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Listening to "molecular song" via IR spectroscopy and scanning tunneling microscopy

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Listening to "molecular song" via IR spectroscopy and scanning tunneling microscopy

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Listening To A Single Molecule Sing Its Own Name

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At 7 kelvin — a temperature so cold that even air would freeze solid — a single molecule sits on a copper surface. It is, by most reckoning, one of the

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2D NMR techniques, such as COSY and HSQC, take this technology to a new level by revealing complex connections between atoms

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2D NMR techniques, such as COSY and HSQC, take this technology to a new level by revealing complex connections between atoms

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Microbiology and Cell Biology, Medicinal Chemistry - Emery Pharma

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Nuclear Magnetic Resonance (NMR) spectroscopy is an incredibly powerful tool for characterizing molecular structures. When submitting to the FDA or other regulatory agencies, full structural characterization by NMR provides crucial evidence of compound identity. A combination of 1-dimensional and 2-dimensional NMR experiments are necessary for complete confidence in chemical structure. This post will walk you through the steps to fully characterize a molecule by 1- and 2-dimensional NMR, including on how to perform NMR interpretation.

Step 1: ¹H-NMR

The first step in structural characterization is 1-dimensional proton ¹H-NMR. The chemical shift, multiplicity, coupling constants, and integration are all factors to consider when assigning protons. In this example, only three protons can be assigned by the proton spectrum alone: protons 3, 4, and 6.

Chemical Shift (ppm)

Multiplicity

Coupling Constant (Hz)

Integration

To begin, let's start with proton 3. Proton 3 is the only methyl group in the structure, and therefore must integrate to 3 protons. The only peak with an integration of 3 is the doublet at 1.770 ppm. The high field chemical shift supports this assignment. The peak is split into a doublet with a coupling constant of 1.2 Hz, reflecting the long-range coupling between protons 3 and 4, which also supports this assignment.

Protons that are coupled to each other should exhibit the same coupling constant. The long-range coupling constant observed for proton 3 (J=1.2 Hz, split into a doublet by proton 4) is reflected in the coupling constant for proton 4 (J=1.2 Hz, split into a quartet by proton 3). Therefore, the peak at 7.690 ppm must represent proton 4! The integration and chemical shift support the assignment, as proton 4 is the only aromatic proton in the structure.

There is only one singlet in the ¹H-NMR spectrum. The only proton that should show up as a singlet is proton 6, as it has no neighboring protons that would split the peak (the nearest proton is 5 bonds away!). The chemical shift of 11.256 ppm supports this assignment, as imide protons often show up far downfield. The peak also integrates to 1 proton, supporting the assignment.

The remaining protons are doublets, triplets, and multiplets that can be assigned by 2-dimensional COSY.

Step 2: ¹H-¹H COSY

¹H-¹H Correlation Spectroscopy (COSY) shows the correlation between hydrogens which are coupled to each other in the ¹H NMR spectrum. The ¹H spectrum is plotted on both 2D axes. While 2-bond and 3-bond ¹H-¹H coupling is easily visible by COSY, long range coupling can also be observed with long acquisition times. The cross-peaks (not on the diagonal) that are symmetric to the diagonal show the COSY correlations. For example, protons 3 and 4 are coupled to each other, since they form a box pattern symmetric to the diagonal. This confirms assignments 3 and 4 made from the proton spectrum alone.

Two types of COSY coupling: 3-bond short range coupling between protons 7 and 8 (red) and 4-bond long range coupling between protons 3 and 4 (blue).

My favorite way to analyze a COSY spectrum with many unassigned protons is to make a table of correlations, like the one seen here. Look at the table for any clear differences in correlation and begin there! In this example, all unassigned protons show one or two COSY correlations-except the proton at 4.233 ppm, which correlates to three other protons by COSY. The only proton expected to correlate with three nonequivalent protons is proton 9!

Chemical Shift
(ppm)

COSY
correlations

Assignment

Now that proton 9 has been assigned, the fun really begins. Thymidine's structure suggests that proton 9 should couple protons 8, 10, and 11. Based on the COSY, proton 9 couples protons at 2.068 ppm (2H), 3.754 ppm (1H), and 5.209 ppm (1H). From this list, we can easily assign proton 8 as the peak at 2.068 ppm based on its integration of 2 protons. To differentiate protons 10 and 11, take a look at our COSY table; 3.754 ppm shows two COSY correlations, while 5.209 ppm only shows one. Therefore, we can assign proton 10 as 5.209 ppm and proton 11 as 3.754 ppm.

Once proton 8 has been assigned, we can easily assign proton 7 based on the remaining COSY correlation for proton 8. Proton 7's peak at 6.163 ppm is split into a triplet by the two 8 protons, confirming the assignment.

All that remains are protons 12 and 13. We can assign proton 12 (3.564 ppm) based on its integration of 2H and its COSY correlation to proton 11. The last remaining peak at 4.999 ppm must be proton 13; this is confirmed by COSY correlation with proton 12, triplet multiplicity based on splitting by proton 12, and integration of one proton.

Now we have a fully assigned ¹H-NMR spectrum! This spectrum will help us assign our carbons using HSQC and HMBC NMR spectroscopy.

Step 3: ¹³C-NMR

Carbon NMR is a necessary step in full structural characterization. However, ¹³C-NMR alone does not provide enough information to assign the carbons in the molecule. The NMR spectrum below does confirm the number of carbons in the molecule; however, HSQC and HMBC (we will get to these soon!) are necessary to assign the carbons with confidence. Note that one of the carbons is hidden beneath the solvent signal but is clearly visible after zooming into that region.

Step 4: DEPT-45, 90, and 135

Distortionless Enhancement of Polarization Transfer (DEPT) experiments help assign carbon peaks by determining the number of protons attached to each carbon. For very simple molecules, DEPT may be enough to partially or fully assign all carbons. In complex molecules, DEPT and HSQC together are useful for confirming both carbon and proton assignments. For example, the DEPT experiments below can only identify carbon 3-it is the only CH₃ peak. I always go back and use DEPT to confirm the carbons I assigned by HSQC.

DEPT-45 shows CH, CH₂, and CH₃ carbons as positive peaks. Carbons with no protons are not visible.

DEPT-90 shows only CH peaks as positive peaks. Carbons with no protons, CH₂, and CH₃ carbons are not visible.

DEPT-135 shows CH and CH₃ carbons as positive peaks and CH₂ carbons as negative peaks. Carbons with no protons are not visible.

Step 5: ¹H-¹³C HSQC

¹H-¹³C Heteronuclear Single Quantum Coherence Spectroscopy (HSQC) shows which hydrogens are directly attached to which carbon atoms. The ¹H spectrum is shown on the horizontal axis and the ¹³C spectrum is shown on the vertical axis. The HSQC spectrum is most valuable when protons have already been assigned.

For example, HSQC shows a correlation between proton 4 and the carbon at 136.113 ppm; this carbon is now assigned as carbon 4. Carbons 3, 4, 7, 8, 9, 11, and 12 are assigned by HSQC. Only 1-bond correlations are observed, so HSQC assignments are relatively straightforward. The DEPT experiments also confirm these assignments. HSQC is also useful in confirming proton assignments of nitrogen or oxygen-bound protons; they show no signal by HSQC. This further supports the assignments of protons 6, 10, and 13.

An example correlation between proton and carbon 4 is observed by HSQC.

Step 6: ¹H-¹³C HMBC

¹H-¹³C Heteronuclear Multiple Bond Correlation Spectroscopy (HMBC) shows the correlations between protons and carbons that are separated by multiple bonds. The ¹H spectrum is shown on the horizontal axis and the ¹³C spectrum is shown on the vertical axis. Correlated atoms are shown in blue and the connecting atoms are shown in red. Note that direct hydrogen-carbon bonds (1-bond correlations) are generally not seen. For example, hydrogen 4 shows correlations with carbons 1, 2, 3, 5, and 7, but not carbon 4.

HMBC interactions between proton 4 and carbons 1, 2, 3, 5, and 7.

HMBC is incredibly useful for assigning carbons that have no protons attached. In this example, carbons 1, 2, and 5 have no protons attached. Carbon 1 is assigned by HMBC interactions with protons 3, 4, and 6; carbon 2 by interaction with protons 3, 4, 6, and 7; and carbon 5 by interactions with protons 4 and 7 only. The chemical environment of carbon 5 suggests it would appear more downfield than carbon 1, which confirms these assignments.

HMBC also confirms assignments that were based solely on the proton and COSY spectrum. For example, protons 10 and 13 are differentiated by HMBC; proton 10 is confirmed by interactions with carbons 8, 9, and 11 , while proton 13 is confirmed by interactions with 11 and 12. HMBC supports all proton and all carbon assignments, unambiguously confirming both the structure and analysis of thymidine.

At Emery Pharma, we are experts in 1D and 2D NMR characterization and structure elucidation; in fact, 2D NMR projects are some of our favorites! We have supported numerous pharmaceutical companies in full NMR characterization for API submissions to regulatory agencies, as well as complete structure elucidation of impurities. We provide a fully annotated report with images similar to those seen here and support our results with high resolution mass spectrometry and elemental analysis. For more information on our NMR services, including GLP/cGMP or R&D projects, please visit our NMR Services page, or contact us at [email protected] .

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A Step-By-Step Guide to 1D and 2D NMR Interpretation

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Nuclear Magnetic Resonance (NMR) spectroscopy is an incredibly powerful tool for characterizing molecular structures. When submitting to the FDA or other regulatory agencies, full structural characterization by NMR provides crucial evidence of compound identity. A combination of 1-dimensional and 2-dimensional NMR experiments are necessary for complete confidence in chemical structure.

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For those interested, here's a well-organized introduction to carbon-13 NMR

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For those interested, here's a well-organized introduction to carbon-13 NMR

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Last updated: March 21st, 2025 |
Chemical Shift Equivalence - How Many Unique Signals? ¹³ C NMR (proton-decoupled)
Just like with H NMR, chemical shift equivalence applies to C NMR. A spectrum produced by a C NMR experiment may not always display a 1:1 ratio of signals to individual carbons atoms. When two or more carbon atoms in a molecule have chemically equivalent nuclei, instead of producing two or more signals on a C NMR spectrum, they will produce one signal at a specific chemical shift that will represent those equivalent carbons. In order for atoms to be chemically equivalent, their nuclei must be interchangeable through the performance of symmetry operations (planes of symmetry) or rapid intramolecular processes (bond rotation or tautomerization). Carbon atoms with chemical equivalence may be homotopic (identical) or enantiotopic (equivalent in achiral solvents).
Table of Contents

1. Methane: One Carbon, One Signal

2. Ethane Has Two Carbons, But Only One Signal Due To Symmetry

3. Pentane (5 Carbons) Has Only Three 13C NMR Signals Due To Symmetry

4. Symmetry In Aromatic Rings

5. Some Quick Examples

6. Slight Disruptions To Symmetry Can Have A Large Impact On The Number Of Signals In A ¹³C NMR Spectrum

7. Ortho, Meta, and Para Di-Substituted Aromatic Rings: Look Out For Planes Of Symmetry!

8. The Effect Of Chirality Centers On 13C NMR Spectra

9. Carbons That Are Equivalent Through Fast Bond Rotation Will Have Their Signals Averaged Together

10. Some More Practice Examples

11. Quiz Yourself!

1. Methane: One Carbon, One Signal

2. Ethane Has Two Carbons, But Only One Signal Due To Symmetry

While ethane does contain two carbon atoms, two signals will NOT be produced. We can see by looking at the molecule that ethane contains a mirror plane of symmetry, bisecting it in half. If we perform a symmetry operation by flipping ethane 180º at a time (along its C mirror plane axis), we can see that the molecule's carbon atoms are identical in their environments, making them interchangeable. This results in the chemical equivalence of the two carbon atoms of ethane, producing a single signal in a C NMR spectrum.

3. Pentane (5 Carbons) Has Only Three ¹³C NMR Signals Due To Symmetry

4. Symmetry In Aromatic Rings

Toluene contains a mirror plane. If we identify that mirrorplane and perform rotational operations about it, we can see that two pairs of equivalent carbon atoms are present in addition to three non-equivalent ones. This adds up to a total of 5 different carbon atoms that will produce signals at 5 separate chemical shifts on a spectrum. Despite the molecule containing seven carbon atoms total, only 5 signals will be produced.

5. Some Quick Examples

Each of these compounds produce 3 signals! Like the previous examples, we can confirm carbon atom equivalence through observing a molecule's planes of symmetry.

6. Slight Disruptions To Symmetry Can Have A Large Impact On The Number Of Signals In A ¹³C NMR Spectrum

These two ethers that contain the same number carbon atoms will yield a different number of signals on a C NMR spectrum. Dibutyl ether contains eight carbons but will produce a total of 4 signals due to its bisecting mirror plane that results in each carbon atom being part of a homotopic pair. Pentyl propyl ether also contains eight carbons, but the mirror plane present (running through the chain of atoms) does not bisect the molecule to make any of the carbon atoms equivalent. This results in pentyl propyl ether producing a total of 8 signals in a C NMR spectrum that represent each of its 8 individual carbon atoms.

7. Ortho, Meta, and Para Di-Substituted Aromatic Rings: Look Out For Planes Of Symmetry!

How about some regioisomer examples to practice?

While regioisomers contain the same number of carbon atoms, they differ in that their substituents are positioned in different chemical environments. These structural differences result in differing symmetries among the molecules, which correspond to each molecule having different pairs of homotopic carbons. A difference in chemical environments will cause a difference in chemical shifts, while a difference in quantities of equivalent and non-equivalent carbons cause a change in the number of signals.

8. The Effect Of Chirality Centers On 13C NMR Spectra

Let's take a look at a chiral molecule. How many signals would you expect to be produced from the compound below?

9. Carbons That Are Equivalent Through Fast Bond Rotation Will Have Their Signals Averaged Together

As we can see in the example above, the stereochemistry of a compound can affect the number of signals produced on a spectrum. What about conformers? Would different conformations of a molecule always affect the number of signals? Lets take a look at 2,2,3,3-tetramethylbutane.

Just as we observe in H MNR, the same chemical equivalence through rapid bond rotation occurs in C NMR. While the rotations of H NMR, t-butyl groups occur about the central C-C bond of the compound, they are fast enough relative to the NMR "shutter speed" that the carbon atoms become equivalent, blurring together like the spinning of a bicycle wheel or blades of a fan. The resulting signal produced on the spectrum that corresponds to these atoms will represent the average of the carbon atoms in the different conformers. So in this case, conformers can be ignored and a total of two signals will be visible on a spectrum. It is important to remember that unlike C NMR peak ratios are not to be used quantitatively. This spectrum only supplies the qualitative information that there are two types of carbon atoms present in the molecule. It does not specify any quantities of its primary and tertiary carbons.

10. Some More Practice Examples

Let's apply the information we've learned so far to some practice problems.

11. Summary

Just as in H NMR, a molecule's symmetry will greatly affect the number of signals it produces on a C NMR spectrum. Finding any mirror planes present and performing the necessary symmetry operations greatly simplifies predicting the outcomes of this spectroscopic method.

This article was contributed by Nick Tiedemann. Thanks Nick!

Notes

Quiz Yourself!

Become a MOC member to see the clickable quiz with answers on the back.

Become a MOC member to see the clickable quiz with answers on the back.

Become a MOC member to see the clickable quiz with answers on the back.

Become a MOC member to see the clickable quiz with answers on the back.

Become a MOC member to see the clickable quiz with answers on the back.

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13-C NMR - How Many Signals - Master Organic Chemistry

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Chemical Shift Equivalence - How Many Unique Signals? 13C NMR (proton-decoupled) Just like with 1H NMR, chemical shift equivalence applies to 13C NMR. A spectrum

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Automated chemical profiling of wine by solution NMR spectroscopy

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Automated chemical profiling of wine by solution NMR spectroscopy

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fact-checked

peer-reviewed publication

trusted source

proofread

Credit: Journal of Chemical Education (2026). DOI: 10.1021/acs.jchemed.5c00652

New work from Georgia Tech is showing how a simple glass of wine can serve as a powerful gateway for understanding advanced research and technologies. The project, inspired by an Atlanta Science Festival event hosted by School of Chemistry and Biochemistry Assistant Professor Andrew McShan, develops an innovative outreach and teaching module around nuclear magnetic resonance (NMR) techniques, and is designed for easy adoption in introductory chemistry and biochemistry courses.

Published earlier this year in the Journal of Chemical Education, the study, "Automated Chemical Profiling of Wine by Solution NMR Spectroscopy: A Demonstration for Outreach and Education" was led by a team from the School of Chemistry and Biochemistry including lead author McShan, Ph.D. students Lily Capeci, Elizabeth A. Corbin, Ruoqing Jia, Miriam K. Simma, and F. N. U. Vidya, Academic Professional Mary E. Peek, and Georgia Tech NMR Center Co-Directors Johannes E. Leisen and Hongwei Wu.

"NMR is one of the most widely used analytical tools in chemistry and the life sciences, and Georgia Tech hosts one of the most cutting-edge NMR centers in the world," McShan says. "Our study shows that you don't need advanced training to appreciate how powerful tools like NMR work and how those tools are used in research."

All materials, tutorials, and data are freely available via online tutorials and a YouTube video, enabling educators to replicate or adapt the activity even in settings with limited access to NMR facilities.

Wine sleuthing at the Atlanta Science Festival

From families with K-12 students to undergraduates to adults with no prior chemistry experience, nearly 130 visitors explored wine chemistry at the Georgia Tech NMR Center during the Atlanta Science Festival event. With McShan's guidance, they identified and quantified more than 70 chemical components that influence wine taste, aroma, and quality by analyzing the chemical composition, structure, and dynamics of molecules.

Taking on the role of wine investigators (a real-world application of NMR), the group investigated examples of wine fraud, learning to identify harmful additives like methanol, antifreeze, and lead acetate-additives that played roles in both historical and modern wine scandals.

"By connecting the science to something familiar like wine, we were able to spark curiosity and excitement across age groups," says McShan. "This a framework for how complex analytical techniques can be made inclusive, interactive, and inspiring whether in the classroom or at a science festival."

Science for all

The study underscores the potential of NMR and other powerful technologies as outreach opportunities-from engaging the public to better teaching undergraduate students.

"After the event, adults said they learned how chemical composition affects wine characteristics and how NMR is used in research and industry," McShan says. "Younger participants learned key concepts about wine composition and found benefits from the sensory elements, like watching the spectrometer in action."

They aim to use these takeaways to continue developing outreach tools. "My end goal is to develop NMR into a practical teaching tool by grounding the technique in real-world examples," adds McShan. "Using this approach is a clear avenue to introducing the general public to the world-class instruments used by researchers at Georgia Tech and exposing undergraduate students to the powerful analytical techniques they are likely to encounter throughout their careers."

Publication details

Lily Capeci et al, Automated Chemical Profiling of Wine by Solution NMR Spectroscopy: A Demonstration for Outreach and Education, Journal of Chemical Education (2026). DOI: 10.1021/acs.jchemed.5c00652

Citation: What's in your wine? Using NMR to reveal its chemical profile (2026, February 14) retrieved 6 May 2026 from https://phys.org/news/2026-02-wine-nmr-reveal-chemical-profile.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

# data[].attributes.attachment_link.title
What's in your wine? Using NMR to reveal its chemical profile

# data[].attributes.attachment_link.description
New work from Georgia Tech is showing how a simple glass of wine can serve as a powerful gateway for understanding advanced research and technologies. The project, inspired by an Atlanta Science Festival event hosted by School of Chemistry and Biochemistry Assistant Professor Andrew McShan, develops an innovative outreach and teaching module around nuclear magnetic resonance (NMR) techniques, and is designed for easy adoption in introductory chemistry and biochemistry courses.

# data[].attributes.headline
Novel tools for automated structure determination via IR and NMR

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Novel tools for automated structure determination via IR and NMR

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Infrared and NMR fusion boosts automated structure verification

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Study highlights untapped potential of IR spectroscopy data

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Learn about various applications of spectroscopy in astronomy!

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Learn about various applications of spectroscopy in astronomy!

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Spectroscopy 101 – Types of Spectra and Spectroscopy - NASA Science

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The basic premise of spectroscopy is that different materials emit and interact with different wavelengths (colors) of light in different

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Researchers have developed a novel reaction that converts chiral molecules into the opposite stereoisomer

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Researchers have developed a novel reaction that converts chiral molecules into the opposite stereoisomer

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Chirality-flipping reaction could completely change total synthesis strategies

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Photocatalytic reaction that inverts configuration of chiral carbon centres offers new stereochemical editing logic

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The toolbox of organic reactions capable of adding, deleting and switching single atoms in rings is ever-expanding

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The toolbox of organic reactions capable of adding, deleting and switching single atoms in rings is ever-expanding

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Nina Notman meets the chemists expanding the toolbox of reactions capable of adding, deleting and switching single atoms in rings at the heart of organic molecules

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Total synthesis of alkaloid with potential applications in the treatment of drug addiction and depression in just seven steps (!)

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Total synthesis of anti-addictive alkaloid in just seven steps

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A streamlined synthesis of the psychoactive compound ibogaine could open up new opportunities in the treatment of drug addiction and depression

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Scientists have created a new rhenium-based catalyst that can carefully rearrange alkynes in a controlled way, helping synthetic chemists.

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Scientists have created a new rhenium-based catalyst that can carefully rearrange alkynes in a controlled way, helping synthetic chemists.

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Air-stable rhenium complex catalyses alkyne metathesis

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Study presents first non-d0 alkylidyne complex capable of effecting alkyne metathesis at room temperature

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Using quantum chemistry to better understand the Diels-Alder reaction.

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Using quantum chemistry to better understand the Diels-Alder reaction.

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Credit: Catalysis Science & Technology (2025). DOI: 10.1039/D4CY01192A

Chemical research is often a process of trial and error. Things often don't go as expected in the laboratory: reactions stall or produce too little product. Knowledge of the chemical properties of the substances involved is then no longer sufficient. Instead, chemists would like to look deeper into the reaction, down to the subatomic level.

This is possible with high-tech analytics. And quantum chemistry is also increasingly in demand, as it can reveal critical moments in the catalytic process solely through calculation, e.g., of the behavior of electrons. Dr. Olga Bokareva heads this work at LIKAT in Rostock. A current example is a novel Diels-Alder reaction.

Increasing computing power and ever-improving algorithms have made the modeling of chemical reactions indispensable in research. "This is particularly true where chemistry is breaking new ground, for example in replacing fossil raw materials with by-products of civilization. Or in expanding the range of applications for classic and proven processes and using them for sustainable processes," says Dr. Bokareva, head of a junior research group at the Leibniz Institute for Catalysis.

Diels-Alder reloaded: More effective with electricity

The chemist cites the Diels-Alder reaction as a current example. For three quarters of a century, it has had a firm place in organic chemistry, especially in the synthesis of active pharmaceutical ingredients and other complex molecules. Its discoverers were awarded the Nobel Prize in 1950.

Several laboratories are currently attempting to make the Diels-Alder reaction usable for far more complex syntheses than has been possible to date. At LIKAT, this has been achieved by electrochemical means. Dr. Bokareva explains, "Electrodes in the reaction solution provide a current that drives the process and makes it much more effective than the classic Diels-Alder reaction."

Scientific Director of LIKAT, Prof. Dr. Robert Franke, collaborated with colleagues from Japan on this project, and together they submitted a paper. Their experiments had shown that the electrochemical Diels-Alder reaction works wonderfully with certain starting materials, but not at all with others. The authors offered some hypotheses as to the causes. However, the journal requested a detailed mechanistic explanation using quantum chemical methods.

This is where the expertise of Dr. Bokareva and her team came into play. A doctoral student, Yanan Han, took on the work as part of her dissertation.

Comparable to Google Maps

To understand the reaction mechanism, the team used quantum chemistry to calculate the energy of the molecules along the reaction pathway. All they needed to know was the starting material and the product, as well as some information about the reaction conditions, such as the temperature. Dr. Bokareva compares this approach to Google Maps: "You know your location and destination and want to avoid traffic jams; in the reaction, this could be an undesirable intermediate product. The program calculates the best route."

Such quantum chemical calculations do not provide exact values, but rather approximations, Dr. Bokareva explains. The current state of individual molecules is determined by the difference between their energy states. The reason for this lies in the quantum nature of electrons, which are described by wave functions.

The mathematical foundations for such calculations were developed about a hundred years ago, such as the Schrödinger equations, which Dr. Bokareva and her team use together with numerical methods.

Electron clouds determine the reaction

Today, the results can be represented graphically, for example as orbitals, which is the name given to the locations of electrons in atoms. On the screen, they appear as colored structures reminiscent of floating balloons. "We often talk about electron clouds when we mean the diffuse space where electrons are located," says Dr. Bokareva. Such representations help not only to analyze reaction processes, but also to understand them intuitively. "Quantum chemistry is not only challenging, it is also beautiful."

Discover the latest in science, tech, and space with over 100,000 subscribers who rely on Phys.org for daily insights. Sign up for our free newsletter and get updates on breakthroughs, innovations, and research that matter- daily or weekly.

What did the calculations for the novel Diels-Alder reaction show? "We were able to identify an intermediate product that is formed at a critical moment in the process," says Dr. Bokareva. For the reaction to continue, this intermediate product needs an additional electron. The system must allow this electron transfer to occur energetically, and the researchers were able to identify specific conditions for this in the behavior of the electron clouds. These conditions were not met in the problematic substrates, and the reaction broke down.

The reason for the disruption has therefore been found, and the findings have now been published jointly with partners from Japan in Catalysis Science & Technology. According to Dr. Bokareva, the work offers approaches for making substrates that have not been successful to date usable for electrochemical Diels-Alder synthesis. For example, by changing the electronic structure of these compounds or the electrochemical reaction conditions.

More information

Haruka Morizumi et al, Controlling the reactivity of enol ether radical cations via the substitution pattern: investigation into electrochemically induced Diels-Alder reactions, Catalysis Science & Technology (2025). DOI: 10.1039/D4CY01192A

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Quantum chemistry reveals how electron behavior shapes electrochemical Diels-Alder reactions

# data[].attributes.attachment_link.description
Chemical research is often a process of trial and error. Things often don't go as expected in the laboratory: reactions stall or produce too little product. Knowledge of the chemical properties of the substances involved is then no longer sufficient. Instead, chemists would like to look deeper into the reaction, down to the subatomic level.

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Researchers used a palladium-based cage to induce a tetradehydro-Diels–Alder reaction to form polycyclic systems.

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Researchers used a palladium-based cage to induce a tetradehydro-Diels–Alder reaction to form polycyclic systems.

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Molecular cage seizes control in tetradehydro Diels–Alder reaction

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Elegant method dodges harsh reaction conditions to assemble polycyclic scaffolds from simple linear precursors

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An unusual ‘quasi-benzyne’ radical anion generated from water microdroplets could represent a new substrate class in catalyst-free Diels–Alder reactions. 

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An unusual ‘quasi-benzyne’ radical anion generated from water microdroplets could represent a new substrate class in catalyst-free Diels–Alder reactions. 

# data[].attributes.attachment_link.title
Water microdroplet chemistry enables catalyst-free Diels–Alder reaction

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‘Quasi-benzyne’ radical drives exotic reactivity

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Why are all proteins ‘left-handed’? New theory could solve origin of life mystery.

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Nitrogen chiral centers are rare, but it looks like they're possible. This article provides a good review.

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Nitrogen chiral centers are rare, but it looks like they're possible. This article provides a good review.

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Stable nitrogen chiral centres are possible – under the right conditions

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Chiral nitrogen compounds might one day be used as reagents, catalysts or even as drugs

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Is it possible to create "mirror bacteria" - bacteria comprised entirely of molecules with the opposite stereochemical configuration? An interesting theoretical question!

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Is it possible to create "mirror bacteria" - bacteria comprised entirely of molecules with the opposite stereochemical configuration? An interesting theoretical question!

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Mirror Bacteria: Reflecting on Alternate Chirality | ASM.org

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X-ray diffraction is commonly used to determine the stereochemical configuration of molecules. Here's more information about how single-crystal x-ray diffraction is used in drug development.

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X-ray diffraction is commonly used to determine the stereochemical configuration of molecules. Here's more information about how single-crystal x-ray diffraction is used in drug development.

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Single-crystal x-ray diffraction (SCXRD) in drug development is evolving. Johnson Matthey outlines how technology advances and regulations are reshaping its role in pharma

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MIT chemists have synthesized a fungal compound which has shown potential as an anticancer agent. The compound, verticillin A, has 10 rings and eight stereocenters!

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MIT chemists have synthesized a fungal compound which has shown potential as an anticancer agent. The compound, verticillin A, has 10 rings and eight stereocenters!

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MIT News | Massachusetts Institute of Technology

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MIT chemists synthesize a fungal compound that holds promise for treating brain cancer

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MIT chemists synthesized a fungal compound that holds promise for treating brain cancer. Early studies find derivatives of the compound, verticillin A, can kill certain glioma cells.

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Multi-step synthesis is my favorite unit in organic chemistry. Learn about its evolution and future!

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Multi-step synthesis is my favorite unit in organic chemistry. Learn about its evolution and future!

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From structure confirmation to methodology improvements, making complex natural products has driven innovation in organic synthesis for decades. Nina Notman looks at its current state, with threats from funding to academic pressures

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Cubane: a weird-looking molecule that has actually been quite useful in synthetic and medicinal chemistry!

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Cubane: a weird-looking molecule that has actually been quite useful in synthetic and medicinal chemistry!

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Medicinal chemists are increasingly exploring strained ring systems, George Barsted reports, believing they can serve as replacements for conventional building blocks in pharmaceuticals

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Is a one electron bond between carbon atoms possible? Apparently, but it's complicated.

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Is a one electron bond between carbon atoms possible? Apparently, but it's complicated.

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One-electron covalent bond between two carbons pushes limits of bonding

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Linus Pauling proposed exotic bonds but they have never been seen between two carbons until now

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Efficient hydrogenation of nitrobenzene using a gold-cluster catalyst might make for easier synthetic preparation of acetaminophen (paracetamol).

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Efficient hydrogenation of nitrobenzene using a gold-cluster catalyst might make for easier synthetic preparation of acetaminophen (paracetamol).

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A new gold standard in selective nitrobenzene hydrogenation

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Reaction proceeds through a previously unidentified mechanism

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Interesting new synthetic methods for preparing complex alkenes in the laboratory from carboxylic acid, alcohol, and alkane starting materials. 

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Interesting new synthetic methods for preparing complex alkenes in the laboratory from carboxylic acid, alcohol, and alkane starting materials. 

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New catalytic strategies boost alkene synthesis

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Photocatalyst makes complex alkenes from acids, alkanes or alcohols, while a ‘phase-pure’ iron catalyst reduces unwanted Fischer-Tropsch waste products

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Metal–organic frameworks contain large cavities in which molecules can flow in and out.

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The Nobel Prize in Chemistry this year was awarded to Kitagawa, Robson, and Yaghi. Learn about their work on metal-organic frameworks!

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The Nobel Prize in Chemistry this year was awarded to Kitagawa, Robson, and Yaghi. Learn about their work on metal-organic frameworks!

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Giant molecular rings mimic the puckered shapes of cyclobutane, cyclopentane, and cyclohexane! 

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Giant molecular rings mimic the puckered shapes of cyclobutane, cyclopentane, and cyclohexane! 

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Giant molecular rings that mimic the puckered shapes of cyclobutane, cyclopentane and cyclohexane could offer new insights into conformational dynamics

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"Cyclopropyl effect" causes substituents on cyclohexane to favor axial conformation.

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"Cyclopropyl effect" causes substituents on cyclohexane to favor axial conformation.

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Cyclopropyl effect causes substituents on cyclohexane to favour axial conformation

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‘Unusual stereocontrol element’ will help medicinal chemists increase three-dimensionality of drug candidates

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Conformational studies of steroids are useful in interpreting their reactivity. Conformational drawings of fused-ring systems get really interesting!

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Conformational studies of steroids are useful in interpreting their reactivity. Conformational drawings of fused-ring systems get really interesting!

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The important class of lipids called steroids are actually metabolic derivatives of terpenes, but they are customarily treated as a separate group. Steroids may be recognized by their tetracyclic …

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Do you know what "fugitive pigments" are in art? I didn't.

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Do you know what "fugitive pigments" are in art? I didn't.

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Fugitive Pigments: Why Do They Fade, and Does it Matter?

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This article examines fugitive pigments, the science of lightfastness, and asks whether we can trust the ratings given by paint manufacturers.

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Why do some sunscreens turn clothes red when washed with bleach? Hint: It has to do with resonance!

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Why do some sunscreens turn clothes red when washed with bleach? Hint: It has to do with resonance!

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Why some sunscreens turn clothes crimson when bleached

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Laundry mishap leads researchers to a surprising substitution reaction

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Organic chemists have created an analogue of morphine that doesn't appear to yield addictive behavior patterns or reduced breathing rate.

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Organic chemists have created an analogue of morphine that doesn't appear to yield addictive behavior patterns or reduced breathing rate.

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Morphine analogues kill pain with fewer negative side effects

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Redesign of the potent painkiller’s core prevents breathing suppression and reduces addiction-related behaviours in mice

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Aromaticity explains benzene's unique stability, and it directly relates to resonance. The world's largest aromatic molecule was recently discovered - 242 π electrons participate!

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Aromaticity explains benzene's unique stability, and it directly relates to resonance. The world's largest aromatic molecule was recently discovered - 242 π electrons participate!

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Porphyrin ring pushes the size limit for fully aromatic molecules

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Nanoring structure features 18 porphyrin units linked together by butadiyne units

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Looks like d atomic orbitals can also combine to form sigma (σ) and pi (π) molecular orbitals, but also a third type called delta (δ). More about that here.

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Looks like d atomic orbitals can also combine to form sigma (σ) and pi (π) molecular orbitals, but also a third type called delta (δ). More about that here.

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In transition metals and other heavier elements, the \(d\) orbitals may combine with other orbitals of compatible symmetry (and energy) to form molecular orbitals. Generally, there are three types of bonding and antibonding interactions that may occur with \(d\) orbitals: sigma (\(\sigma\)), pi (\(\pi\)), and delta (\(\delta\)) bonds.

Figure \(\PageIndex{1}\): The five \(3d\) orbitals are shown. The orientation of the axes is consistent and the \(z\) axis is horizontal for convenience in drawing bonding along the \(z\) axis (see examples below). (CC-BY-SA; Kathryn Haas)

Sigma (\(\sigma\)) bonding with \(d\) orbitals

\(\sigma\) bonds are symmetric with respect to the inter-nuclear axis (in a diatomic molecule, this is the \(z\) axis). An example of a \(\sigma\) bond formed by \(d\) orbitals is that of two \(d_{z^2}\) orbitals (see Figure \(\PageIndex{2}\)). If a bonded atom is in a position other than on the \(z\) axis (in an octahedral geometry, for example), \(\sigma\) bonds can also form. For example, two \(d_{x^2-y^2}\) orbitals on atoms bonded along the \(x\) or \(y\) axes could also form a \(\sigma\) bond.

\(d\) orbitals can also form \(\sigma\) bonds with other types of orbitals with the appropriate symmetry. Examples of orbitals with appropriate symmetry are the \(s\) orbital and certain \(p\) orbitals on another atom, as shown below in Figure \(\PageIndex{2}\).

Figure \(\PageIndex{2}\): Selected examples of \(\sigma\) bonds involving \(d\) orbitals along the \(z\) internuclear axis (shown as a bold horizontal line) between two atoms. (CC-BY-SA; Kathryn Haas)

Pi (\(\pi\)) bonding with \(d\) orbitals

\(\pi\) bonds are those with one node that is in-plane with the internuclear axis. A \(\pi\) bond can form between two \(d\) orbitals or between \(d\) orbitals and other types of orbitals with comparable symmetry. An example of a \(\pi\) bond between two \(d\) orbitals is that formed by two \(d_{xz}\) orbitals along the \(z\) axis (shown in Figure \(\PageIndex{3}\)). \(d\) orbitals can also form \(\pi\) bonds using \(p\) orbitals with compatible symmetry, as shown in Figure \(\PageIndex{3}\).

Figure \(\PageIndex{3}\): Selected examples of \(\pi\) bonds involving \(d\) orbitals along the \(z\) internuclear axis (shown as a bold horizontal line) between two atoms. (CC-BY-SA; Kathryn Haas)

Delta (\(\delta\)) bonding with \(d\) orbitals

\(\delta \) bonds are those with two nodes that are in-plane with the internuclear axis. \(\delta\) bonds can form between two \(d\) orbitals with appropriate symmetry. For example, when two atoms bond along the \(z\) axis, the \(d_{xy}\) orbitals and the two \(d_{x^2-y^2}\) orbitals can form \(\delta\) bonds (Figure \(\PageIndex{4}\)).

Figure \(\PageIndex{4}\): Selected examples of \(\delta\) bonds involving \(d\) orbitals along the \(z\) internuclear axis (shown in bold horizontal line) between two atoms. (CC-BY-SA; Kathryn Haas)

Incompatible orbitals

In the descriptions above, we focused on how bonds (and antibonds) can be formed with \(d\) orbitals. All bonding and non-bonding interactions require that orbitals have compatible symmetry to form productive interactions. It is worth mentioning that orbitals with symmetry that is incompatible with the \(d\) orbitals will not have bonding or antibonding interactions with \(d\) orbitals. The figure below shows several sets of orbitals that are incompatible for bonding.

Figure \(\PageIndex{5}\): Several incompatible pairs of orbitals. (CC-BY-SA; Kathryn Haas)

Curated or created by Kathryn Haas

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5.1.3: Molecular orbitals from d orbitals

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In transition metals and other heavier elements, the \(d\) orbitals may combine with other orbitals of compatible symmetry (and energy) to form molecular orbitals. Generally, there are three types of bonding and antibonding interactions that may occur with \(d\) orbitals: sigma (\(\sigma\)), pi (\(\pi\)), and delta (\(\delta\)) bonds.

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Cool example of a pi bond without an accompanying sigma bond in a silicon-based compound!

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Cool example of a pi bond without an accompanying sigma bond in a silicon-based compound!

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New silicon–silicon bond is a rare example of a π bond without a σ bond

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Discovery made in silicon analogue of bicyclobutane

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Can a quadruple bond exist? It's quite rare for atoms in the s- and p-blocks of the periodic table, but here's a relatively recently discovered example!

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Can a quadruple bond exist? It's quite rare for atoms in the s- and p-blocks of the periodic table, but here's a relatively recently discovered example!

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When it comes to extreme multiple bonds, the transition metals have long ruled the roost. Quadruple bonds? They've got thousands of them. Quintuple bonds? Right there in a landmark organometallic dichromium complex made in 2005. Even sextuple bonds have been found, in Mo ₂ and W ₂.

Molecular orbitals for the two sigma and two pi bonds in diatomic rhodium boride
These molecular orbitals (purple and silver) show the two sigma bonds and two pi bonds that make up the quadruple bond in RhB (aquamarine = Rh, pink = B). Credit: J. Phys. Chem. Lett.

In contrast, the main-group elements-those in the s- and p-blocks of the periodic table-have lagged behind in the multiple-bonding stakes. But now Lai-Sheng Wang and colleagues at Brown University have defied expectations by reporting that diatomic rhodium boride (RhB) contains a quadruple bond ( J. Phys. Chem. Lett. 2020, DOI: 10.1021/acs.jpclett.9b03484).

Main-group elements are generally thought to max out at triple bonds because of the number and geometry of orbitals they can use for bonding. In 2012, researchers calculated that diatomic C ₂ could contain a quadruple bond, but the claim was controversial because it invoked a weak bonding interaction between electrons on opposite sides of the molecule in orbitals that pointed directly away from each other. And whereas a quadruple bond should be stronger than a triple bond between the same atoms, calculations suggested that the connection in C2 was actually weaker than the triple bond in ethyne (C ₂H ₂).

Wang's team stumbled on boron's quadruple bond by accident. A few years ago the researchers made a compound containing a triple bond between bismuth and boron, and wondered if they could swap bismuth for a transition metal. They started their search with rhodium, largely because it only has one naturally occurring isotope, which makes it easier to work with experimentally and computationally.

So they fired a laser at a disk containing powdered rhodium and boron to produce a stream of vaporized compounds, and separated them in a mass spectrometer. Then they studied selected compounds by photoelectron spectroscopy, which measures the kinetic energies of electrons ejected from ionized samples and serves as a fingerprint of the structure and bonding in the molecules.

This process allowed the researchers to identify two curious compounds: a boronyl-coordinated rhodium boride, RhB(BO⁻), and RhB itself. The vibrational frequency of RhB suggests that its bond is shorter and stronger than the triple bond in its protonated form, RhBH⁺. The team also used theoretical calculations to study how the orbitals of each atom in RhB overlapped to form molecular orbitals. This showed that the atoms were connected by two sigma bonds and two pi bonds.

Taken together, Wang says, all their evidence suggests that RhB is the first diatomic molecule containing a quadruple bond to a boron atom. "Next time I teach a physical chemistry class, this will change how I lecture about the chemical bond," he says.

RhB is not a new molecule, though. It was made more than a decade ago ( Mol. Phys. 2007, DOI: 10.1080/00268970701390172), and was regarded as triply bonded. This was because researchers assumed that one of the sigma-bonding molecular orbitals was a non-bonding lone pair on the boron atom, Wang says.

"It's definitely the most strongly bound of all the transition metal borides, based on our own results, so that's consistent with the quadruple bond," says Michael D. Morse at the University of Utah, who has previously worked with RhB. "I think their interpretation makes sense."

Overcoming preconceptions about RhB's triple bond was a big challenge, adds Wang, and their paper was submitted to several journals before it was finally published. "I have never had an article with so many reviewers," he says. That delay meant they were unable to claim the first ever quadruple bond to boron-another team reported quadruple bonding in BFe(CO) ₃⁻ late last year ( Nat. Commun. 2019, DOI: 10.1038/s41467-019-12767-5). "In science, you win some, you lose some," Wang says.

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RhB is the first diatomic molecule with a four-fold bond to boron

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Great questions during today's class! Here's a short video from recent Nobel Prize winner Carolyn Bertozzi explaining the chemistry behind why neuraminidase inhibitors (such as Tamiflu) work as flu drugs.

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Great questions during today's class! Here's a short video from recent Nobel Prize winner Carolyn Bertozzi explaining the chemistry behind why neuraminidase inhibitors (such as Tamiflu) work as flu drugs.

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Tamiflu and Relenza - Carolyn Bertozzi (Berkeley/HHMI)

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Researchers analyzed 25,000 natural adhesives to understand what makes a strong glue. Based on this they created new formulations that are stronger than any similar substances found in nature.

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Researchers analyzed 25,000 natural adhesives to understand what makes a strong glue. Based on this they created new formulations that are stronger than any similar substances found in nature.

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New adhesive is so sticky it can glue a rubber duck to a seaside rock

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Features of 25,000 biological adhesives analysed to create glues stronger than any found in nature

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A circular molecule made up of just 48 carbons has been stabilized using macrocycles. This has allowed this kind of normally fleeting carbon allotrope to be bottled and investigated.

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A circular molecule made up of just 48 carbons has been stabilized using macrocycles. This has allowed this kind of normally fleeting carbon allotrope to be bottled and investigated.

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Ring of pure carbon stabilised by its catenane connections

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C48 carbon allotrope can be isolated in solution

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Usinic acid is everywhere, from city streets to rock faces. It could have medical and cosmetic uses, if its toxicity can be overcome.

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Usinic acid is everywhere, from city streets to rock faces. It could have medical and cosmetic uses, if its toxicity can be overcome.

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Exploring the potential uses of usnic acid

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As well as protecting lichen, this compound could have medical and cosmetic applications - if toxicity concerns can be overcome

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Antibiotics designed with the help of AI attack bacteria in entirely new ways

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Two new compounds display potent activity against deadly drug-resistant bacteria