Organic & Biomolecular Chemistry Blog

In this PERSPECTIVE article, Marco Bandini presents an overview of indole electrophilicity, illustrated with a range of pertinent examples of this “dark-side” of indole reactivity.

Indoles are one of the most common heterocyclic motifs found in nature. These bicyclic arenes have had a profound impact on drug discovery, materials science, catalysis and many other areas of chemistry.

Professor Marco Bandini and his research group at the Università di Bologna specialise in indole “decoration” and the development of new methodology for the chemical manipulation of this functional group.

The indolyl core is, as Bandini explains, “spectacularly nucleophilic” and this accounts for a large proportion of the literature contributions. There is, however, also a relatively undeveloped side of their reactivity: “electrophilic” indoles.

While there are many examples of this type of reactivity, some of which date back to the 1960s, it remains in the shadow of the well-understood and established chemistry that explores the indole core’s innate nucleophilicity. The opportunities to expand the chemical portfolio of indole decoration, via nucleophilic substitutions and additions, are still largely unexplored.

The ubiquity of this core means that new ways to functionalise and manipulate indoles will always be a welcome addition to the organic chemist’s toolbox. As Bandini discusses, exploitation of the umpolung chemistry of these functional groups provides access to a wide diversity of chemical structures.

This Perspective article elegantly documents the electrophilic nature of indoles, and highlights some of the important discoveries and developments in this field. It is a must-read for anyone interested in these intriguing molecules.

Give yourself to the dark side and check out the article here.

Electrophilicity: the “dark-side” of indole chemistry
Marco Bandini
DOI: 10.1039/C3OB40735G

In this HOT article, Julius Rebek Jr presents a fascinating insight into the design of molecules which can detect and destroy organophosphorus compounds.

Organophosphorus (OP) compounds are primarily used as pesticides, and can be a useful alternative to more traditional chlorinated hydrocarbon-based pesticides. However, due to OP compounds’ ability to inhibit acetylcholine esterase (AChE), they can be extremely toxic to humans and they have therefore found use as nerve agents and chemical weapons. For these reasons, their toxicity is an area of intense research focus and new methods for their detection and treatment are always welcome.

Rebek and his research group at The Scripps Research Institute have been looking into molecular sensors for OPs for several years, and this paper highlights some of the significant developments in the field. Their interest in the area was sparked by a carefully crafted pyridine structure discovered by Swager, which upon reaction with an OP undergoes a subsequent cyclisation reaction to create a fluorescent dye. This is a useful premise for the sensing of OPs. The Rebek group have expanded upon this premise and developed a series of molecular sensors that employ similar mechanisms. They have used their established expertise in cavitand chemistry to develop specially-tailored vase-shaped molecules, which are able to fold around OP-based nerve agents and isolate them from the surrounding medium. This paper provides a whistle-stop tour of an exciting and important area of organic chemistry.

Chemical approaches for detection and destruction of nerve agents
Dariush Ajami and Julius Rebek, Jr.
DOI: 10.1039/c3ob40324f

Free to access for 4 weeks

One of the essential capabilities of bacteria for their continued survival is the ability to adapt and change to reflect the changing environment in which they reside. One way in which they achieve this is through the second messenger signalling molecule bis-(3′–5′)-cyclic dimeric guanosine monophosphate (c-di-GMP), which facilitates behaviour adaptions.

c-di-GMP is found throughout the bacterial domain and plays a vital role in regulating the transition between the motile planktonic lifestyle and the sessile biofilm forming state. It also controls the virulence response of pathogenic organisms and is thought to be connected to quorum sensing, the process by which bacteria communicate with each other.

This HOT review from Scott A. Strobel and Carly A. Shanahan, Yale University, summarises the current state of knowledge and understanding of c-di-GMP signalling in bacteria with a focus on protein and RNA binding partners of the second messenger. Efforts towards the synthesis of c-di-GMP and its analogues are discussed as well as studies aimed at targeting these binding partners with synthetic dinucleotide analogues.

To find out more about this messenger molecule read this review taken from our Nucleic acids: new life, new materials collection.

Enjoy free access for 4 weeks, so download it today.

The bacterial second messenger c-di-GMP: probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs
Carly A. Shanahan and Scott A. Strobel
DOI: 10.1039/C2OB26724A

Electrophilic cyclisations is an area of chemistry that is continually and rapidly growing and expanding. This Emerging area from Adeline Palisse and Stefan F. Kirsch, University of Wuppertal, highlights the recent progress in C–C bond-forming halocyclisations allowing the reaction of alkynes with carbon-nucleophiles.

Palisse and Kirsch focus on iodine electrophiles, and aim to show that these iodocyclisations with alkynes have become a very useful strategy to construct structures.  The review is roughly split into three major categories:
1)    malonates as nucleophilic
2)    arene nucleophiles
3)    olefins as nucleophiles

Read this Emerging Area today! Download it free by following the link below…

Metal-free reactions of alkynes via electrophilic iodocarbocyclizations
Adeline Palisse and Stefan F. Kirsch
DOI: 10.1039/C2OB26508G

This HOT review from Christian Melander and colleagues at North Carolina State University presents a comprehensive overview of development of small molecules targeting bacterial biofilms through non-microbicidal mechanisms. Melander et al. discuss the varied approaches that are applied to the discovery of lead small molecules that mediate the development of biofilms. These are grouped as:

• Compounds that modulate biofilms by targeting bacterial signalling pathways
• Chemical library screening
• Natural products and natural product analogues that possess anti-biofilm activity

This review is very timely and covers an important topic in addressing bacterial infections, as antibiotic resistance is an issue of ever increasing concern, and has been described as a must read.

Download it today by following the link below; it’s free to access for 4 weeks

Small molecule control of bacterial biofilms
Roberta J. Worthington, Justin J. Richards and Christian Melander
DOI: 10.1039/C2OB25835H