Supramolecular bidentate phosphine ligand scaffolds from deconstructed Hamilton receptors

Article abstract of DOI:10.1039/C6CC09198A

There is constant demand for new ligand archictectures on which inorganic and organometallic structures can be leveraged. An important, but often synthetically challenging, class of ligands is bidentate phosphines. Here we report self-assembling, supramolecular bidentate ligand scaffolds based on deconstructed Hamilton receptors with binding affinities up to 800 ± 100 M^-1

Full text of DOI:10.1039/C6CC09198A

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DOI: 10.1039/C6CC09198A
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Supramolecular Bidentate Phosphine Ligand Scaffolds from
Deconstructed Hamilton Receptors
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a
Daniel T. Seidenkranz, Jacqueline M. McGrath , Lev N. Zakharov, and Michael D. Pluth*
DOI: 10.1039/x0xx00000x
www.rsc.org/
There is constant demand for new ligand archictectures on which incorporation of non-covalent interactions in the ligand
inorganic and organometallic structures can be leveraged. An scaffold, such as hydrogen bonding and metal ligation.
important, but often synthetically challenging, class of ligands is However, few supramolecular approaches to bidentate ligand
bidentate phosphines. Here we report self-assembling, construction are based on self-assembling host-guest systems.
supramolecular bidentate ligand scaffolds based on deconstructed Moreover, a self-assembling ligand system that uses host-
-
1
Hamilton receptors with binding affinities up to 800  100 M .
guest interactions to control the magnitude of bidentate
character of monodentate ligands would enable precise tuning
of the shape and size of new metal-organic hybrid systems
based on host-guest binding affinities and guest
characteristics. Furthermore, control over typical bidentate
ligand parameters, such as bite angle, can be achieved through
the use of different host-guest combinations making this
approach amenable to combinatorial screening techniques.
Of the many host-guest architectures, the synthetic
New ligand architectures provide valuable platforms on
which inorganic and organometallic chemistry can be
supported, controlled, and leveraged for applications including
bioinorganic chemistry, materials science, and catalysis. Of the
numerous ligand platforms available, phosphine ligands are
1
among the most ubiquitous not only in chemical catalysis
,
but
also the construction of metal organic hybrid systems including
2-4
21
metal-organic frameworks,
complexes,
supramolecular coordination
and molecular capsules. Yet the design and
barbiturate receptor first synthesized by Hamilton lends itself
5, 6
7-9
22, 23
well to phosphine modification.
The receptor is
diversity of self-assembling architectures based on phosphine
ligands is frequently limited by challenging phosphine
derivatization. This drawback is particularly acute for the
characterized by six hydrogen bonds formed between the two
complimentary donor-acceptor-donor (DAD) and acceptor-
donor-acceptor (ADA) faces of the host and guest,
respectively. We envisioned that bifurcation of the ligand
scaffold would create a more flexible and accommodating host
pocket upon metal ligation, as well as allow for precise control
over the “bidentate” nature of the ligand through the use of
derivatized barbiturate guests. Additionally, coordination of
the ligands to the metal would provide the necessary pre-
organization required for guest binding, thus favoring
complete assembly of the supramolecular ligand structure
design and derivatization of bidentate phosphine ligands. To
combat these obstacles, researchers have begun to employ
10-14
supramolecular techniques in ligand design.
In addition to
creating large, meaningful ligand libraries from fewer
15, 16
components,
supramolecular ligand libraries are more
amenable to the implementation of high throughput screening
methodologies for identifying unique chemical structures,
reactivity, and materials with novel properties.
Supramolecular approaches to the construction of
functional bidentate ligands employ principles of molecular
recognition to develop ligands with compatible donor-acceptor
sites inherent in the ligand framework. Pioneering work by
(
Figure 1). This design strategy would generate a new class of
multicomponent self-assembled phosphine ligands that mimic
bidentate structures upon guest binding. Herein, we report the
design, synthesis, characterization, metal coordination, and
binding affinities of such self-assembled ligand scaffolds and
demonstrate that host-guest chemistry can be used to access
bidentate coordination motifs from simple, modular,
monodentate ligand components.
16-18
19, 20
Breit,
as well as van Leeuwen and Reek,
demonstrated
that functional bidentate ligands can be created through
a.
Department of Chemistry and Biochemistry, Materials Science Institute. University
of Oregon, Eugene, OR 97403. Email: pluth@uoregon.edu.
†
Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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Single crystals suitable for X-ray diffraction of all three
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DOI: 10.1039/C6CC09198A
isomers were grown from THF/pentane vapor diffusion under
an inert atmosphere (Figure S1). Notably, all regioisomers co-
crystallized with one molecule of THF, which was hydrogen
bonded to the proximal amide N-H and THF oxygen. The
preference for the hydrogen bond at the proximal amide is
likely due to the potential negative steric interactions between
the neopentyl group and the THF molecule. This observation is
in agreement with our hypothesis that bulky substituents
discourage host aggregation, but allow for guest inclusion.
To generate a host scaffold with two properly oriented
DAD faces to bind the incoming barbiturate guest, the ligands
must adopt a cis-geometry about the metal center. A common
method for determining ligand geometry is to use Pt(II) salts
Figure 1. Metal-assisted self-assembling of a bifurcated, phosphine
modified Hamilton receptor.
The effects of Hamilton receptor bifurcation and backbone
rigidity on guest binding have been previously reported and that form square planar complexes upon the addition of two
8
indicate that substitution at the distal amide and the rigidity of equivalents of ligand. These square planar, d Pt complexes
1
the backbone have significant effects on guest binding and display distinct J(
couplings constants for their cis- (>3000
Pt-P)
24
25
host aggregation. To encourage guest inclusion, while
limiting host aggregation, we hypothesized that neopentyl
substitution at the host distal amide would result in optimal
binding affinities. Moreover, we envisioned that the
regioisomerism of the appended phosphorus group in the
bifurcated receptor system would play a critical role in the
geometry and size of the host binding pocket. Specifically, we
hypothesized that the meta- substituted ligand would provide
the most pre-organized host pocket, but may be sterically
congested upon metal complexation. Therefore, the para-
substituted isomer could alleviate the steric congestion and
have minor effects on host pocket pre-organization. To
investigate these postulates, a suite of regioisomers containing
neopentyl substituted distal amides was synthesized according
to Scheme 1.
Hz) or trans- (< 3000 Hz) isomers. To investigate the
coordination properties of our ligand scaffold, Pt(II) complexes
4
b-c were prepared using one equivalent of [Cl Pt(COD)] with
2
two equivalents of the desired ligand in CH Cl (Figure 2a).
2
2
31
1
Following the complexation via P{ H} NMR spectroscopy
shows clean conversion upon the addition of ligand to the
Pt(COD)Cl (Figure 2b-c).
2
3
1
1
2 2
Figure 2. a) Synthesis of cis-PtL Cl complexes 4b-c. b) P{ H} NMR
3
1
1
(
2
202 MHz) of free 3b c) P{ H} NMR (202 MHz) of cis-PtL Cl2, 4b.
Scheme 1. Synthesis of phosphine ligands 3a-c.
1
Analysis of the J(
coupling constants confirms a cis-
Pt-P)
2
,6-Diaminopyridine was subjected to mono-amidation
conditions using 3,3-dimethylbutyryl chloride to give the
mono-substituted pyridine ( ), which was then used for
subsequent amidation of the ortho-, meta-, and para-
substituted iodobenzoyl chlorides to afford compounds 2a-c
geometry of both complexes with coupling constants of 3666
Hz and 3647 Hz for 4b and 4c, respectively. Attempts to
synthesize Pt complexes with ligand 3a, however, resulted in
the complete disappearance of a phosphorus resonance,
suggesting decomposition or possible formation of polymeric
1
,
respectively. Palladium-mediated couplings of HPPh and 2a-c species causing significant peak broadening. The inability to
2
in the presence of base resulted in the desired phosphine form discrete species with 3a is likely due to the steric
crowding about the metal center that would occur in a cis-
arrangement of the ligands.
ligands 3a-c in moderate to good yields. This highly modular,
three-step synthesis allows for fine control over the electronic
and steric parameters of the ligand scaffold through
substitution at both the phosphorus and diaminopyridine
backbone.
2
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To further study the ligand isomerism and host pocket experiments to accurately determine small chemical shift
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geometry, single crystals of 4b were grown from
THF/MeCN:pentane via vapor diffusion and analyzed by X-ray
diffraction. Analysis of the structure confirms the cis-
orientation about the Pt center (Figure 3). Interestingly, the
complex co-crystallizes with two molecules of THF, each bound
to a different phosphine ligand and amide. Consequently, the
structure adopts a dimeric motif with both intra- and
intermolecular hydrogen bonds. The intramolecular hydrogen
bonds occur between the proximal amide N-H of one
DOI: 10.1039/C6CC09198A
changes. Following the N-H resonance of the guest in a H O
2
saturated CDCl solvent system, a significant downfield shift is
3
observed with a measured association constant of 800
 100
-1
M (Figure 4). Switching to a more competitive solvent such as
MeCN resulted in attenuated, but measurable, binding
 5 M demonstrating the propensity of this
system to self-assemble even in a competitive hydrogen
bonding environment. Comparison between hosts 4b and 4c
-1
constant of 19
phosphine and the distal amide oxygen of the other revealed that para-substitution of the phosphorus group leads
phosphine, with a calculated distance of 2.922 Å, to effectively to a less pre-organized host pocket, indicated by the lower
-1
encapsulate the THF guests. The intermolecular hydrogen association constant of 260
 20 M . Taken together, these
bonds between the THF molecules and the upper and lower
amides have calculated distances of 2.947 Å and 2.811 Å,
respectively. The positioning of the host pocket cis to the
chloride ligands may help to explain the low association
constants (vida infra) as potential negative steric interactions
would occur between the chloride ligands and incoming guest.
Despite numerous attempts to crystalize the host-guest
binding data demonstrate that ligand coordination facilitates
barbiturate guest binding and that the geometry of the ligand
architecture can be used to tune guest binding fidelities.
complex 4b⊂5a, we were unable to obtain crystals suitable for
x-ray diffraction.
Figure 3. ORTEP representations of 4b with thermal ellipsoids drawn at
5
0% probability. Dimeric form of structure showing intra- and inter-
molecular hydrogen bonds with non-hydrogen bonding hydrogens
omitted for clarity.
1
Figure 4. Sample H NMR titration of 4b and 5a in H
2
O sat. CDCl
3
.
Previous work in our lab has shown that deconstructed
Hamilton receptors display 1:1 binding motifs, similar to the
original Hamilton receptor. The free rotation around the host
P-C bond, however, could allow for a 2:1 binding motif if the
enthalpic gain from hydrogen bond formation is greater than
the entropic cost of creating a three component system. To
In summary, we have developed a new supramolecular,
self-assembling ligand scaffold motif based on a deconstructed
Hamilton receptor. cis-PtL Cl host complexes that bind
24
2
2
synthetic barbiturate guests were synthesized and
characterized both in solution and the solid state. This
supramolecular system displays a 1:1 binding mode consistent
with a deconstructed Hamilton receptor, and guest binding
was observed in both competitive and non-competitive
solvents. The ease and high modularity of the host synthesis as
well as the guest tunability make this scaffold poised for
diverse applications ranging from acting as a building block for
larger self-assembled structures and materials as well as
applications in high-throughput and combinatorial screenings
of catalytic reactions.
confirm which binding motif was present, a Job plot for 4b and
1
5
a
was constructed using H NMR spectroscopy. Following the
chemical shift of the guest N-H resonance, the data support a
:1 binding motif as evidenced by a maximum in the Job plot
at 0.5 in H O sat. CDCl and 1% DMSO in CDCl (Figures S4 and
1
2
3
3
S6).
To assess the efficacy of our self-assembling ligand system,
1
H NMR titrations of host complex 4b and a synthetic
barbiturate 5a were performed and fit to a 1:1 model using the
This work was supported by NSF Grant CHE-1506221. The
NMR facilities at the UO are supported by the NSF (CHE-
26
Thordarson method. Due to solubility constraints of the
guest, inverse titrations (excess host with constant guest) were
0
923589, CHE-1427987), Oregon BEST, and ONAMI.
1
required to generate adequate signal in the H NMR
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DOI: 10.1039/C6CC09198A
The metal-assisted self-assembly of a phosphine-
modified, deconstructed Hamilton receptor is reported
as a new supramolecular ligand scaffold.
This journal is © The Royal Society of Chemistry 20xx
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