The Relevance of Size Matching in Self-assembly: Impact on Regio- and Chemoselective Cocrystallizations

Article abstract of DOI:10.1002/chem.202002264

Decamethonium diiodide is reported to perform the chemo- and regioselective encapsulation of para-dihalobenzenes through the competitive formation of halogen-bonded cocrystals starting from solutions that also contain ortho and meta isomers. Selective caging in the solid occurs even when an excess ortho or meta isomers, or even a mixture of them, is present in the solution. A prime matching between the size and shape of the dication and the formed dianions plays a key role in enabling the selective self-assembly, as proven by successful encapsulation of halogen-bond donors as weak as 1,4-dichlorobenzene and by the results of cocrystallization trials involving mismatching tectons. Encapsulated para-dihalobenzenes guest molecules can be removed quantitatively by heating the cocrystals under reduced pressure and be recovered as pure materials. The residual decamethonium diiodide can be recycled with no reduction in selectivity.

Full text of DOI:10.1002/chem.202002264

Accepted Article
Accepted Article
Title: The Relevance of Size Matching in Self-assembly: Impact in
Regio- and Chemoselective Cocrystallizations
Authors: Rong Cao and Giuseppe Resnati
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To be cited as: Chem. Eur. J. 10.1002/chem.202002264
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1/2020

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COMMUNICATION
The Relevance of Size Matching in Self-assembly: Impact in
Regio- and Chemoselective Cocrystallizations
Dedicate to Prof. Jane S. Murray on the Occasion of her 65th Birthday
Jing–Xiang Lin,a,b Andrea Daolio, Patrick Scilabra, Giancarlo Terraneo, Hongfan Li, Giuseppe
c
c
c
a
c,
a,
Resnati * and Rong Cao *
[a]
Dr. H. Li, Prof. R. Cao
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter; Chinese Academy of
Sciences;
Fuzhou 350002, P. R. China;
E-mail: rcao@fjirsm.ac.cn (R.C.)
[b]
Dr. J.-X. Lin
The School of Ocean Science and Biochemistry Engineering, Fujian Polytechnic Normal University (formerly called Fuqing
Branch of Fujian Normal University);
Fuqing, 350300, P. R. China;
[c]
Dr. A. Daolio, P. Scilabra, Prof. G. Terraneo, Prof. G. Resnati
NFMLab; Department of Chemistry, Materials and Chemical Engineering “Giulio Natta; Politecnico di Milano;
via Mancinelli 7; 20131 Milano, Italy;
E-mail: giuseppe.resnati@polimi.it (G.R).
3
4
Abstract: Decamethonium diiodide is reported to perform the or of neutral molecules by calixarenes and cyclodextrins begun
chemo- and regio-selective encapsulation of para-dihalobenzenes to be studied.
via competitive formation of halogen bonded cocrystals starting from
We decided to assess to what extent the effect of
solutions containing also ortho and meta isomers. Selective caging dimensional matching of interacting modules on self-assembly
5
in the solid occurs even when excess ortho and meta isomers, or a processes can be influential enough to enable the formation of
mixture of them, are present in solution. A prime matching between heteromeric adducts when the inter-components attractive
the size and shape of the dication and the formed dianions plays a interactions are weak, specifically as weak as the halogen bonds
key-role in enabling for the selective self-assembly, as proven by (HaBs)6 formed by unactivated chloro- and bromocarbons. We
successful encapsulation of halogen bond donors as weak as 1,4- proved the importance of size and shape matching of starting
dichlorobenzene and by the results of cocrystallization trials components in regioselective self-assembly processes and
involving mismatching tectons. Encapsulated para-dihalobenzenes investigated its hierarchical effectiveness relative to inter-
guest molecules can be removed quantitatively by heating the components interactions strength. Specifically, in this paper we
cocrystals under reduced pressure and be recovered as pure report that 1,4-dichloro- and 1,4-dibromobenzene (1a,b), two
materials. The residual decamethonium diiodide can be recycled weak
HaB
donors,7
self-assemble
diiodide
with
1,10-
with no selectivity reduction.
bis(trimethylammonium)decane
(decamethonium
diiodide, 2b) and afford the 1:1 cocrystals 1a∙2b and 1b∙2b
Scheme 1). In these adducts, the linear, trimeric and
supramolecular dianions I ∙∙∙X–C –X∙∙∙I are formed via long
and weak C–X∙∙∙I HaBs (X = Cl and Br). The dication length (viz.
(
Supramolecular chemistry deals with the recognition,
organization, and self-assembly of molecules into zero-, one-,
two-, or three-dimensional architectures. The engineering of
these processes poses tremendous challenges but offers
6
H
4
+
+
N –N separation) is similar to the supramolecular dianions
unprecedented opportunities for
a plethora of functional
properties.1 Supramolecular self-assembly is affected by both
energetic and geometric features. For instance, the
effectiveness and selectivity of a host material in coordinating
guest molecules depend on the balance between the strength of
host/guest interactions and the size and shape complementary
of the two modules. These two aspects and the importance of
their synergistic action for effective binding became apparent
since the early stages of supramolecular chemistry, when the
recognition of different cations by crown-ethers and kryptands2
Scheme 1. Structural formulas of used tectons.
1
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COMMUNICATION
length (viz. I ∙–I separations) and we suggest that this size
matching effect plays a major role in driving the self-assembly
processes. This hypothesis is confirmed by the fact that when
there is a size or shape mismatching between the dication of 2
and the supramolecular dianion given by 1, cocrystals are
formed only occasionally and only if the inter-component
interactions are strong. Out of fifty one attempted cocrystal
formations starting from mismatching modules, no cocrystal was
obtained starting from the p-, m-, and o-dichlorobenzenes 1a,d,g,
only one cocrystal from the corresponding dibromobenzenes
1b,e,h and five cocrystals from the three isomeric
diiodobenzenes 1c,f,i. These results and the formation of
halogen bonded cocrystals 1a∙2b and 1b∙2b from the weak HaB
donors 1a,b,7,8 prove here that a prime matching of the metrics
of interacting components can enable for the self-assembly of
components when the weak inter-component interactions fail in
driving the process. The practical relevance of the size matching
principle is demonstrated by its exploitation in isomer
separations via regioselective self-assembly processes.
Precisely, 1,4-dihalobenzenes 1a-c have been separated in
nearly quantitative yields from solutions containing the
respective 1,3- or 1,2-isomers 1d-i via regioselective cocrystal
formation with decamethonium diiodide 2b. Importantly, the
process occurs effectively also starting from mixtures containing
all the three isomeric dihalobenzenes and from mixtures wherein
the 1,4-isomer is a minor component (e.g., mixtures where the
p/o isomer ratio is 1:3).
Figure 1. Representation (Mercury 4.1.0) of the crystal structure of 1a∙2b. Top,
two different views of the confinement of a supramolecular dianion p-Cl
2
-
6 4
C H
·2I‾ in the space circumscribed by decamethonium dications. Bottom,
partial view of the crystal packing along c axis. HaBs are red dotted lines.
Color codes: White, hydrogen; grey, carbon; blue, nitrogen; green, chlorine;
violet, iodine.
The HaB donor ability of a halocarbon increases moving
from fluorine to iodine.7,8 Consistent with this trend, a Cambridge
Structural Database (CSD) search of crystals containing C
Br, and -I reveals that the percentage of entries wherein the
haloarene is halogen bonded is highest with C I and lowest
with Cl (Table S1). 1,4-Dihalobenzenes 1a-c behave
6 5
H -Cl,
-
6 5
H
6 5
C H
similarly and no adduct is found in the CSD for 1,4-
dichlorobenzene. A further confirmation of the weak HaB donor
ability of unactivated chlorobenzene derivatives comes from the
comparison of values of the surface electrostatic potential at the
halogen σ-hole (VS,max). σ-Holes with highly positive potentials
Figure 2. Representation (Mercury 4.1.0) of the superimposed crystal
structures of cocrystals 1a∙2b (green) 1b∙2b (brown) and 1c∙2b (purple).
Decamethonium dications and supramolecular dianions are in ball and stick
and space filling representation, respectively.Figure Caption.
are more likely to serve as strong HaB donors. VS,max is 5.3, 12.2,
1
-Cl, -Br, and -I, respectively,7a-c,9 and
and 17.3 kcal∙molˉ in C
H
6 5
Similar to other cocrystals where decamethonium diiodide,
and shorter or longer α, ω-dionium dihalides, encapsulate size
matching HaB donors,11 anions are fastened close to nitrogens
at the endings of the polymethylene chain by electrostatic
similar trends are shown by other halobenzenes (VS,max is 18.4,
1
2
7.2, and 35.9 kcal∙molˉ in the corresponding pentafluorinated
derivatives and 19.6 and 25.7 kcal∙molˉ1 in 1,4-Br
2
2
- and 1,4-I -
6 4
C H ).
+
attraction and N –C–H∙∙∙I ˉ hydrogen bonds (HB) (e.g., three
Despite their poor HaB donor ability, p-dichloro- and p-
dibromobenzene (1a,b) afford the cocrystals 1a∙2b and 1b∙2b in
HBs with an average length of 312.1 pm are present in 1a∙2b).
Iodides are thus conveniently spaced to pin dihalobenzenes
nearly quantitative yields and high purity (Figures 1 and S25) on 1a,b at either halogen atoms. Linear, trimeric, and
isothermal evaporation of chloroform/methanol solutions
supramolecular dianions I ∙∙∙X–C –X∙∙∙I are formed via long
containing equimolar amounts of decamethonium diiodide (2b) and weak C–X∙∙∙I HaBs (X = Cl and Br) (Table 1). The X∙∙∙I
and dihalobenzenes 1a,b. The homogeneity of obtained crystal
separations are 369.3(7), 359.2(4), and 352.2(5) pm in 1a∙2b,
batches was proven by powder X-ray diffraction patterns (PXRD) 1b∙2b, and 1c∙2b; the corresponding normalized contacts (N
)12
Figures S30 and S31). Single crystal X-ray analyses revealed
are 0.94, 0.90, and 0.85, respectively, confirming that HaBs are
that 1a,b∙2b are isostructural with 1c∙2b10 (Figure 2) despite the weaker in 1a∙2b than in 1c∙2b and have an intermediate
6
H
4
c
(
non-minor differences in the attractive intermolecular
interactions in the three cocrystals (Figure 3). This is consistent
with the fact that the size and shape matching of dication
molecules and dianions supramolecules has a major role in
driving the self-assembly and determining the cocrystal
architectures.
strength in 1b∙2b. Cocrystal 1a∙2b is the first adduct formed by a
dichlorobenzene (Table S1). Importantly, supramolecular
dianions
I
∙∙∙X–C
6
H
4
–X∙∙∙I
sit in their position within a
rectangular parallelepiped shaped cavity defined by four dication
+
+
molecules (Figures 1 and S25) and the N –N and I — I
separations are quite similar, their difference being at most 36
pm. Hirshfeld surfaces of para-dihalobenzene tectons in
2
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cocrystals 1a-c∙2b give an insight in the varying relevance of
different supramolecular interactions present in these
isostructural lattices (Figure 3). The faint red spots on the
extension of the C–Cl bonds in 1a correspond to the long and
weak C–Cl∙∙∙I HaBs in 1a∙2b and contrast with the intense red
spots on the elongation of C–I bonds in 1c (corresponding to
close and strong C–I∙∙∙I HaBs in 1c∙2b). Numerous hydrogen
+
bonds are also evidenced; for instance, the N –C–H∙∙∙I
Figure 3. Hirshfeld surface of p-dichloro-, p-dibromo- and p-diiodo-benzene
units in cocrystals 1a-c∙2b (left, middle and right, respectively).
interactions mentioned above.
Table 1. Selected structural parameters for cocrystal 1a-c∙2b.
The applicative usefulness of size and shape matching effect
in driving self-assembly processes is shown by the
regioselective adducts formation enabled by the greater affinity
of 2b for para-dihalobenzenes 1a-c than for meta and ortho
isomers 1d-i.
N+
N+
Cocrystal
Nc Value of
C – X ∙ ∙ ∙ I ̄
Angle (°)
Iˉ
Separation
pm)
—
Iˉ
—
X∙∙∙I ̄ HaB
Separation
(pm)
(
1a∙2b
1b∙2b
1c∙2b
0.94
0.90
0.85
178.49
179.64
179.96
1361.2
1373.6
1402.6
1397.3
1398.6
1402.3
Isothermal evaporation of chloroform/methanol solutions
containing equimolar amounts of 2b, 1a, and 1d, or of 2b, 1a,
and 1g affords the 1a∙2b adduct as pure crystalline material and
in nearly quantitative yields (Table S5, Figure S16), while the
dichlorobenzenes 1d and 1g remaining in solution. Analogously,
solutions containing 2b and the dibromobenzene isomers (i.e.,
solutions of 2b, 1b, and 1e, or of 2b, 1b, and 1h) afforded
exclusively cocrystal 1b∙2b (Figure S17), and solutions
containing 2b and the diiodobenzene isomers (i.e., solutions of
To systematically verify at what extent the size and shape
matching favors or determines self-assembly processes in the
absence of strong inter-component interactions, cocrystal
formation trials are performed starting from HaB donors and
acceptors with different steric and electronic features. Ortho-,
meta-, and para-dihalobenzenes 1a-i are used to assess the
effect of the size/shape of the trimeric dianions possibly formed
on self-assembly (linear vs. angled trimers formed from para vs.
ortho/meta isomers). Octa- and dodecamethonium diiodides 2a
and 2c are employed to evaluate the effect of N+ — N+
separations shorter and longer than that of 2b, and n-alkyl-
trimethylammonium iodides 2d-f are used as two units of these
ammonium salts are chemically and metrically equivalent to one
unit of diammonium salts 2a-c.
2b, 1c, and 1f, or of 2b, 1c, and 1i) afforded exclusively
cocrystal 1c∙2b (Figure. S20). Clearly, the selective cocrystal
formation enabled by size and shape matching between
decamethonium cation and supramolecular anions formed by p-
dihalobenzenes allows for quantitative, facile, and scalable
separation of regioisomeric dihalobenzenes. This is the case
also when crystallizations are performed from solutions
containing an excess of the mismatching isomer (e.g., a 1:3 ratio
between the matching and the mismatching dihalobenzenes
(Figures S18 and S19)).
+
+
As mentioned above, the N —N and I —I
separations
The results of all crystallization trials are summarized in
Tables S3 and S4. The eighteen trials involving dichlorobenzene
isomers 1a,d,g afford only the size matching cocrystal 1a∙2b, i.e.,
match in all three cocrystals 1a-c∙2b. Cocrystal formation from
solutions containing 2b and 1a, 1b, and 1c, may afford solid
solutions13 (wherein the 1a/1b/1c content is a function of the
C–Cl∙∙∙I
HaBs are not strong enough to entail cocrystal
respective concentration in solution). Alternatively, a single pure
cocrystal may be formed via chemoselective inclusion in the
adduct of the strongest HaB donor if the different strength of the
HaBs present in the pure cocrystals 1a-c∙2b is influential. Indeed,
formation in the absence of the size and shape matching of the
components. The eighteen trials involving dibromobenzenes
1b,e,h afford the matching cocrystal 1b∙2b and the mismatching
cocrystal 1b∙2c. In contrast, the eighteen trials involving
diiodobenzenes 1c,f,i afford the matching cocrystal 1c∙2b and
five mismatching cocrystals, namely 1f,i∙2b, 1f,i∙2c, and 1i∙2d.
Clearly, the C–I∙∙∙I HaBs formed by unactivated iodoaromatics
are strong enough to occasionally drive the formation of
heteromeric adducts also in the absence of the components size
matching. Single crystal X-ray analysis of 1b∙2c, 1f,i∙2b, and
1
c∙2b is formed from the four-tectons solution containing
equimolar amounts of 2b, 1a, 1b, and 1c and from the three-
tectons solutions (containing 2b, 1a, and 1c or 2b, 1b, and 1c)
while 1b∙2b is selectively formed from the three-tectons solution
containing 2b, 1a, and 1b (Table S6, Figures S21-S24).
In order to demonstrate the practical usefulness of regio-
and chemoselective cocrystallizations described above, the pure
1i∙2d (Tables S8 and S9; Figures S26-S29) was possible and
1
a-c∙2b cocrystals were heated under vacuum to remove
showed that mismatching modules result in crystal packings,
and sometimes even stoichiometries, different from size
matching cocrystals 1a-c∙2b.
dihalobenzene molecules namely to prove the potential of
decamethonium diiodide (2b) as a reusable agent for the
separation of mixtures of o-/m-/p-dihalobenzenes and of p-
dihalobenzenes
with
different
halogen
atoms.
Thermogravimetric analyses of 1a-c∙2b cocrystals (Figures S34-
S36) showed that the corresponding dihalobenzenes were
released (at ambient pressure) in quantitative yields. Gram scale
tests on 1a-c∙2b cocrystals revealed that the dihalobenzene
sublimation from the cocrystals was better performed under
3
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COMMUNICATION
reduced pressure (0.05 mmHg) and it was quantitative after ~10
hours at 160 °C for 1a and at 220 °C for 1b,c. The three
dihalobenzenes were recovered as highly pure and crystalline
materials on cooling the vapors, while the residual
decamethonium diiodide 2b was a whitish powder which could
be reused for selective cocrystal formation without further
purification and with no decrease in the efficiency and selectivity
of the self-assembly.
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Acknowledgements
We are grateful for financial support from the National Key R&D
Program of China (Grant No. 2017YFA0206800), the NSFC
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Keywords: halogen bond • cocrystallization • selectivity • size-
matching effect • supramolecular chemistry
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[
12]
c
N is defined as Dij/(rvdWi + rvdWj), where Dij is the experimental distance
between halogen atom i and nucleophilic atom j, and rvdwi/rvdWj are the
van der Waals radii of i/j; if j is an anion, rPj, the Pauling ionic radius of j,
substitutes for
vdWj c
r . N allows different interactions lengths to be
compared in a more reliable way than by using absolute separation
values. Ncs smaller than 1 correspond to attractive interactions and the
smaller Nc is, the stronger the interaction.
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Entry for the Table of Contents
Selective cocrystallization: Decamethonium diiodide demonstrate region- and chemoselective cocrystallization with para-
dihalobenzenes over its isomers thanks to the size/shape matching effect and hierarchical halogen bonds, which make it a promising
reagent for resolving dihalobenzene mixtures.
ORCID identification number(s) for the author(s) of this article:
Jing-Xiang Lin: 0000-0002-5519-4047
Andrea Daolio: 0000-0003-3571-3935
Patrick Scilabra: 0000-0003-1972-620X
Giancarlo Terraneo: 0000-0002-1225-2577
Giuseppe Resnati: 0000-0002-0797-9296
Rong Cao: 0000-0002-2398-399X
6
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