RSC Advances Blog

We are very pleased to introduce Pavel Bobal, Jan Otevrel and David Svestka, the authors of the paper ‘One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles‘. Their article has been very well received and handpicked by our reviewers and handling editors as one of our HOT articles.  The team told us more about the work that went into this article and what they hope to achieve in the future. You can find out more about the authors and their article below and find more HOT articles in our online collection.

Meet the Authors

	Pavel Bobal studied organic chemistry at Slovak Technical University, Bratislava, Slovakia, where he received his doctoral degree in 1996. He spent 3 years between 1995 and 1998 as a postdoc at the University of Neuchatel, Switzerland (Prof. Neier) and additional 3 years at the University of Nevada, Reno, USA (Prof. Lightner). From 2001 to 2009 he worked in the pharmaceutical industry (R&D). In 2009 he became an assistant professor and then in 2019 an associate professor at Faculty of Pharmacy, UVPS Brno, Czech Republic. Since 2020 this faculty has been reestablished as a part of Masaryk University, Brno, Czech Republic.
	Jan Otevrel was a former Ph.D. student of Pavel Bobal, he received his doctoral degree in 2017 and then became an assistant professor at the same university. During his Ph.D. he spent 3 months at Justus Liebig University, Giessen, Germany (Prof. Hrdina) and he will soon (this year) start a postdoc position at Johannes Kepler University, Linz, Austria (Prof. Waser). He has discovered and co-developed the process published in the current study.
	David Svestka received his master’s degree in 2019 at UVPS Brno, Czech Republic. He is currently a Ph.D. student in the Pavel Bobal’s laboratory and participated in the development of the present method.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Our paper describes a new method for synthesis of vicinal amino alcohols from the respective amides or nitriles by a simple set of reaction conditions. Amino alcohols are compounds of high interest in many branches of chemistry.

How big an impact could your results potentially have?
It is always hard to predict feedback of the scientific article. However, from our perspective, we would be glad if the developed process will find place in syntheses of vicinal amino alcohols conducted at research laboratories and if the readers of RSC Advances will appreciate efforts which we have invested in this paper.

Could you explain the motivation behind this study?
Due to our continuous interest in the organocatalyzed aldol-type reactions, we have been exploring syntheses of numerous chiral auxiliaries for the catalyst design and screening. These long-term endeavor paved a way for our current unexpected discovery.

In your opinion, what are the key design considerations for your study?
The key consideration in this study is to use an old and well-known reagent in a new context to reveal the novel and yet unexplored reactivity.

Which part of the work towards this paper proved to be most challenging?
The methodological articles in organic synthesis usually share the common structure such as the optimization section, determination of the substrate scope, and a relevant synthetic application of the method. Thus from the initial interesting observation, it is often quite a long journey towards the good scientific paper. Honestly, one of the most challenging parts of the above article was to establish a plausible mechanism of the reaction and to support it with enough evidence.

What aspect of your work are you most excited about at the moment?
One of the most exciting moments of this discovery was to figure out that benzylic oxidation can occur even under reduction conditions, which is somewhat counter-intuitive. Indeed, sodium bis(methoxyethoxy)aluminum hydride gave us a great lecture that more than 50 years old and almost comprehensively explored reagent is still able to surprise.

What is the next step? What work is planned?
We will continue with our work in organic synthesis and medicinal chemistry and we will look forward to the new and especially the unexpected chemical discoveries.

One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles
Jan Otevrel, David Svestka and Pavel Bobal
RSC Adv., 2020,10, 25029-25045
DOI: 10.1039/D0RA04359A, Paper

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We are very pleased to introduce Saurabh Das, the corresponding author of the paper ‘A Zn^II complex of ornidazole with decreased nitro radical anions that is still highly active on Entamoeba histolytica‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our June HOT articles.  Saurabh was kind enough to tell us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and their article below and find more HOT articles in our online collection.

Meet the Author

Saurabh Das completed his bachelor’s degree with honours in Chemistry from Presidency College in 1990, then affiliated to University of Calcutta. His Master’s with specialization in Inorganic Chemistry was done at the University College of Science, University of Calcutta in 1992. He received his PhD from University of Calcutta in 2000 having worked at the Chemical Sciences Division of Saha Institute of Nuclear Physics (Ph D Supervisor: Prof. Parikshit C Mandal). After two years of teaching at the Calcutta International School, Kolkata (1998-2000), five and a half years of teaching at the Department of Chemistry, Bejoy Narayan Mahavidyalaya, Hooghly (under University of Burdwan) (2000-2006) he joined the Department of Chemistry, Jadavpur University in January, 2006.

He is now a Professor with research interests in modulating the generation of reactive intermediates of different drugs forming inorganic complexes to strike a balance between efficacy and adverse effects; and offshoots of that general theme. He has 66 publications in peer reviewed international journals.

The research team:

Ms Neha Banyal (left photo) and Professor Kasturi Mukhopadhyay (right photo)

Professor Saurabh Das and Ms Promita Nandy (left photo) and Professor Sanjay Kumar and Mr Soumen Singha (right photo)

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
The molecule (Ornidazole) is a drug belonging to the 5-nitroimidazole family that is used to treat bacterial and/or parasitic infections. The performance of the drug depends on the generation of an intermediate (the nitro radical-anion) that kills disease causing microbes. The same intermediate is neurotoxic to the host (i.e. the system affected by disease causing microbes) upon prolonged use. Hence, controlling the generation of the nitro-radical anion is essential to strike a balance between efficacy and neurotoxic side effects.

How big an impact could your results potentially have?
The results should have a good impact since we worked with a compound that is already established as a drug and is part of a number of pharmaceutical formulations. The modified compound, i. e. the zinc complex needs to be tried in vivo, in living systems in order to identify the extent of difference between the work performed by in the laboratory (on model systems) and what the results would be on living systems. Experts would understand and realize here that a certain difference would exist which needs to be identified.

Could you explain the motivation behind this study?
The motivation of the study was to strike a balance between efficacy and neurotoxic side effects for this family of drugs. For most drugs, intermediates involved with the drug’s efficacy are its problems as well. If they can be separated, then one can either increase cure for an accepted level of complication or decrease complications for an accepted level of cure.

In your opinion, what are the key design considerations for your study?
Modification of Ornidazole (the drug) in a manner that generation of nitro-radical anion is controlled, i.e, modulated. For our study, this was achieved through complex formation with Zn(II).

Which part of the work towards this paper proved to be most challenging?
There were three aspects to the study i) preparation of the complex and its characterization,, ii) showing that generation of nitro-radical anion is less for the complex which we followed by an enzyme assay and iii) inspite of decrease in nitro-radical anion formation, the complex showed the same efficacy on amoeba, as that observed for Ornidazole. A combination of these three aspects performed through suitable experiments suggest decrease in the formation of the nitro radical-anion should decrease neurotoxicity on the host (although we did not verify this in our study) but it should happen since studies earlier to ours have linked neurotoxicity to nitro radical-anion formation. Simultaneously, bacteria or parasite killing should also be affected which in our case did not happen. The complex maintained its killing efficacy of amoeba even with decreased nitro radical-anion; being as good as Ornidazole. This we attributed to aspects related to complex formation. We showed one such attribute of the complex in our study, that of it being able to bind DNA better than Ornidazole. So it’s really a culmination of different experiments we performed.

What aspect of your work are you most excited about at the moment?
The fact modification of Ornidazole through complex formation with Zn(II) could increase its therapeutic index (T I) where T I = TD₅₀/ED₅₀; TD₅₀ implies toxic dose in 50% of subjects and ED₅₀ implies effective dose for 50% of population. The larger the T I, safer the drug. Besides, Zn being relatively non-toxic unlike other metal ions and since there is use for it in the bio-system, it should not be harmful if it goes into our bodies

What is the next step? What work is planned?
I have not really thought about it. Since the manuscript has been well received I will have to speak to one of my collaborators (Prof. Kasturi Mukhopadhyay of School of Environmental Sciences at the Jawaharlal Nehru University, New Delhi) in whose laboratory the biological experiments were performed, if she could take the Zn(II) complex forward and do few more studies with it that reveal its mechanism of action on bacteria and amoeba strains; may be try on different bacterial strains, while we perform more model studies to search for other attributes of complex formation. After these are done a sharing of data on biological experiments for mechanism of action and model studies performed (by us) could be useful to see for ourselves whether they correct to each other or establish a difference of opinion.

A Zn^II complex of ornidazole with decreased nitro radical anions that is still highly active on Entamoeba histolytica
Promita Nandy, Soumen Singha, Neha Banyal, Sanjay Kumar, Kasturi Mukhopadhyay and Saurabh Das
RSC Adv., 2020,10, 23286-23296
DOI: 10.1039/D0RA02597F, Paper

Submit to RSC Advances today! Check out our author guidelines for information on our article types or find out more about the advantages of publishing in a Royal Society of Chemistry journal.

Keep up to date with our latest HOT articles, Reviews, Collections & more by following us on Twitter. You can also keep informed by signing up to our E-Alerts.