Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Basicity of Aromatic Amines

Basicity of Aromatic Amines

The basicity of aromatic amines is much weaker than that of aliphatic amines due to the involvement of the lone pair of electrons over the N atom in resonance with the aryl rings. Generally, the electron-donating ability of any substituents on the aryl ring of aromatic amines increases the basicity of the amine by increasing electron density, and hence the availability of lone pair on the nitrogen. On the other hand, electron-withdrawing functional groups on the aryl ring of amines decrease the...

Frost Circles for Different Conjugated Systems

Frost Circles for Different Conjugated Systems

The inscribed polygon method is consistent with Hückel’s 4n + 2 rule and helps to learn whether the given cyclic compound is aromatic or not. The compound is stable and aromatic if every bonding molecular orbital (MO) is completely filled with a pair of electrons. However, if the non-bonding or antibonding orbitals are filled with electrons, the compound is unstable and not aromatic. Consider the Frost circle diagrams for cycloalkenes containing 4 to 8 carbons.

VSEPR Theory and the Effect of Lone Pairs

VSEPR Theory and the Effect of Lone Pairs

Effect of Lone Pairs of Electrons on Molecule Geometry

Basicity of Heterocyclic Aromatic Amines

Basicity of Heterocyclic Aromatic Amines

Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).

¹H NMR: Long-Range Coupling

¹H NMR: Long-Range Coupling

The coupling interactions of nuclei across four or more bonds are usually weak, with J values less than 1 Hz. While these are usually not observed in spectra, the presence of multiple bonds along the coupling pathway can result in observable long-range coupling.
In alkenes, spin information is communicated via σ–π overlap, as seen in allylic (four-bond) and homoallylic (five-bond) couplings. These coupling interactions are stronger when the σ bond is parallel to the alkene π orbitals.

Criteria for Aromaticity and the Hückel 4n + 2 Rule

Criteria for Aromaticity and the Hückel 4n + 2 Rule

Like benzene, cyclobutadiene and cyclooctatetraene are cyclic compounds with alternate single and double bonds. However, their chemical behavior differs from benzene, as they are unstable and not aromatic. So, what are the structural characteristics of unsaturated compounds categorized as aromatic?
For the first time, Eric Hückel, a German chemical physicist, derived a set of structural features for a compound to be classified as aromatic. This is now known as Hückel’s rule or the 4n + 2 rule.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

A Postsynthetic Strategy for Oligonucleotides Containing 2-Fluoro-adenine and Isoguanine Nucleobases.

Organic letters·2026

Same author

Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.

Nucleic acids research·2026

Same author

A metal ion-dependent mechanism promoting gain of function in NEIL1 variants.

International journal of radiation biology·2026

Same author

Synthesis of siRNAs containing carbocyclic nucleotides and the role of cyclopentane conformation in RNAi activity.

RSC chemical biology·2026

Same author

New targets and procedures for validating the valence geometry of nucleic acid structures.

Nucleic acids research·2026

Same author

Protocols to evaluate mutant specificity of an oncogene-targeting siRNA using orthogonal in vitro and in vivo approaches.

STAR protocols·2026

Search research articles

Related Experiment Video

Updated: Jul 16, 2026

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Published on: April 19, 2019

Lone pair-aromatic interactions: to stabilize or not to stabilize.

Martin Egli¹, Sanjay Sarkhel

¹Department of Biochemistry, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232, USA. martin.egli@vanderbilt.edu

Accounts of Chemical Research

|March 21, 2007

Summary

Lone pair-pi (lp...pi) interactions involving aromatic rings are more common in nucleic acids than previously thought. Significant binding energies occur when the aromatic system is positively polarized, such as in protonated nucleobases.

Related Experiment Videos

Last Updated: Jul 16, 2026

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Published on: April 19, 2019

Area of Science:

Biochemistry
Structural Biology
Computational Chemistry

Background:

Aromatic rings are known hydrogen bond acceptors (D-H...pi interactions) in protein structures.
Other noncovalent interactions, specifically lone pair...pi (lp...pi) interactions, are less understood in macromolecules.
Recent interest in lp...pi interactions has focused on small-molecule models.

Purpose of the Study:

To investigate the occurrence and energetics of lp...pi interactions in crystal structures of DNA, RNA, and proteins.
To compare lp...pi interactions with well-established D-H...pi interactions in biological macromolecules.
To determine the factors influencing the binding energy of lp...pi interactions.

Main Methods:

Crystal structure analysis of DNA, RNA, and protein datasets.
Identification and quantification of lp...pi interaction geometries.
Ab initio quantum mechanical calculations to estimate interaction energies.

Main Results:

Lone pair...pi interactions were found to be more prevalent in nucleic acid structures compared to proteins.
Significant binding energies for lp...pi interactions were observed primarily when the aromatic system was positively polarized.
Protonation of nucleobases was identified as a key factor leading to positively polarized aromatic systems.

Conclusions:

Lone pair...pi interactions are an underappreciated noncovalent interaction in biological systems, particularly in nucleic acids.
The energetic contribution of lp...pi interactions is highly dependent on the electronic properties of the aromatic system.
Positively polarized aromatic systems, such as protonated nucleobases, can significantly stabilize nucleic acid structures through lp...pi interactions.