Institute Of Organic Chemistry Research Articles

Preface

The International Conference Kliment’s days 2023 (KD2023) is a notable event held from 9-11 November 2023 in Sofia, Bulgaria. The annual scientific conference is organised by the Faculty of Biology, Sofia University “St. Kliment Ohridski”. KD2023 served as a platform for the exchange of knowledge, sharing experiences, and fostering collaboration on innovative approaches within the fields of Biodiversity and Biological Education, Molecular Biology and Biotechnology, and Ecology and Sustainable Development. The conference featured a plenary session during which esteemed speakers present the following plenary lectures:• Boris Kryštufek, Slovenian Museum of Natural History, Ljubljana, Slovenia, Back to the future: reemergence of natural history.• Ariola Bacu, Department of Biotechnology, Faculty of Natural Sciences, University of Tirana, Albania, Biological indicators & single-cell cytotoxicity sensing - lessons learned on the quality of waters.• Adele Muscolo, Department of Agraria, “Mediterranean” University, Reggio Calabria, Italy, Fertilizer produced with wastes modulates antioxidant compounds and activities in tomato.• Ioannis P. Gerothanassis, Section of Organic Chemistry & Biochemistry, Department of Chemistry, University of Ioannina, Greece, Ligand-observed NMR: principles and applications in the field of biocatalysed reactions, ligand-macromolecular interactions and investigations at the cellular level.• Miodrag Stojkovic, SPEBO Medical, Leskovac, Serbia, Human pluripotent stem cells – a unique tool to decipher specific cell responses, diseases, and biomarkers.• Antoaneta Trendafilova, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria, Secondary metabolites in Inula species from the Bulgarian flora and biotechnological approaches for their accumulation (as part of the Satellite Scientific Symposium “Medicinal and Aromatic Plants for Innovative Bioactive Products - MAPBIO”).A total of 148 participants actively engaged in KD2023, which included the parallel Satellite Scientific Symposium (MAPBIO). In addition to the plenary lectures, the conference featured 16 oral presentations delivered by a diverse group comprising four foreign authors, twelve Bulgarian authors, including five young scientists and PhD students. During the poster session, over 112 poster presentations were presented with over 200 participants, encompassing 15 foreign authors and 76 young scientists, students and PhD students. Additional information about the KD2023, including program, book of abstracts, etc. can be found on the official website of the conference: https://www.biofac.info.The successful execution of KD2023 was made possible through the support of the University Science Fund, as well as the dedicated efforts of the scientific and organizing committee. The active involvement of student volunteers in the event, along with the contributions of all third parties, played a crucial role in ensuring the event’s success.We are delighted to note the widespread resonance of the event within the scientific community, drawing participants from a diverse range of countries, including Albania, Slovenia, Greece, Italy, the Republic of Kosovo, the Republic of North Macedonia, Serbia, Türkiye, etc. The conference also attracted participants from various Universities and institutions in Bulgaria.The use of the Morressier platform facilitated a seamless reviewing process, showcasing the responsive collaboration between the editorial team, reviewers, participants, and the Morressier team.List of Editors, Conference Committee are available in this Pdf.

Design and Photonics of Merocyanine Dyes.

Merocyanines, thanks to their easily adjustable electronic structure, appear to be the most versatile and promising functional dyes. Their D-π-A framework offers ample opportunities for custom design through variations in both donor/acceptor end-groups and the π-conjugated polymethine chain, and leads to a broad range of practical properties, including noticeable solvatochromism, high polarizability/hyperpolarizabilities, and the ability to sensitize various physicochemical processes. Accordingly, merocyanines are applied and extensively studied in various fields, such as light-converting materials for optoelectronics, nonlinear optics, optical storage, solar cells, fluorescent probes, and antitumor agents in photodynamic therapy. This review encompasses both classical and novel more important publications on the structure-property relationships in merocyanines, with particular emphasis on the results by A. I. Kiprianov and his followers in Institute of Organic Chemistry in Kyiv, Ukraine.

Highly Luminescent Blue Emitter with Balanced Hybridized Locally and Charge‐Transfer Excited‐States Emission

AbstractThe Front Cover image is provided by Julia Wiefermann, Institute of Organic Chemistry and Macromolecular Chemistry (HHU, Düsseldorf, Germany). The image shows the highly blue luminescent emitter 4’’‐(diphenylamino)‐2’’‐methyl‐[1,1’:4’,1’’‐terphenyl]‐4‐carbonitrile which exhibits balanced hybridized local and charge‐transfer (HLCT) excited state emission. This compound was successfully employed in an OLED device. Read the full text of the Research Article at 10.1002/cptc.202200265.

DISCLOSED INVENTIONS ON SCREENING TECHNOLOGIES OF SOLID, HOMOGENEOUS ROCKET PROPELLANT CHARGES

Results of search and analysis of Polish disclosed secret patents on screening (inhibiting) technology of solid, homogeneous rocket propellants, were presented. Due to search on this subject, seven inventions applied by Institute of Organic Chemistry as secret ones to the Polish Patent Office in years 1968-1980, were found. Pieces of information on their disclosure, i.e. about removing secrecy, were published in the News of the Patent Office issued in years 2007-2008.

Predicting for anti-(mutant) SARS-CoV-2 and anti-inflammation compounds of Lianhua Qingwen Capsules in treating COVID-19

BackgroundLianhua Qingwen Capsules (LHQW) is a traditional Chinese medicine prescription commonly used to treat viral influenza in China. There has been sufficient evidence that LHQW could effectively treat COVID-19. Nevertheless, the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds in LHQW are still vague.MethodsThe compounds of LHQW and targets were collected from TCMSP, TCMID, Shanghai Institute of Organic Chemistry of CAS database, and relevant literature. Autodock Vina was used to carry out molecular docking. The pkCSM platform to predict the relevant parameters of compound absorption in vivo. The protein–protein interaction (PPI) network was constructed by the STRING database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out by Database for Annotation, Visualization, and Integrated Discovery (DAVID). The anti-(mutant) SARS-CoV-2 and anti-inflammation networks were constructed on the Cytoscape platform.Results280 compounds, 16 targets related to SARS-CoV-2, and 54 targets related to cytokine storm were obtained by screening. The key pathways Toll-like receptor signaling, NOD-like receptor signal pathway, and Jak-STAT signaling pathway, and the core targets IL6 were obtained by PPI network and KEGG pathway enrichment analysis. The network analysis predicted and discussed the 16 main anti-SARS-CoV-2 active compounds and 12 main anti-inflammation active compounds. Ochnaflavone and Hypericin are potential anti-mutant virus compounds in LHQW.ConclusionsIn summary, this study explored the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds of LHQW against COVID-19, which can provide new ideas and valuable references for discovering active compounds in the treatment of COVID-19.

Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects.

Compounds with a phosphonate group, i.e., –P(O)(OH)2 group attached directly to the molecule via a P-C bond serve as suitable non-hydrolyzable phosphate mimics in various biomedical applications. In principle, they often inhibit enzymes utilizing various phosphates as substrates. In this review we focus mainly on biologically active phosphonates that originated from our institute (Institute of Organic Chemistry and Biochemistry in Prague); i.e., acyclic nucleoside phosphonates (ANPs, e.g., adefovir, tenofovir, and cidofovir) and derivatives of non-nucleoside phosphonates such as 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Principal strategies of their syntheses and modifications to prodrugs is reported. Besides clinically used ANP antivirals, a special attention is paid to new biologically active molecules with respect to emerging infections and arising resistance of many pathogens against standard treatments. These new structures include 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidines or so-called “open-ring” derivatives, acyclic nucleoside phosphonates with 5-azacytosine as a base moiety, side-chain fluorinated ANPs, aza/deazapurine ANPs. When transformed into an appropriate prodrug by derivatizing their charged functionalities, all these compounds show promising potential to become drug candidates for the treatment of viral infections. ANP prodrugs with suitable pharmacokinetics include amino acid phosphoramidates, pivaloyloxymethyl (POM) and isopropoxycarbonyloxymethyl (POC) esters, alkyl and alkoxyalkyl esters, salicylic esters, (methyl-2-oxo-1,3-dioxol-4-yl) methyl (ODOL) esters and peptidomimetic prodrugs. We also focus on the story of cytostatics related to 9-[2-(phosphonomethoxy)ethyl]guanine and its prodrugs which eventually led to development of the veterinary drug rabacfosadine. Various new ANP structures are also currently investigated as antiparasitics, especially antimalarial agents e.g., guanine and hypoxanthine derivatives with 2-(phosphonoethoxy)ethyl moiety, their thia-analogues and N-branched derivatives. In addition to ANPs and their analogs, we also describe prodrugs of 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a potent inhibitor of the enzyme glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA). Glutamate carboxypeptidase II inhibitors, including 2-PMPA have been found efficacious in various preclinical models of neurological disorders which are caused by glutamatergic excitotoxicity. Unfortunately its highly polar character and hence low bioavailability severely limits its potential for clinical use. To overcome this problem, various prodrug strategies have been used to mask carboxylates and/or phosphonate functionalities with pivaloyloxymethyl, POC, ODOL and alkyl esters. Chemistry and biological characterization led to identification of prodrugs with 44–80 fold greater oral bioavailability (tetra-ODOL-2-PMPA).

Neurohypophyseal Peptides from Prague and Swedish Laboratories Used as Pharmaceuticals. Part 2: Desmopressin, Terlipressin, Carbetocin – Pharmacology and Clinical Applications

Licence agreements between the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague (IOCB), and the pharmaceutical company Ferring AB Malmö enabled the Swedish company to produce and commercialize worldwide a number of neurohypophyseal peptides designed at the IOCB. Several of them found therapeutic applications.
 dDAVP: 1-deamino-8-ᴅ-arginine-vasopressin was designed in one of the IOCB peptide laboratories (M. Zaoral and F. Šorm) in 1967. It displayed an extremely high antidiuretic activity (various tests indicate a 2- to 50-fold increase, as compared to arginine vasopressin) and a very low pressor activity. The peptide (covered by the U.S. Patent No. 3,497,491, 1970) has been used as a preferred drug in the substitution therapy of the central form of diabetes insipidus (Minirin®, today as Desmopressin INN). Besides, as later discovered (Mannucci et al. 1977), dDAVP increases the plasma concentration of the blood-clotting factor VIII. This fact extended its clinical use as haemostatics in cases of milder forms of haemophilia A, von Willebrand-Jürgens syndrome and some thrombocyte dysfunctions. Despite of the clinical success of dDAVP, a closer look reveals certain inadequacies in the presently available pharmacological data: several reports declare activity values and the prolongation effect (index of persistence) in very broad ranges.
 Triglycyl-8-lysine-vasopressin (Terlipressin), a peptide with lysine vasopressin chain extended at the N‑terminal by a triglycine residue, acts mainly as a prodrug (releasing lysine vasopressin after aminopeptidase splitting at the Nα group). The analogue belongs to the so-called „synthetic hormonogens“; individual peptides carrying various acylating groups were synthesized in the mid-sixties at the IOCB and legally protected by U.S. Patent No. 3,558,590 (1968). It was a part of the licence agreements mentioned above. The activities of triglycyl-8-lysine-vasopressin (both antidiuretic and vasopressor) are about 100 times lower than those of lysine vasopressin, but its persistence is 5 times longer. As such, it is occasionally used in emergency medicine in cases of esophageal (and other gastroenteral) bleeding, traumatic or septic shock, in cirrhotic patients and patients with portal hypertension. Its use as an early abortion drug was discussed but not pursued.
 Carbetocin (deaminocarba1-2-O-methyltyrosin-oxytocin) was synthetized in the laboratory of Karel Jošt at the IOCB before 1971; its synthesis was covered by a Czechoslovak patent (CS-149,028 B1) in June 1973 (at that time, Czechoslovak patent law did not provide for the patentability of substances as such) and first published in a biophysical communication by Frič et al., 1974). As a part of the licence agreement, it was included in the production program of Ferring AB, but marketed later also by several other pharmaceutical companies due to an incomplete patent protection. The peptide is a moderately active uterotonic partial agonist and as such has been utilized in veterinary obstetrics for delivery induction in cows and (multiparous) pigs: its milder and better-controlled uterotonic action was found preferential as compared to oxytocin so far used for these purposes. In the last two decades, carbetocin has been commonly used also in the human obstetrics, especially to prevent the peri- and post-partum haemorrhage, from the maternal side the most frequent and most severe delivery complication. It became a life-saving drug in emergency obstetrics.

Efficient Synthetic Access to Novel Indolo[2,3-b]Quinoxaline-based Heterocycles.

This paper showed the synthetic capability of the indolo[2,3-b]quinoxaline nucleus to be provided as an excellent precursor for the synthesis of various heterocyclic compounds. These synthetic routes proceed via the formation of 3-(6H-indolo[2,3-b]quinoxalin-6-yl) propane hydrazide (2). The carbohydrazide 2 and its reactions with different reagents give five and six-membered rings, such as 1,3,4-thiadiazole, 1,3,4- oxadiazole, 1,2,4-triazole, and 1,2,4-triazine. All chemicals used in the current study were of analytical grade. Melting points were determined using an APP Digital ST 15 melting point apparatus and were uncorrected. FT-IR spectra were recorded on a Pye- Unicam SP3-100 and Shimadzu-408 spectrophotometers in KBr pellets and given in (cm-1) KBr. The NMR spectra were detected by a Bruker AV-400 spectrometer (400 MHz for 1H, 100 MHz for 1C and 40.55 MHz for 15N), Institute of Organic Chemistry, Karlsruhe, Germany. Chemical shifts were expressed as δ (ppm) with TMS as an internal reference. Mass spectrometry was provided on a Varian MAT 312 instrument in EI mode (70 eV). The target compounds were obtained, and their structures were completely elucidated by various spectral and elemental analyses (Ft-IR, 1H-NMR, 13;C-NMR, and mass spectrometry). The current work showed a view of the reactivity of the carbohydrazide group. The carbohydrazide 2 was obtained from the hydrazinolysis of carboethoxy compound 1 and exploited as a key intermediate to synthesize heterocyclic compounds with different rings.

Ex Vivo Effect of Novel Lipophosphonoxins on Root Canal Biofilm Produced by Enterococcus faecalis: Pilot Study.

(1) Background: The root canal system has complex anatomical and histological features that make it impossible to completely remove all bacteria by mechanical means only; they must be supplemented with disinfectant irrigation. Current disinfectants are unable to eliminate certain microorganisms that persist in the root canal, resulting in treatment failure. At the Institute of Organic Chemistry and Biochemistry, Prague, novel substances with the bactericidal effect, termed lipophosphonoxins (LPPOs), have been discovered. The aim of this pilot study was to investigate the ex vivo effects of second- and third-generation LPPOs on Enterococcus faecalis and compare them with 5% sodium hypochlorite (NaOCl), 0.12% chlorhexidine digluconate, and 17% ethylenediaminetetraacetic acid (EDTA). (2) Methods: The root canal’s dentin was used as a carrier for biofilm formation in the extracted human mature mandibular premolars. The samples were filled with cultivation broth and 0.25% glucose with tested solutions. In control samples, only fresh cultivation broth (negative control) and cultivation broth with bacterial suspension (growth control) were used. Each sample was inoculated with E. faecalis CCM4224 except for the negative control, and cultivation was performed. To determine the number of planktonic cells, the sample content was inoculated on blood agar. To evaluate biofilm formation inhibition, samples were placed in tubes with BHI. (3) Results: LPPOs exhibited a reduction in biofilm growth and bacteria comparable to NaOCl, and they were superior to other tested disinfectants. (4) Conclusions: The study results suggest the effect of lipophosphonoxins on E. faecalis CCM 4224 reduces planktonic bacterial cells and inhibits formation of biofilm in root canal samples.

Neurohypophyseal Peptides from Prague and Swedish Laboratories Used as Medications: Desmopressin, Terlipressin, Carbetocin. Part 1: History of Research and Beginnings of Industrial Production

From the fifties to the seventies of the last century, the neurohypophyseal peptides oxytocin and vasopressin constituted one of the main research areas at the Institute of Organic Chemistry and Biochemistry in Prague (IOCB). A significant contribution to this area is associated with the names of František Šorm, director of the said institute, and Josef Rudinger, head of the institute's peptide laboratory. At that time, newly developed research tools enabled to synthesize structural analogues of these hormones in numerous laboratories worldwide and hence to investigate the structure-activity relationships within this peptide group. Contributions of single peptide-chain positions to the respective biological activities were identified which opened a possibility to rationalize a design of peptides with a combination of changes in several positions. Several clinically interesting peptides were synthesized in the late 1960s at the IOCB and employed as therapeutics: [(Gly)3-Cys1,Lys8]-vasopressin (Glypressin Ferring®, Terli­pressin INN), 1-deamino-8-ᴅ-arginine vasopressin (Desmopressin INN, dDAVP), and later the uterotonics carbetocin (INN), widely used in obstetrics to prevent postpartum haemorrhage. Since the industrial production of peptide therapeutics was scarcely possible under the conditions of socialist economy in Czechoslovakia as well as in other countries under the Soviet influence, F. Šorm agreed to use the already established scientific contacts of IOCB with the Swedish pharmaceutical company Ferring AB and to transfer the production licences to Sweden. The license agreements were signed in 1969 and led to a quick spread of dDAVP in the substitution therapy of the central form of diabetes insipidus and, moreover, contributed to a fast upsurge of the Ferring company. Somewhat later, Glypressin was produced as a therapeutic with a prolonged action in cases of cardiovascular collapse. Contacts between Prague peptide chemists and the Ferring company lasted on a rather informal base until the end of the 1980s. After the fall of the totalitarian regime in Czechoslovakia in 1990, Ferring started a joint-venture collaboration with the newly organized Czech company Léčiva st.p. Praha in a newly established group Prague Polypeptide Institute spol. s. r.o. (later Ferring-Léčiva A.S.). A substantial part of the peptide-production capacities was then transferred to new buildings in Prague.

Reflections on the Rega Institute for Medical Research, at the fiftieth anniversary of the Rega Stichting vzw (Rega Instituut vzw, Rega Foundation).

The idea to start the Rega Foundation was conceived in 1971 at an informal meeting organized by Prof. Piet De Somer (where Prof. Alfons Billiau, Prof. André Vlerick and I were also present), before the Foundation was formally created in 1972. From the early years some antiviral compounds, such as BVDU and the aminoacyl esters of acyclovir (from which ultimately valacyclovir evolved) originated. The advent of AIDS in 1981 and the discovery of the etiologic agent (HIV) thereof in 1983 have led to the identification of an avalanche of anti-HIV compounds in which the Rega Institute has played a primordial role. Foremost among these compounds was tenofovir, discovered in collaboration with Antonín Holý from the IOCB (Institute of Organic Chemistry and Biochemistry) in Prague. Tenofovir laid the basis for the treatment of HIV (AIDS) and hepatitis B virus (HBV) infections, and in combination with emtricitabine it was the first chemical ever approved by the US FDA (Food and Drug Administration) for the prophylaxis of HIV infections.

Photochemical Properties of Propargylamine-based Polymers

Propargylamines are a promising but quite poorly studied category of organic compounds. This work aimed to study the photochemical properties of propargylamines polymers containing porphyrin fragments with electron transfer reactions. The study was carried out in 2019 at the Institute of Organic Chemistry (RAS, Moscow, Russia). The obtained polymer was irradiated with a luminous source. The absorption spectra were studied by electron paramagnetic resonance using a radio spectrometer. The presence of porphyrin and propargylamine in the polymer solution has been established to promote the reaction of complexation. This is due to the presence of double bonds in the amino groups, whereas also porphyrin and bromanil, which is an electron acceptor. The resulting data allow explaining the processes involved in photochemical reactions during the irradiation of the porphyrin complex in the presence of bromanil. In the long-wavelength part of the spectrum (above 540 nm), electron phototransfer inside the polymer molecule to the porphyrin side and between molecules from the porphyrin anion radical to the neutral polymer molecule take place.

ВУЗОВСКАЯ НАУКА В БАШКИРИИ В 1960-1980-Е ГГ.

The article deals with the development of science in higher educational institutions of Bashkiria in the 1960- 1980s, also the problem of the growth of the number of scientific and scientific-pedagogical personnel. The paper shows the dynamics of creating of research sections (departments), research industrial branch and problem laboratories, research production units in the universities of the republic. Thus, the first research laboratory in the higher educational institutions of the republic appeared in 1960, and the first research sections (departments) in 1963. The paper shows that in institutional terms, research activities were particularly intensively developed in the Ufa Oil and Aviation Institutes, the Bashkir State University. For some time, from 1963 to 1967, the former research institutes of the Bashkir branch of the USSR Academy of Sciences were part of the BSU; namely the Institute of Organic Chemistry and the Institute of Biology. However, the most rapid emergence of research laboratories in most universities of the republic dates back only to the 1980s, when they were established in the Bashkir State University, Medical and Agricultural Institutes. The article describes peculiarities of the formation of scientific trends and schools in various higher education institutions of the region. Thus, in the Bashkir Agricultural Institute, scientific research was closely related to agricultural production, in the Medical Institute - with medical and preventive practice in the republic. The Ufa Aviation and Petroleum Institutes, partly the University, served the production interests of large industrial enterprises. The article reveals that during the period under review, there occurred a certain integration of college science with academic and branch science, production, also increase the volume of contractual self accounting work took place The problem publication the results of scientific research remained acute during the study period. The issue of the implementing of the results of scientific activity in to production is touched upon. A number of difficulties in the development of science in higher educational institutions of the republic are identified in the article: the weakness of the experimental and production base, its inefficient use, the increase in the time of implementation of developments in to production, the low level of cooperation and coordination of scientific activities.

Cobalt Bis(dicarbollide) Alkylsulfonamides: Potent and Highly Selective Inhibitors of Tumor Specific Carbonic Anhydrase IX.

Invited for this month's cover is a collaboration from three institutes from the Czech Academy of Sciences: Institute of Inorganic Chemistry, Institute of Organic Chemistry and Biochemistry, and Institute of Molecular Genetics, and the University of Pardubice. The cover picture shows a family of potent and selective CA IX inhibitors that combines the structural motif of a bulky inorganic cobalt bis(dicarbollide) polyhedral ion with a propylsulfonamido anchor group. Read the full text of the article at 10.1002/cplu.202000574.

Helquats as Promoters of the Povarov Reaction: Synthesis of 1,2,3,4‐Tetrahydroquinoline Scaffolds Catalyzed by Helicene‐Viologen Hybrids

Invited for this month's cover are the synthetic and physical chemistry groups of Paul E. Reyes-Gutiérrez and Lubomír Pospíšil from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, and Charles University. The cover picture shows azoniahelicenes (helquats), which have been shown to function as organocatalysts in the Povarov reaction. Read the Full Paper at 10.1002/cplu.202000151.

Identification of Novel Carbonic Anhydrase IX Inhibitors Using High-Throughput Screening of Pooled Compound Libraries by DNA-Linked Inhibitor Antibody Assay (DIANA).

The DNA-linked inhibitor antibody assay (DIANA) has been recently validated for ultrasensitive enzyme detection and for quantitative evaluation of enzyme inhibitor potency. Here we present its adaptation for high-throughput screening of human carbonic anhydrase IX (CAIX), a promising drug and diagnostic target. We tested DIANA's performance by screening a unique compound collection of 2816 compounds consisting of lead-like small molecules synthesized at the Institute of Organic Chemistry and Biochemistry (IOCB) Prague ("IOCB library"). Additionally, to test the robustness of the assay and its potential for upscaling, we screened a pooled version of the IOCB library. The results from the pooled screening were in agreement with the initial nonpooled screen with no lost hits and no false positives, which shows DIANA's potential to screen more than 100,000 compounds per day.All DIANA screens showed a high signal-to-noise ratio with a Z' factor of >0.89. The DIANA screen identified 13 compounds with Ki values equal to or better than 10 µM. All retested hits were active also in an orthogonal enzymatic assay showing zero false positives. However, further biophysical validation of identified hits revealed that the inhibition activity of several hits was caused by a single highly potent CAIX inhibitor, being present as a minor impurity. This finding eventually led us to the identification of three novel CAIX inhibitors from the screen. We confirmed the validity of these compounds by elucidating their mode of binding into the CAIX active site by x-ray crystallography.

Corrigendum: An Experimentally Established Key Intermediate in Benzene Nitration with Mixed Acid

In this Communication the authors reported a detailed theoretical modeling on the mechanism of nitration of benzene by mixed acid. In addition, they also reported some qualitative experimental UV spectroscopic data reflecting the course of the process. Additional NMR experiments of this reaction have now revealed that under the concentrations of reactants employed no stable π-complex is formed, opposite to the assumption in the earlier study. In particular, the absorption in the UV spectrum at 320 nm (in Figure 3 of the original Communication), which was recorded almost immediately after mixing the reactants, was incorrectly assigned to an early reaction complex. The authors are indebted to Professor Svetlana Simova, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, for recording and analyzing the NMR spectra.

The chemical revolution

A play titled Elegance molekuly (The elegance of the molecule) is performed twice a month in the Czech Republic capital of Prague. Recounting the accomplishments of Antonin Holý, a chemist who discovered the compound that led to Truvada—Gilead Sciences’ breakthrough HIV/AIDS therapy—the play sells out weeks in advance. Holý, an eminent figure in the Czech science community for his work on nucleotide analog synthesis, died in 2012 at the age of 75. The Czech Republic issued a stamp in his honor. Holý’s work is important in a country that was looking for heroes during its long rebound from the repression of Soviet dominance after World War II. His achievements shine a light on the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB), where he did his research, showcasing the strength of chemistry in the country. Czech chemistry has a heritage that stretches back more than

N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences: History and Present

N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences: History and Present

Guest Editorial to Special Issue Dedicated to N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences

Guest Editorial to Special Issue Dedicated to N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences