Allosteric regulation in carbon monoxide (CO) Release: Anion Responsive CO-Releasing Molecule (CORM) Derived from (Terpyridine)phenol Manganese Tricarbonyl Complex with Colorimetric and Fluorescence Monitoring

Article abstract of DOI:10.1021/acs.inorgchem.9b00984

A new CO-releasing terpyridine based manganese(I) tricarbonyl complex, [MnBr(CO)₃(terpy-C₆H₄OH)] (1·Mn-OH) functioning via light has been reported. For the first time, we have demonstrated the allosteric regulation concept

Full text of DOI:10.1021/acs.inorgchem.9b00984

Article
pubs.acs.org/IC
Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
Allosteric Regulation in Carbon Monoxide (CO) Release: Anion
Responsive CO-Releasing Molecule (CORM) Derived from
(Terpyridine)phenol Manganese Tricarbonyl Complex with
Colorimetric and Fluorescence Monitoring
Rahul Sakla,† Ajeet Singh,‡ Rahul Kaushik,† Pawan Kumar,† and D. Amilan Jose*,†
†Department of Chemistry, NIT-Kurukshetra, Kurukshetra-136119, Haryana, India
‡Department of Chemistry, Prof. Rajendra Singh (Raju Bhaiya) Institute of Physical Sciences for Study and Research, V. B. S.
Purrrvanchal University Jaunpur, U.P., India
S
* Supporting Information
ABSTRACT: A new CO-releasing terpyridine based
manganese(I) tricarbonyl complex, [MnBr(CO)3(terpy-
C6H4OH)] (1·Mn-OH) functioning via light has been
reported. For the first time, we have demonstrated the
allosteric regulation concept to control the CO-releasing
properties of a CO-releasing molecule (CORM). Fluoride ion
is reported to function as an allosteric activator to control the
rate of CO release in the CORM. Complex 1·Mn-OH
represents an interesting new class of CO-releasing system
that releases CO upon irradiation with blue light (410 nm)
over a period of 40 min with the half-time of 9.8 min. Fluoride
ion selectively binds to the phenol moiety of the complex
through hydrogen bonding and deprotonates to phenolate with a color change. Interestingly in the presence of fluoride ion, the
rate of CO release is fast with the half-time of less than a minute. The rate of CO release is allosterically regulated by fluoride
anion and can be monitored through a color change, fluorescence, and absorption based spectral changes along with IR studies
and myoglobin assay.
However, the most commonly used stimulus to turn on CO
release is light. Many photosensitive metal carbonyl complexes
were studied to this end.16−21 Despite significant develop-
ments, stimuli-responsive CORMs for biological applications
and allosteric regulation/activation for CO release are not
known.
Allosteric regulation is a well-known biological phenomenon
and extensively used in nature.22 In general, binding of a ligand
or any analyte at the remote site of enzymes modifies the
performance at a distant site through structural or dynamic
changes.23 In biological systems, allosteric regulation controls
the structure and catalytic efficiency of many enzymes. In
nature, allosteric regulation has been afforded by combining
the conformational changes to the structure upon binding of
specific coordinating analytes. Although the light-induced
release of CO has received much attention among researchers
because of its noninvasive, cheap, and controlled delivery, still
it remains unexplored to manipulate CO delivery by the
allosteric external regulator.
INTRODUCTION
■
Carbon monoxide (CO) is a small molecule bioregulator along
with hydrogen sulfide (H2S) and nitric oxide (NO).1 The role
of CO has been confirmed in various therapeutic and
pharmacological studies such as myocardial infarction, organs
transplantation procedures, cardiovascular disease, and anti-
bacterial and anticancer activity.2 Therefore, for future
therapeutic applications, CO seems to have a high potential
value.3 But for therapeutic applications temporal and control
delivery of CO is extremely important.3−5 In this regard, “CO-
releasing molecules” (CORMs) are gaining much attention
and appeared as an important topic,6−8 that bridges
interdisciplinary research extending from chemistry to biology
and medicine.9−11
The increasing interest in CORMs among researchers is due
to the fact that they allow the controlled and targeted delivery
of the CO gas into specific sites of the biological targets.
Generally, CORMs are activated by various external stimuli,
based on the way in which CO release is activated; it can be
classified into solvent-triggered CORMs, photoactivated
CORMs (PhotoCORMs),9,12 enzyme-triggered CORMs
(ET-CORMs),13 thermal-triggered CORMs, oxidation-trig-
gered CORMs,14 and pH-triggered CORMs.15
Herein, we have demonstrated a first proof-of-concept that
uses a bioinspired allosteric regulatory mechanism to control
Received: April 4, 2019
© XXXX American Chemical Society
A
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intervals was recorded after irradiation with light (410 nm) in a
standard quartz cuvette cell of length 1 cm.
the rate of CO release along with a potential application in the
construction of molecular logic gates. In brief, a novel insight
into the CO release of CORMs by allosteric activation has
been uncovered.
Selectivity Studies with F−, Cl−, Br−, I−, and acetate. All the
anion stock solutions were prepared of concentration 1 × 10−2 M in
acetonitrile. In 2 mL of 1·Mn-OH (20 × 10−6 M) solution, anions
such as F−, Cl−, Br−, I−, acetate (3 × 10−5 M each) were added
individually and the change in absorbance was recorded.
Terpyridine based new Mn(I) carbonyl complex, [MnBr-
(CO)3(terpy-C6H4OH)] (1·Mn-OH), that releases CO under
the control of blue light irradiation has been discussed. CO
release could be monitored by virtue of simple color change or
by changes in the UV−vis and fluorescence intensity.
Compound 1·Mn-OH can also act as a selective sensor for
fluoride ion in CH3CN with good sensitivity. Importantly, the
rate of CO release by 1·Mn-OH can be regulated via fluoride
ion binding through allosteric activation. Although, a non-
substituted simple terpy ligand based manganese(I) tricarbonyl
complex has already been studied for CO release,12 the
allosteric regulation of CO release by fluoride ion is not
described.
Titration of 1·Mn-OH with F−, Cl−, Br−, I−, and acetate. Two
mL of 1·Mn-OH (20 × 10−6 M) solution was prepared by taking
0.109 mL of 1·Mn-OH (3.6 × 10−4 M) in acetonitrile solution. The
UV−vis spectrum was recorded with different concentrations of F−,
Cl−, Br−, I−, and acetate (0−60 × 10−6 M) in a standard quartz
cuvette cell of length 1 cm.
Myoglobin (Mb) Assay. For myoglobin assay 1·Mn-OH (1.8 ×
10−3 M) stock solution was prepared in acetonitrile. A stock solution
of myoglobin (66 μM) was prepared in phosphate buffer (pH = 7.4,
50 mM). Sodium dithionite (0.1%) was added to convert Mb to
deoxy-Mb prior to each reading. A two-compartment vial was
designed to keep the myoglobin solution and 1·Mn-OH solution
separately. The vial was closed with septa, and all the oxygen was
removed by evacuating air with vacuum and filled with nitrogen, and
the same was performed for 5 times to remove all oxygen. Two mL of
deoxy-Mb was added in one compartment through a syringe and 2
mL of 1·Mn-OH (1.8 × 10−3 M) solution to another compartment.
After irradiation with 410 nm light in different time intervals, 300 μL
myoglobin solution was taken out with a syringe in a small cuvette
having path length 1 cm and the UV−visible spectrum was recorded
immediately.
EXPERIMENTAL SECTION
Instrumentation and Methods. H NMR was measured on a
■
1
Bruker Avance 400 MHz. The mass spectrum was measured on a
Waters Q-Tof mass spectrometer. UV absorption spectra were
recorded on an Evolution 201 UV−vis spectrophotometer using
quartz cells of 1.0 cm path length. A Cary Eclipse fluorescence
spectrophotometer was used to record the fluorescence spectra. FT-
IR experiments were performed by using a SHIMADZU infrared
Calculation of Half-Time (t1/2) and Rate Constant (k). The
rate constant of CO release was calculated by fitting data to the first
order kinetic equation as shown below. The natural logarithm of the
absorption value of 1·Mn-OH at 311 nm was plotted against time.
Then the linear curve was plotted and the value of slope was
calculated which gives the rate constant. Half-time was calculated
using the equation
̈
spectrophotometer. A Drager Pac 7000 portable CO detector has
been used for the CO measurements.
Materials and Reagent. 4-Hydroxybenzaldehyde, 2-acetylpyr-
idine, and bromopentacarbonylmanganese were purchased from
Sigma-Aldrich; silica gel 100−200 mesh was purchased from Avra
chemicals private limited. Other chemicals were purchased from Loba
Chemie or Merck limited unless mentioned otherwise. Solvents used
were analytically pure and used without further purification.
ln 2
k
t1/2
=
Synthesis of 1·Mn-OH. 50 mg of 4-([2,2′:6′,2′′-terpyridin]-4′-
yl)phenol (0.154 mmol) was dissolved in 25 mL of hot solution of
THF. To this solution bromopentacarbonylmanganese (Mn(CO)5Br)
(55 mg, 0.2 mmol) was slowly added and the reaction mixture was
stirred under N2 atmosphere at 60 °C for 5 h in dark condition.
During this period, the color of solution changed from yellow to
orange. The mixture was allowed to cool to room temperature. Half of
solvent was evaporated from the reaction mixture and the yellow color
precipitate was filtered under vacuum and washed with cold ethanol
and methanol. Yield: 65.5 mg (78%). Elem Anal. Calc. for
C24H15N3O4MnBr·CH3OH: C 52.11; H 3.32; N 7.29; O 13.88
where, t1/2 is the half-time and k is the rate constant.
Computational Methods. Optimization, electronic transition,
and HOMO−LUMO of 1·Mn-OH and 1·Mn-O− species were
performed by using the density functional theory (DFT) method. For
different calculations, the Mn atom was performed by employing the
LANL2DZ basis set and effective core potential (ECP) and the Pople
6-311G* split-valence triple-ζ basis set with polarization was used for
Br and other atoms. Electronic transition energies and oscillator
strengths were then calculated for 1·Mn-OH and 1·Mn-O− at B3YLP-
optimized geometries using time-dependent density functional theory
(TDDFT). For TDDFT calculations, we have considered the solvent
acetonitrile by using the Polarized Continuum Model (PCM) for the
anionic and neutral species, respectively. The different calculations
were executed with Gaussian 09, and molecular orbitals were
visualized by using Gauss View 5.08.
1
Found: C 51.94; H 3.21; N 7.01; O 12.76. H NMR (400 MHz,
D6DMSO) δ 10.15 (s, 1H), 9.22 (d, 1H, J = 5.16 Hz), 8.97 (d, 1H, J
= 7.56 Hz), 8.90 (s, 1H), 8.79 (s, 1H), 8.27 (t, 1H, J = 7.72 Hz), 8.06
(dd, 4H, J = 14.75, 6.50 Hz), 7.94 (d, 1H, J = 7.53 Hz), 7.72 (t, 1H, J
= 5.96 Hz), 7.61 (t, 1H, J = 5.82 Hz), 6.95 (d, 2H, J = 8.02 Hz);
FTIR wavenumber (cm−1): 2023 and 1930 cm−1 corresponding to
CO stretching). ESI-MS m/z: [M + H]+ and [M + H + 2]+ (1:1)
Calculated: 543.97 and 545.97, Experimental: 543.99 and 545.98
(1:1) (100%). HR-MS: [M + H]+ Calculated: 543.9705, observed:
543.9702.
RESULTS AND DISCUSSION
■
Ligand 1 was synthesized by an earlier reported method.24
Manganese(I) complex 1·Mn-OH (Scheme 1) was prepared
by making ligand 1 react with [Mn(CO)5Br] under reflux
condition in THF. Routine analytical techniques such as
CO Release Studies of 1·Mn-OH and 1·Mn-O− with Light.
1·Mn-OH (3.6 × 10−4 M) stock solution was prepared in acetonitrile.
To study CO release, 2 mL of 1·Mn-OH (20 × 10−6 M) solution was
prepared by taking 0.109 mL of 1·Mn-OH (3.6 × 10−4 M) stock
solution. The UV−vis spectrum or fluorescence spectrum at different
time intervals was recorded after irradiation with light (410 nm) in a
standard quartz cuvette cell of length 1 cm. The excitation wavelength
310 nm and slit width 5/5 nm were used for fluorescence
measurement.
1
CHNS(O), FT-IR, H NMR, and HR-Mass analysis were
performed to characterize Ligand 1 and complex 1·Mn-OH
(see Supporting Information). Terpyridines (Terpy) often act
as a tridentate ligand, along with other binding modes.
Bidentate coordination is one of the common bonding modes
for terpy that is expected in 1·Mn-OH. In complex 1·Mn-OH,
manganese is coordinated to the central pyridine and one
terminal pyridine between two. Another pyridine remains
unbound.25 The purity and structure of complex 1·Mn-OH
Similarly, 2 mL of 1·Mn-OH (20 × 10−6 M) solution was prepared
by taking 0.109 mL of 1·Mn-OH (3.6 × 10−4 M) stock solution and
diluted to 2 mL followed by addition of (butyl)4N+F− (40 × 10−6 M)
to generate 1·Mn-O−. The UV−vis spectrum at different time
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however, upon irradiation with light the emission intensity
increased and enhanced emission was observed at 410 nm.
Upon CO release, the nonfluorescent complex becomes
fluorescent. 1·Mn-OH is nonemissive due to the Mn(I) center
(low spin d6 electron configuration) attached three electron-
withdrawing CO ligands. However, the fluorescence of the
ligand terpy moiety has been restored after the release of CO
molecules from 1·Mn-OH.
Scheme 1. Synthesis of Complex 1·Mn-OH
Further, the time-dependent IR spectroscopic study has
been performed to examine the CO-releasing behavior of 1·
Mn-OH under light. The intensity of the νCO bands (2037 and
1930 cm−1) decreased upon CO release; after extending
irradiation, the peak disappeared completely (Figure 3). This
clearly indicates loss of all three CO molecules from 1·Mn-OH
upon irradiation with blue light (410 nm) for 60 min. The
light-induced CO release behavior of 1·Mn-OH was also
confirmed by using the myoglobin (Mb) assay. As 1·Mn-OH is
not soluble in water, Mb assay was performed by using two-
compartment vials (see the experimental section in SI). Mb
assay is the standard method for detecting CORM-derived CO
in vitro.26,27
In this method, the liberated CO reacts with deoxy-
myoglobin to give a distinct CO adduct. As shown in Figure
4, the UV−vis peak of deoxy-Mb at 557 nm decreased and the
characteristic peaks of Mb-CO adduct at 540 and 577 nm
raised in the Q-band region after irradiation at 410 nm.
Formation of Mb-CO from Deoxy-Mb (Figure 4) confirmed
the release of CO from 1·Mn-OH.
Phenol and catechol-based compounds are known for the
selective detection of anions, especially for fluoride ion.28,29
The strongest hydrogen bond interaction with fluoride over
F−O−H hydrogen-bonding is accountable for the recognition
of F− ions (Scheme 2). But, with an excess of F− ion, it
produces the anionic form owing to the deprotonation of
−OH group prompted by Brønsted acid−base reaction
(Scheme 1).30,31
In this connection, we have examined the change in the
UV−vis absorption spectrum of 1·Mn-OH in the presence of
several anionic species such as F−, Cl−, Br−, I−, and CH3COO−
in CH3CN. As shown in Figure 5, only with F− ion was a
dramatic change in color (Figure 5B) and UV−vis absorption
spectrum (Figure 5A) obtained. The UV−vis absorption
was confirmed by analytical and spectroscopic data (Figure
S1−4).
The UV−vis absorption spectrum of complex 1·Mn-OH (20
μM) (Figure 1) consists of one soret band at 312 nm and a
weak shoulder at 422 nm. The intense absorption peak in the
312 nm region is assigned to the intraligand π → π* transition
of the Terpy−phenol ligand and 422 nm assumed to be MLCT
(Figure S5).
CO-releasing behavior and suitability of 1·Mn-OH to act as
a new photosensitive CO-releasing molecule was followed by
UV−vis spectroscopy based on the change in the absorption
spectrum.
A CH3CN solution of 1·Mn-OH (20 μM, 2 mL) was
irradiated with blue light (420 nm), and the UV−vis
absorption spectrum was recorded at regular intervals for 70
min. The absorption band at 312 nm was found to be slightly
red-shifted to 317 nm within a minute, and later the band at
317 nm decreased steadily with an associated increase in
absorbance at 285 nm. A systematic change in the UV−vis
spectrum with an isosbestic point at 301 nm indicates
photoinduced CO release of 1·Mn-OH without any apparent
intermediate species. The CO release kinetic experiments upon
irradiation with the light of 420 nm gave apparent rate constant
kCO = 0.07065 min−1 with a t1/2 time of 9.8 min (Figure S6).
The light-induced release of CO was also investigated by
using a fluorescence emission spectrum. The emission
spectrum of 1·Mn-OH was recorded in CH3CN (λexc = 300
nm) under irradiation with blue light for 60 min. As shown in
Figure 2, complex 1·Mn-OH does not show any fluorescence;
Figure 2. Time-dependent emission spectra of 1·Mn-OH (20 μM) in
CH3CN solution during blue light irradiation (410 nm). Time
interval 0−30 min. Inset: Change in emission at 412 nm as a function
of irradiation time.
Figure 1. Time-dependent UV−vis absorption spectra of 1·Mn-OH
(20 μM) in CH3CN solution during irradiation (410 nm) from 0 to
70 min. Inset: Change in absorbance at 311 nm with respect to time.
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Figure 3. Time-dependent FT-IR spectrum of 1·Mn-OH (1.8 mM)
upon blue light irradiation (410 nm).
Figure 5. (A) Change in UV−vis absorption spectra of 1·Mn-OH (20
μM) in the presence of various anions such as F−, Cl−, Br−, I−, and
CH3COO− (40 μM) in CH3CN solution. (B) Colorimetric response
of 1·Mn-OH (20 μM) in the presence of different anions in CH3CN.
Figure 4. Change of reduced Mb to Mb-CO in a solution of 1·Mn-
OH (1.8 mM) and reduced Mb (66 μM) in a two-compartment assay
upon exposure to light (410 nm).
Figure 6. Schematic UV−vis absorption titration of 1·Mn-OH (20
μM) in the presence of the different amount of (butyl)4N+F− ion (0−
60 μM) in CH3CN. Inset: Change in UV−vis at 490 nm as a function
of F− ion concentration.
Scheme 2. (A) Structure of New Complex 1·Mn-OH and
(B) Mechanism of Anion Induced Deprotonation
other groups.28,32These results clearly describe that the F−
recognition capability of the complex 1·Mn-OH is due to a
hydrogen-bonded complex, and deprotonation of OH protons
upon addition of an extra amount of F− anions. After
deprotonation, an increase of the electron density on oxygen
would cause delocalization with the electron-withdrawing
terpyridine unit. Thus, the electrons are rearranged and the
π-electron delocalization extends in the whole molecule
leading to an obvious redshift. This F− ion sensing behavior
matched well with a previous study of phenol functionality
attached to ruthenium and rhenium polypyridyl com-
plexes.28,32,33
spectrum of free 1·Mn-OH displayed a band centered at 312
nm, accompanied by a weak shoulder at 422 nm. Upon
addition of different concentration of F− (0−60 μM), the
absorption band at 312 nm decreased and a new peak appeared
at 490 nm, and simultaneously the color of the solution
changed from light yellow to orange.
Two isosbestic points at 351 and 370 nm were observed
(Figure 6) indicating the formation of 1·Mn-OH···F− complex
and deprotonation of 1·Mn-OH to form anionic form 1·Mn-
O−. This type of observation was already explained by us and
The F− sensing ability of the 1·Mn-OH is attributed to a
hydrogen-bonded adduct, which undergoes acid dissociation in
the presence of excessive F− anions. The deprotonation of
−OH protons with fluoride ion was also confirmed by FT-IR
experiments. The spectral and naked-eye detectable color
changes of 1·Mn-OH upon addition of (butyl)4N+OH−
(Figure S8) were found to be similar to those obtained with
F−; further, it confirms that the interaction between 1·Mn-OH
and F− was the Brønsted acid−base reaction (deprotonation).
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Changes in the UV−vis spectrum with other anions were
also measured. As observed (Figure S9), other anions did not
produce any change in absorption even after the addition of an
excess amount of respective anions and the color of the
solution also remained the same, owing to the weak interaction
between the phenolic −OH group. Mass analysis (ESI-MS) of
1·Mn-OH with and without F− anion was also measured.
Complex 1·Mn-OH shows a peak at m/z = 543.99, matching
with its [M + H]+ molecular mass, whereas the ESI-MS (-ve
mode) of the 1·Mn-OH in the presence of F− anion (4 equiv)
showed a major peak at m/z = 542.01; this indicates the
conversion of phenol-to-phenolate (Figure S10). Further, to
know the effect of anion binding in CO-releasing behavior, we
have investigated the CO-releasing behavior of 1·Mn-OH in
the presence of F− anion. We have recorded time-dependent
UV−vis and luminescence spectra of 1·Mn-OH with F− anion
(1·Mn-O− form) in the presence of light irradiation at 410 nm.
As shown in Figure 7, upon irradiation with light the band at
317 and 494 nm decreases gradually with a concomitant
increase in absorbance at 285 nm. These spectral changes were
obtained within 5 min. On the contrary, without F− anion (1·
Mn-OH only), it took 50−60 min to get the complete
saturation (Figure 1) in the UV−vis spectrum. In the
deprotonated form, the complex releases CO at a faster rate.
Also, the solution color changed from orange-red to pale
yellow (Figure 7B).
obtained within 4 min upon irradiation with light. Con-
sequently, fluoride ion helps in modulating the CO-releasing
properties of 1·Mn-OH. The CO-releasing behavior of 1·Mn-
OH with fluoride ion is also confirmed by time-dependent IR
and myoglobin assay (Figure S12−13). These results are in-
line with UV−vis and emission studies. ESI-mass data analysis
shows that upon irradiation of 1·Mn-OH under light all three
CO molecules release from the metal center and the Mn center
is not bound to the ligand (Figure S14). Binding of F− anion
on one site of 1·Mn-OH controls the rate of CO release on
another site (Scheme 3), it is in great similarity with the
biological allosteric effect in which binding analyte at one site
will affect the performance at a distant site. This is the first
proof of concept demonstration that uses a bioinspired
allosteric regulatory mechanism to control the rate of CO
release.
Consequently, this is the first example that demonstrates a
well-designed case of allosteric regulation in CO release. The
kinetic analysis of the CO release upon irradiation with blue
light (410 nm) with fluoride ion gave apparent rate constant
kCO = 0.80522 min−1 with a t1/2 time of 0.8608 min, which
explicates the fast CO release with fluoride ion (Table S1).
We have also confirmed the CO release of 1·Mn-OH with
and without fluoride ion under irradiation with light by
portable CO detector (Draeger Pac7000). An airtight vessel is
used for the monitoring of CO release under irradiation of blue
light. CO detector displayed the amount of CO release (in
ppm) from 1·Mn-OH at a different interval of time (Figure
S15). As shown in Figure 8, the rate of CO release is faster
with fluoride ion. In addition to the other analytical
experiments, this experiment provides evidence for the fast
release of CO with anion under light.
The colorimetric change enables visual monitoring of CO
release that can be monitored by the naked-eye. The calculated
apparent rate constant of CO release that happened in the
presence of fluoride ion was significantly faster (kCO = 0.805
min−1) as compared to an absence of fluoride ion (kCO
=
0.07065 min−1). These results indicate that in deprotonated
form, 1·Mn-OH will undergo rapid CO release upon
irradiation with light. Fluorescence experiments also confirmed
the fast release of CO in the presence of F− anion (Figure
S11); in deprotonated form, 1·Mn-O− displayed weak
emission and the maximum emission enhancement was
To understand the effect of deprotonation on the CO
release, we have performed DFT calculation of 1·Mn-OH and
its deprotonated form. Molecular structures and bonding
analysis of the complexes were examined by using the
LANL2DZ basis set and effective core potential (ECP) for
Mn atom, and the Pople6-311G* split-valence triple-ζ basis set
with polarization was used for Br− and other atoms.
The optimized ground-state geometric structures and
selected bond lengths of the complex 1·Mn-OH and their
deprotonated form are shown in Figure 9. As seen in the
optimized structures, the Mn−N bond lengths in 1·Mn-O−
(bond lengths 2.14 and 2.07 Å) are slightly longer than those
found in 1·Mn-OH (bond length 2.13 and 2.06 Å). The
elongation of the Mn−N bond is accompanied by the slight
shortening of the Mn−CO bonds in 1·Mn-O− (1.82, 1.80, and
1.80 Å) as compared to in 1·Mn-OH (1.83, 1.81, and 1.81 Å).
Further, HOMO−LUMO and TD-DFT calculations were
performed to get further insights. The calculated electronic
transitions with appropriate oscillator strengths were consid-
Scheme 3. Schematic Representation for the Allosteric
Regulation of CO Release
Figure 7. (A) Time-dependent UV−vis absorption spectra of 1·Mn-
O− (20 μM of 1·Mn-OH + 40 μM of (butyl)4N+F−) in CH3CN
solution during blue light irradiation (410 nm) from 0 to 4 min.Inset:
kinetic analysis of absorbance at 490 nm as a function of irradiation
time. (B) Colorimetric monitoring of CO release: 1·Mn-O− upon CO
release during irradiation with light.
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Figure 8. Amount of CO released (in ppm) by 1·Mn-OH in the
presence and absence of F− ion as a function of time during
irradiation with blue LED light (410 nm) in a closed desiccator.
Figure 10. Calculated HOMO−LUMO energy diagram of 1·Mn-OH
(ΔE = 2.78 eV) and 1·Mn-O− (ΔE = 1.69 eV). The most prominent
MOs involved with transitions (TDDFT) under the low-energy band
and their diagrams are shown.
increases efficient utilization of absorbed energy that increases
the CO photolabilty in 1·Mn-O−. Pradip K. Mascharak has
also described the role of electron-rich functionality on ligands
for the possible enhanced CO photolability.34
In addition, we have also constructed a molecular INHIBIT
logic gate using light and F− as an input in 1·Mn-OH.
INHIBIT logic gates are important logic functions used for the
construction of half-subtractor.35 Light and F− anion are
considered as two inputs, and the change in UV−vis
absorbance at 490 nm is examined as outputs. Only when
the input F− ion is present is the output signal ON or 1 state;
in all other cases the output signal is OFF or 0 state (Figure
11). The truth table reveals the necessary combinations of an
INHIBIT logic gate (Table 1).
Figure 9. Optimized ground-state geometric structures of the
complex (a) 1·Mn-OH and (b) their deprotonated form 1·Mn-O−.
ered, and those with energies falling within the range of the
lowest energy experimental absorption band 1·Mn-OH and 1·
Mn-O− are reported (Table S2). The calculated transitions
trend falls within the region of wavelengths observed
experimentally (Figure S16). The molecular orbital (MO)
energy diagram displays the compositions of the three lowest
occupied MOs and the LUMO of 1·Mn-OH and 1·Mn-O−
(Figure 10 and Figure S17).
CONCLUSION
■
In summary, we have reported an allosteric model Mn(I)
complex 1·Mn-OH by combining CO-releasing metal carbonyl
complex and an anion binding site phenol. In this allosteric
model, fluoride ion acts as an allosteric regulator. Complex 1·
Mn-OH represents an interesting new class of CO-releasing
The HOMO−LUMO gap of 1·Mn-O− (ΔE = 1.69 eV),
which is lesser than 1·Mn-OH (ΔE = 2.78 eV) agrees well with
the red-shift of the band from 412 to 490 nm upon
deprotonation; these results are in line with the experimental
observations. The smaller HOMO−LUMO energy gap (Figure
10) suggests that of 1·Mn-O− is more active upon photo-
irradiation. Therefore, we assume that as one goes from 1·Mn-
OH to 1·Mn-O− the conjugation is enhanced and the LUMO
level lowered. It is therefore evident that the alterations in the
energy of the HOMO and LUMO levels upon deprotonation
of the − OH group of terpy-phenol lead to enhanced CO
photolability.
From experimental and computational studies, it is
confirmed that the deprotonation of phenol in 1·Mn-OH
plays a major role in varying CO release behavior. We presume
that, the difference in CO release behavior may be due to (a)
red shifting the UV−vis band position along with an increasing
molar absorptivity coefficient, which effectively sensitizes the
light for fast CO release, and (b) increasing electron density on
terpy ligand by conversion of the phenol-to-phenolate anion
Figure 11. UV−vis spectra of 1·Mn-OH in the presence of two
inputs: light (410 nm) and F− anion (40 μM) in CH3CN.
F
DOI: 10.1021/acs.inorgchem.9b00984
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
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Table 1. Truth Table of the Molecular INHIBIT Gate with
the Inputs Light and F− Anion
Input
Light (410 nm)
Output
F− ion
Abs. at 490 nm (a.u.)
0
1
0
1
0
0
1
1
0 (0.041)
1 (0.310)
0 (0.032)
0 (0.039)
system that releases CO upon irradiation with light, and the
rate of CO release is allosterically regulated by fluoride anion.
The fast and slow release rate of CO from Mn(I) complexes
can be easily modulated by anion through deprotonation of the
phenol moiety. The CO release can be monitored through a
color change, fluorescence, and UV−vis absorption spectral
changes. We believe that the idea of allosteric regulation in CO
release may act as a new strategy for the development of new
CORMs, which will open a new vista in the field of gaseous
signaling molecule delivery.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.9b00984.
■
S
Experimental procedure, 1H NMR, HR-MS, UV−vis
studies, emission studies, CO release kinetics, FT-IR
studies, and computational data (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: amilanjoseNIT@nitkkr.ac.in.
■
ORCID
Rahul Sakla: 0000-0001-5538-1830
D. Amilan Jose: 0000-0003-2978-3400
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge NIT Kurukshetra, Haryana for the research
facilities. DAJ acknowledges the financial support of CSIR-
India for the CSIR-EMR(II) grant no 01(2855)/16. RS is
thankful to the financial support of DST, Haryana for HSCST
fellowship. We also acknowledge SAIF, Chandigarh, and IIT-
Ropar for providing 1H NMR, HR-Mass, ESI-Mass, and
CHNS(O) facilities on a charge basis.
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