Chemical Communications Blog

 A team in the US has shown that enantiopure and racemic crystals can be separated by magnetic levitation.

A rotaxane is a mechanically-interlocked molecule that consists of one or more rings trapped on a linear unit, the thread, by two bulky constituents, the stoppers. Remarkably, the ring components are not covalently attached to the dumbell component, rather a mechanical bond is present that intrinsically links the components of the molecule and prevents their dissociation without the cleavage of one, or more, covalent bonds. The synthesis of these interlocked molecules is of much interest to chemists today as a means of not only synthetically mimicking molecular geometries found in nature, but also, and perhaps more interestingly, as a means of exploiting the emergent properties imparted as a result of the mechanical bond for function as catalysts, motors and sensors, to name but a few examples.

The synthesis of rotaxanes is analogous to Goldilock’s quest to find the perfect bowl of porridge or the bed that is just right – finding the correctly-sized macrocycle to thread a rotaxane dumbbell is also a game of too big, too small or just right. Historically speaking, many of the rotaxanes reported thus far achieve “just right” by providing a steric bulk to the dethreading of the two components by simply increasing the size of the rotaxane stoppers. This is a valid approach, however it would also be advantageous in terms of synthetic ease and the possibility of introducing diversity to the rotaxane library if we could move away from big macrocycles and the necessary bulky stoppers, to smaller stoppers that allow for much smaller macrocycles.

But – how small is too small? Sometimes a macrocycle is just not big enough. Steve Moratti and James Crowley of the University of Otago, and coincidentally where i began my foray into chemistry, have set out to study just this – what is the smallest macrocycle that can be incorporated into a [2]rotaxane synthesized using the highly efficient Cu(I)-catalyzed Huigsen 1,3-dipolar cycloaddition active metal template approach developed by the Leigh group( JACS, DOI:10.1021/JA056903F).

To date, the smallest macrocycle that has been utilized in the synthesis of such rotaxanes is a 26-membered ring that generates [2]rotaxanes in high yields (DOI; 10.002/ANIE.201100415). Moratti and Crowley took this exploration a step further and studied the possibility of rotaxanation using even smaller 22- and 24-membered rings. One of the biggest advantages of moving towards smaller rotaxanes is the greater ability with which they can be functionalized over their larger analogues. Smaller macrocycles and less chemically-complicated stopper groups can be functionalized much more readily, as demonstrated in this work by the incorporation of a free hydroxymethyl group into the macrocycle and the use of unfunctionalized phenyl groups in the stopper components.

This study determined that the limit for rotaxanation was the larger of the two rings, with a [2]rotaxane forming in 70% yield –  read the article in full for free* to find out more!

CuAAC “click” active-template synthesis of functionalised [2]rotaxanes using small exo-substituted macrocycles: how small is too small?
Asif Noor, Warrick K. C. Lo, Stephen C. Moratti and James D. Crowley
DOI: 10.1039/C4CC03077J

You may also like to have a look at this Feature Article by Edward Neal and Stephen Goldup* from Queen Mary University, which reviews some of the less discussed consequences of mechanical bonding for the chemical behaviour of rotaxanes, and their application in synthesis

*Access is free through a registered RSC account – click here to register

About the web writer

Anthea Blackburn is a guest web writer for Chemical Science. Anthea is a graduate student hailing from New Zealand, studying at Northwestern University in the US under the tutelage of Prof. Fraser Stoddart (a Scot), where she is exploiting supramolecular chemistry to develop multidimensional systems and study the emergent properties that arise in these superstructures. When time and money allow, she is ambitiously attempting to visit all 50 US states before graduation.

This ChemComm Feature Article by Chuo Chen’s group, based at the Southwestern Medical Center, University of Texas focuses on biosynthesis and total synthesis of cyclic pyrrole-imidazole dimers. Pyrrole-imidazole alkaloids are secondary metabolites which are found exclusively in marine sponges. They have very unique structures and attractive biological properties. Part of what makes these molecules so interesting is the fact that they contain many functional groups and are highly populated with nitrogen atoms. Pyrrole-imidazole alkaloids often have polycyclic skeletons which make them ideal platforms to work on in the development of new synthetic ideas and methodologies.

Many pyrrole-imidazole alkaloids have been tested and determined to have promising biological properties such as anticancer, antimicrobial, antiviral or immunosuppressive activities. Although this is the case, much work still needs to be carried out to determine the full biological profile of pyrrole-imidazole alkaloids.

Another aspect of pyrrole-imidazole alkaloids which still contains unknowns is the biosynthetic pathway; a range of biosynthetic pathways have been suggested but the complete route has not yet been fully determined. It is agreed that the main stages of the biosynthesis are catalysed by cyclases and oxidases but the exact enzymes have not been identified. A number of interesting hypotheses are highlighted and discussed in this review including work from Faulkner and Clardy who isolated the first dimeric pyrrole-imidazole alkaloid, sceptrin, in 1981.

As well as summarising different biosynthetic routes to these intriguing compounds the authors also discuss synthetic strategies. Numerous groups have successfully synthesised different pyrrole-imidazole dimers and highlights of this section include Baran’s work synthesising a number of different dimers and Chen’s own work which involves developing a biomimetic approach for the synthesis of ageliferins. Chen’s synthesis contains an oxidative radical cyclisation as the key step to give the ageliferin core skeleton. The group have successfully synthesised a range of ageliferins using this adaptable approach.

To download the full article for free* click the link below:

Dimeric pyrrole-imidazole alkaloids: synthetic approaches and biosynthetic hypotheses
Xiao Wang, Zhiqiang Ma, Xiaolei Wang, Saptarshi De, Yuyong Ma and Chuo Chen
DOI: 10.1039/c4cc02290d

*Access is free until the 12.07.14 through a registered RSC account – click here to register

A compound that kills bacteria and cleaves their DNA to prevent them passing on drug-resistant genes has been designed by researchers in India.

The increasing ineffectiveness of antibiotics and the absence of suitable new ones are problems long recognised by the medical community. Bacteria can mutate and adapt to become resistant so the stock of effective antibiotics is diminishing. In a recent report, the UK’s Chief Medical Officer stated that increasingly resistant microbes represent a global threat that in the next 20 years could see many more deaths associated with what were routine and safe surgeries.

Read the full article in Chemistry World»

Read the original journal article in ChemComm – it’s free to download until 11th July:
A prospective antibacterial for drug-resistant pathogens: a dual warhead amphiphile designed to track interactions and kill pathogenic bacteria by membrane damage and cellular DNA cleavage
Durairaj Thiyagarajan, Sudeep Goswami, Chirantan Kar, Gopal Das and Aiyagari Ramesh
Chem. Commun., 2014, Advance Article, DOI: 10.1039/C4CC02354D, Communication