
2a:Hg2þ = 1:1, 2b:Hg2þ = 3:2 or 1:1, 3a:Hg2þ = 1:1. The
occasional discrepancy from 1:1 suggests that the ligand might
occasionally form a sandwich compound (L M2þ L) or
for Cu2þ 1a (Figure 6). It is likely that the methyl-substituted
3 3 3
[SSS] pocket provides a more sterically hindered site for certain
metal ions; the mesityl group at the 8-position might also place
further sterical obligations on the conformations necessary for
chelation in the “head” area. Because of these geometrical pro-
perties, enhanced emission could arise from a process whereby
the methyl groups attached to the thienyl rings are locked out of
certain conformations until metal chelation is effected, which
then gives chelation enhanced fluorescence (CHEF) as observed
in the “turn-on” responses found for Hg2þ with 2b.
3 3 3
3 3 3
some different unanticipated chelation forms in solution.
Interestingly, these molecules have recognition for Cu2þ and
Hg2þ in acetonitrile through the use of the 2-thienyl pocket
which accommodates a simple metal ion in both cases of Cu2þ
and Hg2þ. However, the thienyl group at the 8-position might
also interact with guest cations, as reflected by compound 1a
having a hypothetical binding stoichiometry of ∼3:2 for Cu2þ or
even a value of 2:1 for Hg2þ. We also considered the methyl
Separately, DFT calculations were undertaken to try to analyze
the proposed binding site at the atomic level when engaged in
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Figure 7. (Left) ITC measurements of 2a (3.85 mM) with Hg(ClO4)2 in acetonitrile at 25 °C. Plot of μcal/s values obtained for times 0ꢀ330 min.
(Right) Plot of changes in kcal mol-1 as a function of injectant in which Ka was determined as 3120 ( 307 Mꢀ1
.
[CD3CN:CDCl3 = 2:1 by volume] with 0.0052 M concentration
of Cu2þ and Hg2þ and a 0.0052 M concentration of 2b, new
peaks appear in the Hg2þ sample, tentatively assigned to Hg2þ
3
2b. For Hg2þ, there are instant dramatic changes in which, e.g.,
ligand peaks at δ 6.5ꢀ7.5 are completely consumed upon addition
of Hg2þ (Figure 8); new peaks in the range of 6.3ꢀ8.0 appear in
line with discrete pyrrolyl and thienyl peaks arising from parti-
cular interactions with the metal ion. The loss in concentration of
2b is not concomitant with the growth of new signals in the 1H
NMR spectrum. Overall, a loss of detectable species is apparent
(increased relative noise). Some new clear peaks exist for the
Cu2þ sample; there appear to be some paramagnetic species
forming as well. Unfortunately, at longer times, there is some
evidence of peaks assigned to free thiophene. Thus, while there
may be (in)stability issues at higher concentration, when con-
sidering Cu2þ, there is sufficiently clear information early in the
titration when considering the Job plots and the ITC measure-
ment data that point to complex stability at shorter times.
Structural Data of 2a and 3a. Crystals of 2a and 3a were
obtained for X-ray diffraction through their growth and precipi-
tation out of methanol solution. The molecular structures of 2a
and 3a were obtained via single-crystal X-ray diffraction in space
groups C2/c and P21/n, respectively (Figure 9, top and middle).
All bond distances and angles are provided in the Supporting
Information. A tentative crystal solution of 2b was also obtained
but is not included herein. The molecular structures for 2a and 3a
confirm the proposed structures strongly supported by various
types of solution NMR spectroscopy (vide supra). Namely, the
presence of three, and not four, thienyl groups at the “head”
position was confirmed. The isolation of an impurity product
bearing four thienyl groups (3,4,4,5-tetrathienyl) is possible;
careful separation via PTLC is thus required. In 2a and 3a, the
many aryl groups allow for a consideration of angles between the
calculated mean planes (Figure 9, bottom). Most such dihedral
angles are not discussed here in deference to limiting the
Discussion to the most important aspects. Importantly, the most
telling interplanar angle is that for the 8-position angle: the
dihedral angle between the BODIPY main framework (N1, N2,
C1ꢀC9) and the aryl ring (non-H) atoms is 75.4° for 2a, 80.8°
for 2b, and 60.7° for 3a. Another issue related to metal binding is
whether the “head” thienyls are either preorganized or predisposed
toward metal chelation. It is sterically reasonable, however, to have
the sulfurs pointing toward each other, so as to minimize thienyl
methine group congestion and collisions. However, solid-state
Figure 8. Stack-plot of 1H NMR spectra for the treatment of 2b with
Hg2þ at 5.2 ꢁ 10ꢀ3 M concentration. See the Supporting Information
for more data.
metal binding. The input 1a structures of complexes [[S,S,S]
3
Cu2þ MeCN] [[S,S] Cu2þ 2MeCN] and [[S,S,S] Cu2þ
3
3
3
3
3
3
MeCN] were prepared in silico from structural coordinates of the
ligand and were subjected to theoretical geometry optimization.
Their fully optimized molecular structures appear in Figure 6
(bottom). A preliminary molecular orbital analysis was also per-
formed and is included in the Supporting Information. These
complexes show that the metal ion sits quite stable in the [SSS]
pocket along with a certain designated number of manually oriented
η-1-bound MeCN solvent molecules. The computational stability of
these fragments further supports the existence of a believably versatile
coordination pocket. Interestingly, the tridentate chelation leads to a
“chiral propeller”-type arrangement of the thienyl substituents.
In further considering the [SSS] binding site for these com-
pounds, ITC methods were explored for the association of 2a
with Hg2þ in solution at mM concentration (Figure 7). An
equilibrium value (Ka) for the association was determined to be
3120 ( 307 Mꢀ1. The values for ΔH (ꢀ2.212 ꢁ 104 ( 783.5
kcal molꢀ1) and ΔS (ꢀ60 eu) were also obtained directly.
Changes are seen to arise from a related set of 1H NMR spec-
trosopic studies involving 2aꢀ3a in M2þ titrations. In a sealed J.
Young tube for NMR spectroscopy (constant solution volume)
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high-resolution mass spectrometry, and theoretical calculations
of three new closely-related thienyl-derivatized scorpionate
BODIPY-type species [3,4,4-tris(5-R-(2-thienyl))-8-(2,4,6-R0-
phenyl)-4-bora-3a,4a-diaza-s-indacene (R, R0 = H, 3a; R = H,
R0 = Me, 2a; R = Me, R0 =Me, 2b)]. We have discovered that, to
the best of our knowledge for the first time in fluorophore
chemistry, very minor substituent (i.e., Me f H; H f Me)
directing “turn-on” or “turn-off” fluorescence intensity behavior
at low concentration with metal ions. This characterization and
analysis was done in the context of Cu2þ and Hg2þ solution
detection. The limits of detection were calculated to be in the
range of 0.7ꢀ1.6 μM for Cu2þ and 1.6-2.2 μM for Hg2þ. An
understanding of receptor binding has been characterized by Job
plot analysis, ITC (isothermal titration calorimetry) measure-
ments, DFT calculations, and 1H NMR spectrotitrimetric anal-
ysis. Through our study, it is clear that the [SSS] pocket receives a
metal ion. To support the practical use of this design, 2aꢀ3a
were studied by UVꢀvis and fluorescence spectroscopy; 2a was
the most fluorescent by roughly a factor of 10 (ΦF = 0.27 ( 0.013
(2a), 0.024 ( 0.0016; (2b), 0.0034 ( 0.00047 (3a)). Impor-
tantly, at presaturative low [Cu2þ] with 3a (<3 ꢁ 10ꢀ5 M), an
increase (offꢀon; 6-fold) was observed, whereas for 2a, onꢀoff
signaling was observed. At low mercuric ion concentration
([Hg2þ] < 3 ꢁ 10ꢀ5 M), 2b allowed for a 3-fold (offꢀon)
response, and for 2a it decreased (onꢀoff). For (Hg2þ) 2a,
3
the association constant (Ka) was determined to be 3120 (
307 Mꢀ1. Detailed multinuclear NMR spectra were acquired
(Supporting Information) showing various peaks that corre-
spond to all expected protons and carbons. Some NMR methods
1
1
utilized herein included 1Hꢀ H COSY, 1Hꢀ H NOESY,
13
13
1Hꢀ C HMQC, and 1Hꢀ C HMBC spectroscopy; this
allowed for a thorough NMR spectral characterization of these
new BODIPY species. We hope that this report serves as an
impetus for pursuing different metal ion detection studies where
subtle sterics might impart discrete and differing optical effects.
We hope that such advances in sensing can later impact the field
of molecular neurodegeneration research.
’ ASSOCIATED CONTENT
Figure 9. Molecular structures of compounds 3a (top) and 2a
(middle). Ellipsoids are drawn at 20% probability. (Bottom) The various
mean planes (mplns) for the dipyrrin species discussed herein. 3a:
CCDC 788639; P21/n, unit cell parameters: a = 8.5287(6) Å, b =
9.1106(7) Å, c = 30.020(2) Å, β = 95.135(5)°. 2a: CCDC 788640; C2/c,
unit cell parameters: a = 17.2235(18) Å, b = 21.909(2) Å, c = 16.217(3)
Å, β = 115.963(3)°.
S
Supporting Information. X-ray crystallographic data for
b
compounds 2a and 3a (CIF). Photophysical data of compounds
1a, 2a, 2b, and 3a. H, 13C, and 11B NMR spectra and H-1H
1
1
COSY, H-1H NOESY, H-13C HMQC, and H-13C HMBC
NMR spectra. High-resolution MALDI-TOF mass spectra and
elemental analysis data. Energy diagrams and selected molecular
orbital diagrams. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
1
1
analysis reveals no particular conformer arrangement when
considering one BODIPY molecule at a time (not a packing
scheme); in fact, the observed conformations might arise from
simple crystal packing requirements with neighboring molecules.
Separately, the obliqueness of mean plane 10, relative to mean
plane 4 (or mean planes 5 and 6) might influence electronic
delocalization. If mean planes 10 and 4 remain coplanar, which
could occur upon metal ion binding, such resulting electron
delocalization may thus create different electronic and thus could
be related to the observed fluorescence properties and fluores-
cence switching patterns.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: dchurchill@kaist.ac.kr.
’ ACKNOWLEDGMENT
D.G.C. acknowledges research support from NRF (Grant No.
N01090203) and from the High Risk High Return Project
(HRHRP) at KAIST (Grant No. N10100016). Mr. Hack Soo
Shin is again gratefully acknowledged for his help in acquiring
NMR spectroscopic data. MALDI-TOF data were gratefully
obtained with the help of the KAIST Research Supporting Team.
Teresa Linstead (Cambridge, U.K.) is thanked for her assistance
’ CONCLUSION
Herein, we report the synthesis, multinuclear NMR spectro-
scopic characterization, crystallographic structural characterization,
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in efficiently filing structures CCDC 788639 (3a) and 788640
(2a). W. A. Goddard is thanked for helpful discussions related to
prospective solution/calculation work of 2a and 3a during his
continued stay at KAIST, funded by the World Class University
(WCU) Program.
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