Organic & Biomolecular Chemistry Blog

The C8 position of guanine is known to be vulnerable to forming adducts that cause damage to DNA,  and these adducts are often used as biomarkers to indicate conditions such as oxidative stress.  Forming guanine adducts synthetically usually occurs via Pd-catalysed coupling reactions, as radical-based approaches generally have poor yields.  Water has also seldom been used as a reaction medium, despite its relevance to biomimetic chemistry.

However, this HOT article from Chryssostomos Chatgilialoglu et al. describes the successful radical-based alkylation of two guanine derivatives in aqueous solution via γ-radiolysis.  The mechanism of α-hydroxylalkyl radical addition to the C8 position of the purine ring, which results in intermolecular C-C bond formation, is discussed in detail and provides useful  insights into the radical chemistry of 8-bromoguanines.

This paper is free to access until 26th April and is part of the forthcoming OBC special web themed issue on radical chemistry.

Radical-based alkylation of guanine derivatives in aqueous medium
Chryssostomos Chatgilialoglu, Clara Caminal and Quinto G. Mulazzani
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01264E

Alterations in fluid viscosity at the cellular and organismal level can lead to different disorders and diseases such as Alzheimer’s, diabetes, hypertension, infarction and others. This is why, in recent years, there has been an increasing interest in the development of new methods to measure fluid viscosity.

Scientists at University of California, San Diego, and University of Georgia have now developed self-calibrating fluorescent sensors that can be used  for ratiometric measurements of viscosity by covalent linking a reference fluorophore (donor) with a molecular rotor (acceptor). They also present an application of these dyes for the detection of changes of the membrane viscosity in a liposome model and they show that shorter linker length produces a more viscosity sensitive dye.

You can now read this HOT article which is free to access until 26th April. Both the referees and the Editorial Office ranked it as very significant.

Synthesis and evaluation of self-calibrating ratiometric viscosity sensors
Hyung-Jo Yoon, Marianna Dakanali, Darcy Lichlyter, Willy M. Chang, Karen A. Nguyen, Matthew E. Nipper, Mark A. Haidekker and Emmanuel A. Theodorakis
Org. Biomol. Chem.
DOI: 10.1039/C0OB01042A

Read the latest OBC hot paper in which Thorsten Bach and colleagues use a hydrogen bond template to carry out highly enantioselective radical cyclisations.

Bach’s template works as a steric shield preventing the approach of a reagent from one side of the molecule. Using the method Bach was able to demonstrate radical cyclisations of quinolines with 94–99% ee.

This is an important investigation with wide reaching consequences and will be of interest to many organic chemists. Its free to download until 21^st April.   

This paper will be  included in the OBC special web themed issue on radical chemistry that will be published soon. Keep an eye on it!

Enantioselective radical cyclisation reactions of 4-substituted quinolones mediated by a chiral template
Aline Bakowski, Martina Dressel, Andreas Bauer and Thorsten Bach
Org. Biomol. Chem., 2011, DOI: 10.1039/C0OB01272F

Terpenes and other polycycles are very common in nature and as many are biologically active, have been a key target for synthetic organic chemists. Rama Heng and Samir Zard from Ecole Polytechnique in France have demonstrated a general approach to polycyclic structures featuring the direct formation of six-, seven-, and eight-membered rings. This very powerful, yet concise and highly flexible, approach to both fused and bridged polycyclic structures overcomes the limitations imposed by intrinsically slow radical transformations, opening numerous synthetic opportunities. Our referees were very enthusiastic about this paper and we think you will be too – expect to see more about this exciting new method!

This HOT article is available free until 21st April 2011! Read it today in OBC.

A flexible, unified radical-based approach to polycyclic structures
Rama Heng and Samir Z. Zard
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C1OB00024A

Researchers from Kaohsiung Medical University, Taiwan, have synthesised and tested a number of 2,3-diarylquinoline derivatives for anticancer activities, one of which showed significant potential preventing cell growth in certain cancer cell lines.

Cherng-Chyi Tzeng and colleagues synthesised the 2,3-diarylquinoline derivatives as part of a continuing study to explore potent anticancer drug candidates.  The quinoline skeleton is prevalent in many natural and synthetic heterocycles with a wide range of biological effects, including antitumor activity.  The structures of tamoxifen and combretastatin A-4, two potent anticancer agents, were modified to include the quinoline moiety and various side chains to improve their activity.

Testing against six cancer cell lines, including human hepatocelluar carcinoma, non-small cell lung cancer and breast cancer, revealed one compound that was more active than tamoxifen.  6-fluoro-2,3-bis{4-[2-(piperidin-1-yl)ethoxy]phenyl}quinoline-otherwise known in this paper as the more manageable 16b-was shown to induce cell cycle arrest at the G2/M phase, resulting ultimately in cell death in half of the tested cell lines.  Work is ongoing to optimise the structure.

This HOT article is free to access for the next month – download it today!

Synthesis and antiproliferative evaluation of 2,3-diarylquinoline derivatives
Chih-Hua Tseng, Yeh-Long Chen, Kuin-Yu Chung, Chi-Huei Wang, Shin-I Peng, Chih-Mei Cheng and Cherng-Chyi Tzeng
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01225D

Although the presence of ozone and NO_x gases (i.e. NO^. and NO₂^.) are often linked to an increase in respiratory conditions such as asthma, the mechanism by which these pollutants cause respiratory distress is still not clear. Interestingly, the highly reactive NO₃^. (formed in the atmosphere at night by reaction of O₃ and NO₂^.) has been somewhat overlooked as a possible respiratory irritant despite numerous studies on its role in the atmosphere.

In this HOT paper Uta Wille and colleagues at the University of Melbourne follow up a previous study published in Chem. Comm. which identified the products of the reaction of the NO₃ radical with amino acids.  Now, they have simulated the exposure of proteins present at the surface of the respiratory tract to a number of environmental pollutants, determining clear reaction pathways resulting in aromatic ring nitration of the amino acids studied.  They note that nitrated aromatic amino acids are often observed in a wide range of inflammatory-immune responses such as asthma and cystic fibrosis, leading them to suggest that the NO₃ radical could actually be the real culprit in certain pollution-related diseases.

You can read the full details of this interesting study online here (it’s free to access for the next month!).

This paper is included in the OBC special we themed issue on radical chemistry that will be published soon. Keep an eye on it!

Damage of aromatic amino acids by the atmospheric free radical oxidant NO3˙ in the presence of NO2˙, N2O4, O3 and O2
Catrin Goeschen, Natalia Wibowo, Jonathan M. White and Uta Wille
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB01186J

And the previous Chem. Comm. paper can be found here:

Can the night-time atmospheric oxidant NO3˙damage aromatic amino acids?
Duanne C. E. Sigmund and Uta Wille
Chem. Commun., 2008, 2121-2123
DOI: 10.1039/B803456G