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Squaramide macrocycles that prefer sulfate in water

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Meta-linked squaramide macrocycles bind SO42− so tightly in wet DMSO that NMR cannot measure Ka, and they still select sulfate in 50% water.

Source

Macrocyclic squaramides: anion receptors with high sulfate binding affinity and selectivity in aqueous media

Qin L, Hartley A, Turner P, et al. · Chemical science · 2016

doi.org/10.1039/c6sc01011cRead the full paper ↗62 citationscc by

Study at a glance

Design
Other — Synthesis and aqueous NMR titration of squaramide macrocycles for sulfate recognition
N
Anion-receptor binding study — no sample N
Population
Macrocyclic squaramide receptors in water/DMSO mixtures
Outcome
Sulfate binding affinity and selectivity versus competing anions

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Authors synthesized [2]- and [3]-squaramide macrocycles, titrated anions by 1H NMR in 0.5–50% water/DMSO, crystallized a 1:1 sulfate complex, and compared selectivity with chromate and with the sulfate-binding protein benchmark.

What they found

Meta receptors 1, 2, 5, and 6 are potent, selective sulfate ligands even in 50% water. 1 and 2 have Ka(SO42−) > 10^4 M−1; 2 is more sulfate-selective versus phosphate and acetate. The crystal shows a bowl/cone geometry with four NH···O hydrogen bonds. Receptor 6 discriminates sulfate from chromate better than the sulfate-binding protein.

The limits

What it doesn't show

Process-scale nuclear-waste extraction and clinical plasma sulfate assays are suggested applications, not demonstrated; some isomers are too insoluble for full Ka tables.

Key terms

Squaramide
Four-membered ring diamide that is a strong hydrogen-bond donor for anions.
MSQ
Macrocyclic squaramide receptor ([2] or [3] repeat).
Sulfate hydration penalty
ΔG ≈ −1090 kJ mol−1 makes aqueous sulfate recognition hard.
1:1 bowl complex
Crystal motif of 1·SO42− resembling a calixarene cone.
Selectivity ratio
Ka(sulfate)/Ka(competitor); for 6, Ka(sulfate) is at least 10^4 M−1.

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The preferred anion is:

Common questions

Which anion is preferred?

Sulfate, even in highly aqueous DMSO.

How tight is binding of 1 and 2 to sulfate?

Ka > 10^4 M−1, too high for accurate NMR.

What is the crystal geometry?

1:1 bowl/cone with C2v-like symmetry.

Why is aqueous sulfate hard?

Huge hydration energy (~−1090 kJ mol−1).

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