Related Experiment Video
Updated: Apr 18, 2026
06:44
From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding
Published on: March 24, 2018
69.8K
Geminal dihalogen isosteric replacement in hydrated AI-2 affords potent quorum sensing modulators
Min Guo1, Yue Zheng, Jessica L Terell
1Department of Chemistry and Biochemistry, University of Maryland College Park, 20742, USA. hsintim@umd.edu.
Chemical Communications (Cambridge, England)
|January 10, 2015
Summary
Geminal dihalogens can mimic hydrated carbonyl groups in molecular interactions. This finding suggests novel strategies for designing ligands by utilizing halogen bonding as an alternative to hydrogen bonding.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Structural Biology
Background:
- Quorum sensing (QS) regulates bacterial communication and virulence.
- Autoinducer-2 (AI-2) is a common QS signal molecule.
- The transcriptional regulator LsrR controls AI-2 metabolism.
- Hydrated carbonyl groups in AI-2 are crucial for binding to LsrR via hydrogen bonds.
Purpose of the Study:
- To explore geminal dihalogens as isosteric replacements for hydrated carbonyls.
- To investigate the potential of halogen bonding in ligand design.
- To assess the under-utilization of geminal dihalogens in medicinal chemistry.
Main Methods:
- Structural analysis of AI-2 binding to LsrR.
- Computational modeling of ligand-protein interactions.
- Synthesis and evaluation of geminal dihalogen compounds as AI-2 mimics.
Main Results:
- Hydrated carbonyls in AI-2 form key hydrogen bonds with LsrR.
- Geminal dibromides can effectively recapitulate these interactions through halogen bonding.
- Geminal dihalogens show promise as bioisosteres for hydrated carbonyls.
Conclusions:
- Geminal dihalogens are viable isosteric replacements for hydrated carbonyl groups.
- Halogen bonding offers a powerful, under-utilized tool for ligand design.
- This research opens new avenues for developing novel therapeutic agents targeting bacterial QS systems.
More Related Videos
Related Concept Videos
02:45Alkyl Halides
22.9K
Structural Properties
Alkyl halides are halogen-substituted alkanes wherein one or more hydrogen atoms of an alkane is replaced by a halogen atom such as fluorine, chlorine, bromine, or iodine. The carbon atom in an alkyl halide is bonded to the halogen atom, which is sp3-hybridized and exhibits a tetrahedral shape.
Unlike alkyl halides, compounds in which a halogen atom is bonded to an sp2 -hybridized carbon atom of a carbon-carbon double bond (C=C) are called vinyl halides. Whereas aryl...
Alkyl halides are halogen-substituted alkanes wherein one or more hydrogen atoms of an alkane is replaced by a halogen atom such as fluorine, chlorine, bromine, or iodine. The carbon atom in an alkyl halide is bonded to the halogen atom, which is sp3-hybridized and exhibits a tetrahedral shape.
Unlike alkyl halides, compounds in which a halogen atom is bonded to an sp2 -hybridized carbon atom of a carbon-carbon double bond (C=C) are called vinyl halides. Whereas aryl...
22.9K
01:24ortho–para-Directing Deactivators: Halogens
7.2K
Halogens are ortho–para directors. They are more electronegative than carbon. Therefore, as ring substituents, they can withdraw electrons through the inductive effect and deactivate the aromatic ring towards electrophilic substitution. Halogens also have an electron-donating resonance effect on the ring, which influences the orientation of the incoming electrophile. If an electrophile attacks at the ortho or the para position, the halogen donates electrons and stabilizes the intermediate...
7.2K
01:19Diazonium Group Substitution: –OH and –H
3.5K
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
3.5K
02:38Electrophilic Addition to Alkynes: Halogenation
10.7K
Introduction
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
10.7K
02:35Electrophilic Addition to Alkynes: Hydrohalogenation
12.3K
Electrophilic addition of hydrogen halides, HX (X = Cl, Br or I) to alkenes forms alkyl halides as per Markovnikov's rule, where the hydrogen gets added to the less substituted carbon of the double bond. Hydrohalogenation of alkynes takes place in a similar manner, with the first addition of HX forming a vinyl halide and the second giving a geminal dihalide.
12.3K
02:46Halogenation of Alkenes
21.6K
Halogenation is the addition of chlorine or bromine across the double bond in an alkene to yield a vicinal dihalide. The reaction occurs in the presence of inert and non-nucleophilic solvents, such as methylene chloride, chloroform, or carbon tetrachloride.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
21.6K