W4L16_Cation complexation in podands, corands and lariat ethers

Applications of Host-Guest Chemistry

Overview of Host-Guest Chemistry

• The discussion focuses on the applications of host-guest chemistry, specifically examining podands, corands, and spherands.

• Following this, the session will explore cyclodextrins and their host-guest behavior.

Understanding Podands

• A podand is defined as an organic molecule with an open chain conformation characterized by repeating units (n) and donor atoms (d).

• The open-chain structure allows for complexation but may lead to entropic penalties when encapsulating guest molecules.

Exploring Corands

• Corands are cyclic components derived from open-chain molecules, featuring donor atoms such as oxygen or nitrogen.

• When the donor atom is oxygen, these compounds are known as crown ethers; their properties will be discussed in detail later.

Cryptands: A More Rigid Structure

• Cryptands represent a more pre-organized and rigid structure compared to podands due to their bicyclic nature.

• They consist of bridging atoms (B), donor atoms (D), and multiple rings that create a three-dimensional configuration.

Specific Examples of Podands

• An example provided is pentaethylene glycol dimethyl ether, which has five ethylene glycol units in an open chain conformation.

• Encapsulation of a potassium cation requires conformational changes that result in entropy loss due to desolvation processes.

Modifying Podand Ligands for Better Encapsulation

• To improve encapsulation efficiency, bulky end groups can be introduced at the ends of podand ligands.

• Introducing quinoline moieties increases rigidity and facilitates binding with various cations like potassium or uranyl ions.

Benzoic Acid Substituted Podands

• Benzoic acid-substituted podands can effectively encapsulate cations through acidic hydrogen interactions when forming acetate or benzoate anions.

Crown Ethers: Recognition and Applications

Introduction to Crown Ethers

• Crown ethers gained recognition for their unique properties and applications; they were discovered by Charles Pedersen in 1987.

The Serendipitous Discovery of Crown Ethers

The Synthesis Process

• The discovery of crown ethers occurred accidentally while synthesizing an organic molecule, highlighting the role of serendipity in scientific breakthroughs.

• The synthesis involved sodium hydroxide and tertiary butanol, aiming to create a specific compound under particular workup conditions.

• A dihydroxy compound was formed where one OH group was protected; this led to nucleophilic attack and the formation of sodium chloride as a byproduct.

• Trace amounts of catechol in the starting material unexpectedly resulted in the production of Dibenzo-18-crown-6 during the reaction process.

Characteristics of Dibenzo-18-Crown-6

• The name "Dibenzo-18-crown-6" indicates its structure: an 18-membered ring with six etheric oxygen atoms and two phenyl rings, produced at only 0.4% yield.

• Despite being a minor product, Pedersen successfully isolated dibenzo-18-crown-6 and studied its properties, showcasing remarkable synthetic skills.

Solubility Properties

• Dibenzo-18-crown-6 is sparingly soluble in methanol but shows significantly enhanced solubility when mixed with alkali metal salts like potassium chloride.

• This unique property suggests that potassium cations fit into the cavity of the crown ether, enhancing solubility dramatically.

Cation Complexation Insights

• Pedersen proposed that potassium ions could fit into the central cavity of dibenzo-18-crown-6, which was later confirmed through crystal structure analysis.

• Oxygen lone pairs within the cavity are oriented to maximize interactions with cations, demonstrating effective encapsulation capabilities for potassium ions.

Size Specificity and Variations

• The size compatibility between cations and crown ethers is crucial; larger or smaller cations do not fit well within dibenzo's cavity leading to ineffective complexation.

Development of Other Crown Ethers

• Researchers have created various crown ethers by modifying donor atom numbers or structures (e.g., using dicyclohexyl groups), allowing accommodation for different sized cations.

• More rigid systems can be developed using cyclohexane due to stereochemical restrictions, enhancing conformational stability.

• Larger-sized crown ethers (e.g., 8 or 7 oxygen atoms systems) can accommodate larger cations like cesium or rubidium effectively.

• Smaller-sized crown ethers (e.g., 15-membered ring with five oxygen atoms), such as 15-crown-6, are tailored for smaller sodium cations due to their size requirements.

Dicyclohexyl Conformations and Binding Constants

Overview of Dicyclohexyl Configurations

• The dicyclohexyl system can exist in five distinct conformations: cis-syn-cis, cis-anti-cis, trans-syn-trans, trans-anti-trans, and cis-trans.

Comparison of Binding Constants

• The discussion transitions to comparing binding constants for different ligands, specifically podands and cyclic ethers (corands), in relation to metal cations.

Analysis of 18-Crown-6 vs. Pentaethylene Glycol

• A comparison is made between the binding efficiency of 18-crown-6 (a cyclic ether) and pentaethylene glycol (PEG), both having six donor atoms.

• For potassium ions, the log K value for 18-crown-6 is significantly higher at 6.08 compared to only 2.3 for PEG, indicating superior encapsulation efficiency.

Importance of Ligand Pre-Organization

• The high binding constant for 18-crown-6 is attributed to its pre-organized structure with converging binding sites that effectively encapsulate potassium ions.

Enhancing Binding Constants through Chemical Modification

Introduction to Lariat Ethers

• Scientists have synthesized lariat ethers by modifying cyclic structures; these contain four oxygen atoms and two nitrogen atoms with a log K value of 2.04 for potassium cations.

Modifying NH Groups to Increase Donor Atoms

• By replacing NH groups with NR groups containing additional donor atoms, the number of donor sites increases by two, enhancing binding potential.

Mechanism of Lariat Ether Functionality

• The flexible sidearm in lariat ethers acts like a lasso; upon interaction with potassium cations, it changes conformation to stabilize the ion through additional donor interactions.

Impact on Binding Constant Magnitude

Total Donor Atom Count and Stability Enhancement

• With modifications leading to eight total donor atoms interacting with potassium ions, this results in increased stability and an enhanced log K value rising to 4.8.

Significance of Structural Modifications

• These structural modifications demonstrate how altering ligand configurations can significantly improve binding constants beyond initial values.

Further Modifications: Bi-Bracchial Ethers

Definition and Structure of Bi-Bracchial Lariats

• Further enhancements involve bi-bracchial ethers where both NH groups are replaced by R groups; these compounds represent advanced modifications aimed at increasing ligand efficacy.