18-Crown-6: Applications in Coordinated Metal Halides and Effect on Oxytocin Stability

General Description

18-Crown-6 plays a crucial role in both the enhancement of luminescent properties and nonlinear optical effects in metal halide coordination compounds, including ZnX2(18-Crown-6) and Mn-based complexes. It demonstrates remarkable quantum yields and unique optical properties, influencing electronic interactions within these complexes. Besides, 18-Crown-6 significantly impacts the stability of oxytocin in aqueous buffers, acting as a stabilizer or destabilizer depending on the buffer composition and pH. 

Figure 1. 18-Crown-6

Applications in Coordinated Metal Halides¹

Crown ethers, discovered by Pedersen, are known as unique ligands in regard of many aspects. Today, they are available with different ring-opening diameters (e.g., 120−150 pm for 12-crown-4, 450−500 pm for 24-crown-8), and they can contain different heteroatoms such as oxygen, sulfur, or nitrogen as coordinating sites. In inorganic and metal−organic chemistry, crown ethers are known to coordinate almost all types of metal cations. Because of their strong chelating effect and adaptable ring-openings, even alkali metal cations can be strongly bound. Moreover, fascinating compounds were realized with crown ethers as ligands, including, for instance, alkali metal alkalides and electrides, phase-transfer reagents, or low-coordinated nitrogen complexes. 18-Crown-6 is perhaps the most widely applied crown ether. Because of its ring-opening diameter (∼300 pm), 18-crown-6 is especially known for optimal coordination of K + (r:138 pm).

In one study by Claus Feldmann's team, the crown-ether coordination compounds ZnX2 (18-crown-6) and EuX2(18-crown-6) (X: Cl, Br, I) as well as Mn 3Cl6 (18-crown-6) 2, Mn 3I 6(18-crown-6) 2, MnI 2(18-crown-6), and Mn 2I 4(18-crown-6) were prepared by ionic-liquid-based synthesis. The structural features of the title compounds are primarily influenced by the size of the cation in relation to the ring-opening of 18-crown-6 (about 300 pm). In this regard, Mn2+ (r: 83 pm) is neither small enough to clearly prefer off-center (3 + 3) coordination (like Zn 2+ , r: 74 pm) nor large enough for central coordination (like Eu2+ , r: 117 pm).

As a result, Mn3Cl 6(18-crown-6) 2, Mn3 I6 (18-crown-6) 2, and Mn 2I 4(18-crown-6) exhibit unusual single MnX4 tetrahedra coordinated to the crown-ether complex. The structural features of the crown-ether coordination compounds also have major impact on the optical properties. First of all, unexpected emission of all Zn 2+ -containing compounds was observed and could be attributed by computation to charge-transfer transition between the halide np orbital and the zinc 4s orbital. Besides the surprising PL as such, ZnI2 (18-crown-6) shows a remarkable quantum yield of 54%, which is the highest value observed for Zn2+ -based PL. The Mn 2+ - and Eu 2+ -containing crown-ether coordination compounds show bright PL with the characteristic d−d (Mn2+ ) and f−d transitions (Eu 2+ ). Surprisingly, the PL efficiency of Mn 3Cl 6(18-crown-6) 2, Mn3I 6 (18-crown-6)2 , and Mn 2I 4(18-crown-6) even outperform long-optimized commercial phosphors with unprecedented quantum yields of 82, 98, and 100% at ambient temperature. This excellent PL performance can be directly correlated to the structural features of the respective compounds. Besides bright PL, Mn 2I 4 (18-crown-6) shows an anisotropic angle-dependent emission under polarized light and a second-order nonlinear optical effect, which can be again related to its structural features with finite, noninversion symmetric sensitizer−activator Mn 2+−Mn 2+ couples and the presence of a polar, chiral space-group symmetry (P2 12 1 2 1). Such optical properties with bright emission, quantum yields near unity, and NLO effects (including polarized emission, SHG, and visible emission via SHG-driven excitation) are surprising and observed for the first time.

Effect on Oxytocin Stability²

Oxytocin is a nonapeptidic hormone, often used as a drug to combat postpartum hemorrhage, the primary cause of maternal deaths around the globe. Oxytocin also has other numerous biological and psychological functions including a role in lactation and relationships. Additionally, efforts have been made toward using oxytocin as a drug to treat conditions such as alcoholism, autism, and schizophrenia. Unfortunately, oxytocin, in aqueous solutions, degrades rapidly when kept at temperatures above 30 °C. Methods for enhancing oxytocin’s shelf life would therefore be beneficial.

The study found that while 12-crown-4 and 15-crown-5 do not stabilize oxytocin, 18-crown-6 does have a stabilizing effect in citrate/phosphate buffer at pH 4.5. However, in acetate buffer at the same pH, the presence of 18-crown-6 had a destabilizing effect, possibly leading to a different degradation pathway. Both the stabilizing and destabilizing effects, depending on the buffer used, are concentration dependent where a higher concentration of 18-crown-6 is linked to a stronger effect. It is hypothesized that this effect may be linked to 18-crown-6 binding to the protonated ammonium group of oxytocin. Ultraviolet and nuclear magnetic resonance spectroscopy experiments also showed that the presence of 18-crown-6 has an observable effect on the resulting oxytocin spectra.

Reference

1. Merzlyakova E, Wolf S, Lebedkin S, et al. 18-Crown-6 Coordinated Metal Halides with Bright Luminescence and Nonlinear Optical Effects. J Am Chem Soc. 2021; 143(2): 798-804.

2. Ghasemisarabbadieh M, Gizurarson S, Sveinbjornsson BR. Effect of 18-Crown-6 on Oxytocin Stability in Aqueous Buffer Solutions. ACS Omega. 2021; 6(8): 5805-5811.