Unifying Evaluation of the Technical Performances of Iron-Tetra-amido Macrocyclic Ligand Oxidation Catalysts

Article abstract of DOI:10.1021/jacs.5b13087

The main features of iron-tetra-amido macrocyclic ligand complex (a sub-branch of TAML) catalysis of peroxide oxidations are rationalized by a two-step mechanism: Fe^III + H₂O₂ → Active catalyst (Ac) (k_I), and Ac + Substrate (S) → Fe^III + Product (k_II). TAML activators also undergo inactivation under catalytic conditions: Ac → Inactive catalyst (k_i). The recently developed relationship, ln(S₀/S_∞) = (k_II/k_i)[Fe^III]_tot, where S₀ and S_∞ are [S] at time t = 0 and ∞, respectively, gives access to k_i under any conditions. Analysis of the rate constants k_I, k_II, and k_i at the environmentally significant pH of 7 for a broad series of TAML activators has revealed a 6 orders of magnitude reactivity differential in both k_II and k_i and 3 orders differential in k_I. Linear free energy relationships linking k_II with k_i and k_I reveal that the reactivity toward substrates is related to the instability of the active TAML intermediates and suggest that the reactivity in all three processes derives from a common electronic origin. The reactivities of TAML activators and the horseradish peroxidase enzyme are critically compared.

Full text of DOI:10.1021/jacs.5b13087

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Communication
A Unifying Evaluation of the Technical
Performances of TAML Oxidation Catalysts
Matthew A DeNardo, Matthew Richard Mills, Alexander D Ryabov, and Terrence J. Collins
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b13087 • Publication Date (Web): 17 Feb 2016
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Chart 1. TAML activators employed (see Table 1 for X/R; Y is usually H O). TAML® is a registered
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Figure 1. LFER between log k
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Figure 2. LFER between log k
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Orange II dye.
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Figure 2S. Initial rate of 4-catalyzed bleaching of Orange II by hydrogen peroxide as a function of [H
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A Unifying Evaluation of the Technical Performances of TAML
Oxidation Catalysts
7
8
9
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Matthew A. DeNardo, Matthew R. Mills, Alexander D. Ryabov*, and Terrence J. Collins*
Department of Chemistry, Institute of Green Science, Mellon Institute, Carnegie Mellon University, Pittsburgh, Pennsylvania
15213
Supporting Information Placeholder
ABSTRACT: The main features of TAML catalysis of peroxide
each catalytic process. This study gives a unifying evaluation of
these rate constants for fifteen TAML activators over the
generational ligand structures 1⎼4. The results deliver the relative
reactivity powers and limitations within the members of this suite
of catalysts. Here we show that a remarkable preservation of the
III
oxidations are rationalized by the twoꢀstep mechanism: Fe
+
+
III
H O → Active catalyst (Ac) (k ), Ac + Substrate (S) → Fe
2
2
I
Product (k ). TAML activators also undergo inactivation under
II
catalytic conditions: Ac → Inactive catalyst (k ). The recently
i
ꢀ
ꢁ
ꢄ
ꢅꢅ
relationships between k , kII, and k persists across the discovered
I i
developed relationship, ln ꢀ
ꢃ
ꢇFeꢈꢈꢈꢉꢊꢋꢊ where S and S∞ are
0
ꢄ
ꢆ
ꢂ
millionꢀfold ranges in k and k and thousandꢀfold range in k for
II
i
I
[
S] at time t = 0 and ∞, respectively, gives access to k under any
i
all of the TAMLs studied.
conditions. Analysis of the rate constants k , k and k at the enviꢀ
I
II
i
ronmentally significant pH of 7 for a broad series of TAML actiꢀ
vators has revealed a sixꢀorders of magnitude reactivity differenꢀ
tial in both k and k and threeꢀorders differential in k . Linear free
Chart 1. TAML activators employed (see Table 1 for X/R;
Y is usually H O). TAML® is a registered trademark cov-
2
II
i
I
ering tetra-organic-amido-N macrocyclic ligand complex-
es.
energy relationships (LFERs) linking k with k and k reveal that
II
i
I
6
the reactivity towards substrates is related to the instability of the
active TAML intermediates and suggest that the reactivity in all
three processes derives from a common electronic origin. The
reactivities of TAML activators and the horseradish peroxidase
enzyme are critically compared.
Understanding the origins of lifetimeꢀcontrol in functional oxidaꢀ
1
tion enzyme mimics is as useful for furthering catalyst design as
it is for advancing sustainable chemical technologies. The iteraꢀ
tive design of the fully functional, small molecule peroxidase
enzyme mimics called TAML activators (Chart 1) has driven our
program for several decades. This has led to remarkably effective
and efficient catalysts for oxidations by hydrogen peroxide, a
prevalent reagent in both biochemistry and chemical
While the values of k and k can be obtained directly from kinetic
I
II
data, the determination of k is much more complicated—two
i
7
approaches have been developed. The earlier approach rests upon
2,3
technology. All TAML catalysts to date have been found to
ensuring a pure competition between substrate oxidation and cataꢀ
lyst inactivation requiring catalyst activation to be fast and subꢀ
strate oxidation to be rateꢀdetermining (i.e. k [H O ] >> k [S],
4
adopt the same stoichiometric mechanism in which the resting
ferric catalyst reacts with the primary oxidant (k ) to form the
I
I
2
2
II
catalytically active species (Ac), which then either oxidizes a
Scheme 1). This reactivity regime is generally found for peroxiꢀ
substrate (k ) to regenerate the resting catalyst or undergoes inacꢀ
4
II
dase enzymes. However, it can rarely be enforced for synthetic
tivation (k ) (Scheme 1, where k , associated with the reverse of
i
ꢀI
oxidation catalysts because catalyst activation (k ) is usually rate
I
5
peroxide activation, is kinetically negligible and all rate constants
determining instead. Fortunately, for TAML activators, the reꢀ
k , k and k are pH dependent).
I
II
i
gime can be imposed, allowing k to be captured, by setting the
i
For TAML activators, the magnitudes of the second order rate
experimental conditions: (i) pH > 10, (ii) high [H O ], (iii) low
[S], and (iv) slowꢀreacting S.
2
2
7
constants, k and k , that describe the catalytic activity, together
I
II
with the first order inactivation rate constant k that characterizes
i
the lifetime, determine the comparative technical performance in
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Table 1. Rate constants k , k and k for TAMLs 1-4 (Chart
I
II
i
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-1 -1
-1
1
) at pH 7 and 25 °C (k and k are in M s , k is in s ).
I II i
ꢀ4
3
a
TAML X /X /R
kI
10 ×k
II
10 ×ki
1
2
1
a
H/H/Et
NH /H/Me
H/H/Me
CO
Me/Me/Me
1.8±0.1
28±2
0.28±0.01
0.42±0.02
0.09±0.01
1.15±0.07
0.30±0.01
0.11±0.01
0.42±0.01
0.34±0.02
1.1±0.3
1b
2
1
1
1
1
c
d
e
f
31.4±0.1
0.495±0.002
0.73±0.01
0.90±0.05
2.7±0.2
4.1±0.1
12±1
Scheme 1. General mechanism of TAML activator
catalysis adopted for mathematical treatment.
Me/H/Me 38±1
2
0
1
2
3
4
5
6
7
8
9
0
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2
3
4
5
6
7
8
9
0
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2
3
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5
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7
8
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0
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2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
49±3
NO
NO
/H/Me
/H/F
152±5
350±2
361±1
1490±20
1850±90
2
1g
1h
2
This reactivity regime is often unattainable at pH 7 (k [H O ] >>
I
2
2
kII[S] does not hold), which is by far the most important pH for
understanding the relative catalytic behavior. This is because
TAML catalysts enable, inter alia, the high performance mitigaꢀ
Cl/Cl/F
2.50±0.03
11.0±0.4
20±1
2
a
Cl/Cl/Me
CN/H/Me
4.0±0.2
26±1
2b
2c
tion of micropollutants in water where practical considerations
8ꢀ17
require the pH to be near neutral.
Nevertheless, by setting the
NO /H/Me
1900±100 52±7
85±6
2
above conditions at higher pH, the analytic expression
b
3
a
H/H/Ph
H/H/Me
85±3
0.19±0.01
0.23±0.05
3.0±0.4
ln(ln[S /S ]) = ln(k [Fe] /k ) – k t can be employed to determine
t
∞
II
tot
i
i
b
3b
140±20
1500±30
2.3±0.2
6.8±0.7
k (where S and S are substrate concentrations at time t and t=∞,
i
t
∞
III
b
respectively, and [Fe ] is the total catalyst concentration). It
3c
4
NO /H/Me
2.2±0.3
tot
2
follows that the condition, S > 0, must hold for the analysis to be
ꢀ4
ꢀ4
∞
⎼/⎼/Me
0.63±0.02 (1.19±0.03)×10 (4.1±0.1)×10
applicable. This is easily achieved by resorting to low catalyst
loadings.
a
b
All k
values determined using eq 4. Rate constants for 3 have
i
19
1
8
been published.
In order to assess k at pH 7, a second approach was devised.
A
i
system of three differential equations (eqs 1ꢀ3) was developed to
permit the treatment of the three rate constants in a single kinetic
analysis where there is no analytic solution. Therefore, mathematꢀ
ical and chemical teams collaborated to develop a procedure that,
For many years, the azo dye Orange II has served us as a referꢀ
ence substrate for kinetic analyses. The pH 7 rate constants k and
I
kII were obtained by measuring the initial rates of bleaching of
Orange II by H O in the presence of 1⎼4 as described
remarkably, requires minimal data for evaluating k and applies
i
1
8
2
2
under all conditions. The important expression, eq 4, indicates
5,7,20ꢀ22
elsewhere.
The lifetimes of TAML activators are known to
that the amount of unreacted substrate (S ) is a function of the
17
∞
be influenced by [H O ]. This was first noted a decade ago,
confirmed quantitatively and then exploited practically by
generating H O2 enzymatically in situ. Therefore effective ki
2
2
rate constants k and k , as well as the total catalyst concentration
7
II
i
III
([Fe ] ). The elusive k can thus be evaluated provided the
23
tot
i
18
2
oxidant is used in excess and the precise value of k is known.
II
values were determined in the presence of a low constant [H O ]
2
2
Note that S does not depend on k .
∞
I
ꢀ3
of 2.5×10 M. All k values were calculated using eq 4, where S
i
∞
ꢀ
8
ꢀ9
>
0 was achieved by using very low [TAML] (ca. 10 , 10 and
10 M for 1, 2 and 4, respectively). Importantly, in the test case of
ꢍꢎꢏꢐꢅꢅꢅ
ꢍꢒ
ꢑ
ꢀ7
ꢈꢈꢈ
ꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌ
ꢃ ꢓꢔ ꢇFe ꢉꢇH O ꢉ ꢖꢌꢔ ꢇAcꢉꢇSꢉ
(1)
(2)
(3)
(4)
ꢈ
ꢕ
ꢕ
ꢈꢈ
1
c, the k at pH 7 depend very weakly on [1c] (Figure 1S of the
i
ꢍꢇꢗꢘꢉ
7
ꢈꢈꢈ
ꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌ ꢍꢒ ꢌꢃꢌꢔ ꢇFe ꢉꢌ–ꢌꢔ ꢇAcꢉꢇSꢉꢌ–ꢌꢔ ꢇAcꢉ
Supporting Information (SI)), as was found at pH 11. Projecting
reasonably to the entire suite, these inactivation processes are
unimolecular in catalyst under the specified conditions. The kinetꢀ
ic information is presented in Table 1 and useful relationships
derived therefrom are shown graphically in Figures 1 and 2. The
synthesis, characterization and catalytic evaluation of the new
TAML activator 4 are described in SI. This body of work allows
us to make the following conclusions concerning TAML activator
catalyzed oxidations at pH 7.
ꢈ
ꢈꢈ
ꢙ
ꢍꢇꢀꢉ
ꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌ ꢍꢒ ꢌꢃꢌ– ꢔ ꢇAcꢉꢇSꢉ
ꢈꢈ
ꢀ
ꢁ
ꢄ
ꢅꢅ
ꢇFeꢈꢈꢈꢉꢊꢋꢊ
ꢄ
ꢆ
ꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌꢌln ꢀ
ꢃ
ꢂ
By adding eq 4 to standard kinetic tools, we have been able to
determine the values of the effective rate constants k , k and k for
I
II
i
15 TAML catalysts that vary widely in ligand structure and
reactivity (Chart 1 and Table 1). The substrateꢀindependent kI
values can be of great utility to any researcher using TAML actiꢀ
vators at pH 7 as they will usually dictate the rate of substrate
oxidation and are available for assessing k values when k [H O ]
First, the line in Figure 1 establishes the rule for this TAML class
that, at neutral pH, higher catalytic activity (kII) is accompanied
by lower operational stability (k ), even over the diverse range of
i
structural motifs and reactivities of 1-4. This trend agrees with the
II
I
2
2
≈
kII[S].
general observation that catalysts displaying increased reactivity
1
are more prone to inactivation. Equation 5 provides an analytical
expression for the straight line of Figure 1 giving a slope of apꢀ
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proximately 1. Under these conditions, faster reacting TAML
nal diethyl substituted carbon in the sixꢀmembered tail ring in
place of geminal dimethylꢀ or difluoroꢀsubstitution patterns.
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catalysts will not do a great deal more work over time because the
degradation rates track the substrate oxidation rates closely. Thus,
factors that enhance the aggressiveness of TAML activators with
respect to target molecules decrease their operational stability.
The approximately linear trend lines of Figures 1 and 2 are conꢀ
sistent with the Lewis acidity at iron playing an important role in
all three processes. Following this rationalization, it is noteworꢀ
thy that the peroxide activation process (an oxidation at iron) is
accelerated by increased Lewis acidity at iron, which could seem
counterintuitive. We have long interpreted this feature as evidence
for heterolysis of the peroxide O–O bond, as this would be faster
with increasing acidity of the coordinated water and, especially,
logk = (0.9±0.1) × logk ⎼ꢌ(6.7±0.4)
(5)
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II
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28,29
the H O ligands.
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logk = (0.7±0.1) × logk ⎼ꢌ(0.8±0.5)
(6)
I
II
Figure 1. LFER between log k and log k of TAML activators at
i
II
25 °C and pH 7: k refers to the bleaching of Orange II dye.
II
The slope being near 1 in Figure 1 supports the hypothesis of
Scheme 1 that a common intermediate, Ac, participates in both
the k and k processes. As for the exact nature of Ac, very reacꢀ
II
i
Figure 2. LFER between log k and log k of TAML activators at
I
II
tive iron(V)oxo species have been characterized for various
2
4ꢀ26
25 °C and pH 7: k refers to the bleaching of Orange II dye.
II
TAML activators in organic solvents.
We have to date been
unable to observe or capture such species in aqueous H O sysꢀ
2
2
It is interesting to consider the relative rate behavior of TAML
activators and peroxidase enzymes as catalysts for peroxide oxiꢀ
dation of organic substrates in water. For the enzymes, catalyst
activation is fast, i.e. k >> k . For TAML activators, catalyst actiꢀ
tems. In electron transfer processes, which are among the possible
5
pathways for subject bleaching of Orange II, the kinetics in water
is dominated by iron(IV) species which are likely formed by fast
reduction of iron(V)oxo primary intermediates. Iron(IV) intermeꢀ
diates, the exact speciation of which depends on pH, have been
I
II
vation is typically rate limiting (k << k ), as is the case with Orꢀ
I
II
3
0
ange II. The small, 44,000 Da horseradish peroxidase (HRP) is
among the fastest activators of peroxide in the peroxidase family
with k = 2×10 M s . By comparison, at pH 7 2c has the highꢀ
implicated in TAML/H O catalytic oxidation of one electron
2
2
2
7
7
ꢀ1 ꢀ1 31
transfer agents.
I
3
ꢀ1 ꢀ1
Both rate constants kII and k vary remarkably by six orders of
est TAML k
value of (1.9±0.1)×10 M s . This leads to a cataꢀ
I
i
magnitude. The new generation TAML activator 4 (first reported
herein) is particularly valuable for this broad study as it extends kII
lyst design question—can the iterative design protocol that led to
2,3
TAML activators be extended to give new catalysts with k
I
and k by three orders of magnitude to anchor and improve confiꢀ
increased by four orders of magnitude to rival HRP? One can
foresee what this challenge might entail from the proportionality
i
dence in the observed trend, although it is markedly less active
than earlier generations represented by 1-3 (Table 1, Figure 1).
between k and kII. Based on eq 6, if kII for the oxidation of Orꢀ
I
For 4 at pH 7, the rate constants k and kII are almost identical.
ange II (25 °C and pH 7) could be increased in a future TAML
I
10
ꢀ1 ꢀ1 32
However at pH 11, 4 conforms to the general relationship k < k
activator to the diffusion controlled limit (kII ~ 10
corresponding k
I
M
s ), the
value would be ~10 M s . If this challenge
seems forbidding, consider that the 2c k value of 2c is ca. two
I
II
6
ꢀ1 ꢀ1
that holds for all other TAML activators with k and k of 660±10
I
II
3
ꢀ1 ꢀ1
and (7.5±0.3)×10 M s , respectively.
I
orders of magnitude greater than that of the prototype 1c and more
than three orders of magnitude greater than that of the least active
Second, the activation of peroxide (k ) is proportional to the oxiꢀ
I
dation of substrate (k ) and the data shown in Figure 2 can be
II
4
. The data in Figure 2 provide additional insight into the design
of this more ideal TAML. Replacement of the geminal ethyls of
a with methyls in 1c produces an increase in k relative to k
fitted by the linear analytical expression of eq 6. Since the point
for 1a deviates from the trendꢀline by greater than one order of
magnitude (the sole case of steric modulation), the data for this
catalyst was excluded from the fit—1a uniquely contains a gemiꢀ
1
I
II
indicating that steric bulk in this location hinders the H O activaꢀ
2
2
tion pathway. A design venture to further improve the kinetic rate
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Page 12 of 15
constants of TAML activators relative to the peroxidase enzymes
(5) Chahbane, N.; Popescu, D.ꢀL.; Mitchell, D. A.; Chanda, A.;
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Lenoir, D.; Ryabov, A. D.; Schramm, K.ꢀW.; Collins, T. J. Green
Chem. 2007, 9, 49ꢀ57.
is academically enticing. However, in comparing the utility of
TAML activators and peroxidases, it is important to recognize
that a typical TAML activator enjoys a large advantage in terms
of atom economy, comprising ~1% the mass of HRP, a particularꢀ
(
6) Collins, T. J.; GordonꢀWylie, S. W.; Horwitz, C. P. 2000,
30
U.S. 5,847,120.
ly light peroxidase enzyme.
Third, since both catalyst inactivation (k ) and the activation of
(7) Chanda, A.; Ryabov, A. D.; Mondal, S.; Alexandrova, L.;
Ghosh, A.; HangunꢀBalkir, Y.; Horwitz, C. P.; Collins, T. J. Chem.
Eur. J. 2006, 12, 9336ꢀ9345.
i
peroxide (k ) vary directly with substrate oxidation (k ), k and k
I
I
II
i
are also directly proportional. Again, at neutral pH catalyst activaꢀ
tion is typically rate determining in TAML processes. Here too,
activators capable of greater overall rates of substrate oxidation
controlled by the catalyst activation step display proportionally
increased rates of inactivation providing further evidence that all
three proportionalities derive from a common electronic origin.
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(
8) Mills, M. R.; AriasꢀSalazar, K.; Baynes, A.; Shen, L. Q.;
Churchley, J.; Beresford, N.; Gayathri, C.; Gil, R. R.; Kanda, R.;
Jobling, S.; Collins, T. J. Scientific Reports 2015, 5, 10511.
(
9) Kundu, S.; Chanda, A.; Thompson, J. V. K.; Diabes, G.;
In conclusion, this general evaluation of peroxide oxidation proꢀ
cesses delivers considerable insight into how TAML catalysis
works. The study exemplifies the wellꢀestablished approach of
using knowledge of the key rate constants, k , k and k here, that
Khetan, S. K.; Ryabov, A. D.; Collins, T. J. Catal. Sci. Technol. 2015,
5, 1775ꢀ1782.
(10) Kundu, S.; Chanda, A.; Khetan, S. K.; Ryabov, A. D.;
Collins, T. J. Env. Sci. Technol. 2013, 47, 5319ꢀ5326.
I
II
i
we call “technical performance parameters”, to generate robust
LFER analyses that give valuable insight into the forces underlyꢀ
ing each while bolstering the limited literature of catalyst inactivaꢀ
(
11) Kundu, S.; Chanda, A.; EspinosaꢀMarvan, L.; Khetan, S.
1
K.; Collins, T. J. Catal. Sci. Technol. 2012, 2, 1165ꢀ1172.
tion. In principle, this approach could have wider utility for probꢀ
ing the reactivity of other synthetic catalysts in oxidation, reducꢀ
tion or other processes.
(
12) Shen, L. Q.; Beach, E. S.; Xiang, Y.; Tshudy, D. J.; Khaniꢀ
na, N.; Horwitz, C. P.; Bier, M. E.; Collins, T. J. Env. Sci. Technol.
011, 45, 7882ꢀ7887.
2
ASSOCIATED CONTENT
(
13) Beach, E. S.; Malecky, R. T.; Gil, R. R.; Horwitz, C. P.;
Supporting Information is available free of charge on the ACS
publications website at http://pubs.acs.org.
Collins, T. J. Catal. Sci. Technol. 2011, 1, 437ꢀ443.
(14) Beach, E. S.; Duran, J. L.; Horwitz, C. P.; Collins, T. J.
Ind. Eng. Chem. Res. 2009, 48, 7072ꢀ7076.
Synthesis of 4; details of kinetic data collection.
AUTHOR INFORMATION
(
15) Chanda, A.; Khetan, S. K.; Banerjee, D.; Ghosh, A.; Colꢀ
lins, T. J. J. Am. Chem. Soc. 2006, 128, 12058ꢀ12059.
Corresponding Authors
(
16) Banerjee, D.; Markley, A. L.; Yano, T.; Ghosh, A.; Berget,
tc1u@andrew.cmu.edu; ryabov@andrew.cmu.edu
P. B.; Minkley, E. G.; Khetan, S. K.; Collins, T. J. Angew. Chem. Int.
Ed. 2006, 45, 3974ꢀ3977.
Notes
The authors declare no competing financial interests.
(17) Gupta, S. S.; Stadler, M.; Noser, C. A.; Ghosh, A.; Steinꢀ
hoff, B.; Lenoir, D.; Horwitz, C. P.; Schramm, K.ꢀW.; Collins, T. J.
Science 2002, 296, 326ꢀ328.
ACKNOWLEDGMENTS
TJC thanks the Heinz Endowments for funding. MRM is a CMU
(18) Emelianenko, M.; Torrejon, D.; Denardo, M. A.; Ryabov,
A. D.; Collins, T. J. J. Math. Chem. 2014, 52, 1460ꢀ1476.
1
Presidential Fellow. The H NMR spectrometers of the Departꢀ
ment of Chemistry NMR Facility were purchased in part with
funds from the NSF (CHEꢀ0130903).
(
19) Warner, G. R.; Mills, M. R.; Enslin, C.; Pattanayak, S.;
Panda, C.; Panda, T. K.; Gupta, S. S.; Ryabov, A. D.; Collins, T. J.
Chem. Eur. J. 2015, 21, 6226ꢀ6233.
REFERENCES
(
20) Ellis, W. C.; Tran, C. T.; Denardo, M. A.; Fischer, A.;
Ryabov, A. D.; Collins, T. J. J. Am. Chem. Soc. 2009, 131, 18052ꢀ
8053.
(1) Crabtree, R. H. Chem. Rev. 2015, 115, 127ꢀ150.
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2) Collins, T. J. Acc. Chem. Res. 1994, 27, 279ꢀ85.
3) Collins, T. J. Acc. Chem. Res. 2002, 35, 782ꢀ790.
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21) Popescu, D.ꢀL.; Chanda, A.; Stadler, M. J.; Mondal, S.;
Tehranchi, J.; Ryabov, A. D.; Collins, T. J. J. Am. Chem. Soc. 2008,
130, 12260ꢀ12261.
4
71ꢀ521.
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(
22) Ellis, W. C.; Tran, C. T.; Roy, R.; Rusten, M.; Fischer, A.;
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Ryabov, A. D.; Blumberg, B.; Collins, T. J. J. Am. Chem. Soc. 2010,
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23) Miller, J. A.; Alexander, L.; Mori, D. I.; Ryabov, A. D.;
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(
24) Tiago de Oliveira, F.; Chanda, A.; Banerjee, D.; Shan, X.;
Mondal, S.; Que, L., Jr.; Bominaar, E. L.; Münck, E.; Collins, T. J.
Science 2007, 315, 835ꢀ838.
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M. P.; Collins, T. J.; Dhar, B. B.; Sen Gupta, S. J. Am. Chem. Soc.
014, 136, 9524ꢀ9527.
2
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26) Ren, Q.; Guo, Y.; Mills, M. R.; Ryabov, A. D.; Collins, T.
J. Eur. J. Inorg. Chem. 2015, 2015, 1445ꢀ1452.
(27) Kundu, S.; Annavajhala, M.; Kurnikov, I. V.; Ryabov, A.
D.; Collins, T. J. Chem. Eur. J. 2012, 18, 10244ꢀ10249.
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28) Ghosh, A.; Mitchell, D. A.; Chanda, A.; Ryabov, A. D.;
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B. Can. J. Biochem. 1975, 53, 495ꢀ501.
(
32) Espenson, J. H. Chemical Kinetics and Reaction Mecha-
nisms; 2 ed.; McGrawꢀHill, Inc.: New York, 1995.
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Scheme 1S. Synthetic route for novel TAML activator 4.
2
32x121mm (120 x 120 DPI)
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