Feature Papers in Compounds

This book represents a collection of contributions in the field of the synthesis and characterization of chemical compounds, natural products, chemical reactivity, and computational chemistry. Among its contents, the reader will find high-quality, peer-reviewed research and review articles that were published in the open access journal Compounds by members of the Editorial Board and the authors invited by the Editorial Office and Editor-in-Chief

Diffusion of tin from TEC-8 conductive glass into mesoporous titanium dioxide in dye sensitized solar cells

The photoanode of a dye sensitized solar cell is typically a mesoporous titanium dioxide thin film adhered to a conductive glass plate. In the case of TEC-8 glass, an approximately 500 nm film of tin oxide provides the conductivity of this substrate. During the calcining step of photoanode fabrication, tin diffuses into the titanium dioxide layer. Scanning Electron Microscopy and Electron Dispersion Microscopy are used to analyze quantitatively the diffusion of tin through the photoanode. At temperatures (400 to 600 °C) and times (30 to 90 min) typically employed in the calcinations of titanium dioxide layers for dye sensitized solar cells, tin is observed to diffuse through several micrometers of the photoanode. The transport of tin is reasonably described using Fick\u27s Law of Diffusion through a semi-infinite medium with a fixed tin concentration at the interface. Numerical modeling allows for extraction of mass transport parameters that will be important in assessing the degree to which tin diffusion influences the performance of dye sensitized solar cells

Mechanisms of the Intriguing Rearrangements of Activated Organic Species

The β-acyloxyalkyl radical rearrangement has been known since 1967 but its mechanism is still not fully understood, despite considerable investigation. Since the migration of a β-trifluoroacetoxy group generally proceeds more rapidly and with more varied regiochemistry than its less electronegative counterparts, this reaction was studied in the hope of understanding more about the subtleties of the mechanism of the β- acyloxyalkyl radical rearrangement. The mechanism of the catalysed rearrangement of Nalkoxy- 2(1H)-pyridinethiones was also explored because preliminary studies indicated that the transition state (TS) for this process was isoelectronic with TSs postulated for the β-acyloxyalkyl radical and other novel rearrangements. ¶ ..

The role of L-ascorbic acid in S-nitrosothiol decomposition and aspects of the nitrosation of thiones

Ascorbic acid has been found to promote nitrosothiol decomposition via two pathways. In the first, ascorbic acid acts as a reducing agent for added or adventitious copper (II), producing copper (I). This reacts with the nitrosothiol, giving nitric oxide and disulfide as the ultimate products. The reaction requires only small quantities of ascorbic acid, and is catalytic in copper. The second pathway requires higher concentrations of ascorbic acid, the stoichiometry being one mole of ascorbic acid to two moles of nitrosothiol. The products are nitric oxide and thiol, and the reaction has been interpreted in terms of rate limiting nucleophihc attack by ascorbate at the nitroso nitrogen, followed by decomposition of the 0-nitroso ascorbate formed to nitric oxide and dehydroascorbic acid. The rate equation is first order in both the nitrosothiol and ascorbic acid, and the entropy of activation is significantly negative. pH - rate profiles reveal the ascorbate dianion is much more reactive than the monoanion, and that the neutral form has negligible reactivity. Nitrosation of thione-containing nitrogen heterocycles by nitrous acid leads to the equilibrium formation of =SNO(^+) species; large equilibrium constants are observed. The reactions exhibit many of the features generally observed in nitrosation, including catalysis by halides and thiocyanate, and some participation by dinitrogen trioxide as a nitrosating agent. The nitrosation rate constants are large, approaching values representing the encounter-controlled limit. The =SNO(^+) species are generally unstable, decomposing under acidic conditions to nitric oxide and a disulfide. Decomposition of S-nitrosated 4-thiopyridine showed hydrolysis occurs at pH 7.4, re-forming the thione. The nitroso species reacts rapidly with ascorbate, forming nitric oxide and thione

Benzoyl isothiocyanates derived ligands as potential HIV-1 protease inhibitors and their reactions with gold ions

The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease

MECHANISTIC INVESTIGATIONS AND THE DEVELOPMENT OF NEW TRANSFORMATIONS IN ACRIDINIUM-MEDIATED PHOTOREDOX CATALYSIS

Photoredox catalysis has rapidly expanded to become an indispensible tool for synthetic chemists. Recent developments in this field have demonstrated the potential for photoredox systems to activate normally unreactive substrates and leverage reactivity that cannot be accessed in classical two-electron pathways. Organic chromophores offer particular advantages over their transition metal counterparts, and an introduction to the principles of photoredox catalysis and the properties of common organic photoredox catalysts is provided. Given the importance of solution phase redox potentials in selecting successful catalyst/substrate combinations, we have utilized computational methods to predict redox potentials for a large set of representative organic compounds, demonstrating the predictive power of the computational approach by comparing the calculated redox potential values with experimentally measured potentials. The Nicewicz laboratory has made use of acridinium-based photoredox catalysts to accomplish the anti-Markovnikov addition of a number of nucleophiles to alkenes, and these systems were thought to rely on the cooperative activity of the acridinium catalyst and a redox active hydrogen atom donor. An in-depth investigation of the proposed mechanism illuminated key photophysical properties of the acridinium catalyst and confirmed the feasibility of a crucial mechanistic step that unites the activity of the co-catalysts. Observations in the course of this inquiry prompted us to design more robust acridinium catalysts, one of which was employed the development of a photoredox catalytic aryl C-H amination reaction. This methodology features the use of a nitroxyl radical co-catalyst and oxygen to achieve the net oxidative transformation, which furnishes aryl amines with high site-selectivity. An array of arene/amine combinations were shown to undergo the aryl amination reaction, demonstrating the value of this protocol in generating diverse libraries of functionalized arenes. Kinetic analysis of the reaction manifold revealed that product inhibition is a significant mechanistic factor. This observation could inform strategies to improve the efficiency of the reaction and expand the substrate scope beyond current limitations.Doctor of Philosoph

Rational development of stabilized cyclic disulfide redox probes and bioreductive prodrugs to target dithiol oxidoreductases

Countless biological processes allow cells to develop, survive, and proliferate. Among these, tightly balanced regulatory enzymatic pathways that can respond rapidly to external impacts maintain dynamic physiological homeostasis. More specifically, redox homeostasis broadly affects cellular metabolism and proliferation, with major contributions by thiol/disulfide oxidoreductase systems, in particular, the Thioredoxin Reductase Thioredoxin (TrxR/Trx) and the Glutathione Reductase-Glutathione-Glutaredoxin (GR/GSH/Grx) systems. These cascades drive vital cellular functions in many ways through signaling, regulating other proteins' activity by redox switches, and by stoichiometric reductant transfers in metabolism and antioxidant systems. Increasing evidence argues that there is a persistent alteration of the redox environment in certain pathological states, such as cancer, that heavily involve the Trx system: upregulation and/or overactivity of the Trx system may support or drive cancer progression, making both TrxR and Trx promising targets for anti-cancer drug development. Understanding the biochemical mechanisms and connections between certain redox cascades requires research tools that interact with them. The state-of-the-art genetic tools are mostly ratiometric reporters that measure reduced:oxidized ratios of selected redox pairs or the general thiol pool. However, the precise cellular roles of the central oxidoreductase systems, including TrxR and Trx, remain inaccessible due to the lack of probes to selectively measure turnover by either of these proteins. However, such probes would allow measuring their effective reductive activity apart from expression levels in native systems, including in cells, animals, or patient samples. They are also of high interest to identify chemical inhibitors for TrxR/Trx in cells and to validate their potential use as anti-cancer agents (to date, there is no selective cellular Trx inhibitor, and most known TrxR inhibitors were not comprehensively evaluated considering selectivity and potential off-targets). However, small molecule redox imaging tools are underdeveloped: their protein specificity, spectral properties, and applicability remain poorly precedented. This work aimed to address this opportunity gap and develop novel, small molecule diagnostic and therapeutic tools to selectively target the Trx system based on a modular trigger cargo design: artificial cyclic disulfide substrates (trigger) for oxidoreductases are tethered to molecular agents (cargo) such that the cargo’s activity is masked and is re-established only through reduction by a target protein. The rational design of these novel reduction sensors to target the cell's strongest disulfide-reducing enzymes was driven by the following principles: (i) cyclic disulfide triggers with stabilized ring systems were used to gain low reduction potentials that should resist reduction except by the strongest cellular reductases, such as Trx; and (ii) the cyclic topology also offers the potential for kinetic reversibility that should select for dithiol-type redox proteins over the cellular monothiol background. Creating imaging agents based on such two-component designs to selectively measure redox protein activity in native cells required to combine the correct trigger reducibility, probe activation kinetics, and imaging modalities and to consider the overall molecular architecture. The major prior art in this field has applied cyclic 5-membered disulfides (1,2 dithiolanes) as substrates for TrxR in a similar way to create such tools. However, this motif was described elsewhere as thermodynamically instable and was due to widely used for dynamic covalent cascade reactions. By comparing a novel 1,2 dithiolane-based probe to the state-of-the-art probes, including commercial TrxR sensors, by screening a conclusive assay panel of cellular TrxR modulations, I clarified that 1,2 dithiolanes are not selective substrates for TrxR in biological settings (Nat Commun 2022). Instead, aiming for more stable ring systems and thus more robust redox probes, during this work, I developed bicyclic 6 membered disulfides (piperidine fused 1,2 dithianes) with remarkably low reduction potentials. I showed that molecular probes using them as reduction sensors can be mostly processed by thioredoxins while being stable against reduction by GSH. The thermodynamically stabilized decalin like topology of the cis-annelated 1,2 dithianes requires particularly strong reductants to be cleaved. They also select for dithiol type redox proteins, like Trx, based on kinetic reversibility and offer fast cyclization due to the preorganization by annelation (JACS 2021). This work further expanded the system’s modularity with structural cores based on piperazine-fused 1,2 dithianes with the two amines allowing independent derivatization. Diagnostic tools using them as reduction sensors proved equally robust but with highly improved activation kinetics and were thus cellularly activated. Cellular studies evolved that they are substrates for both Trxs and their protein cousins Grxs, so measuring the cellular dithiol protein pool rather than solely Trx activity (preprint 2023). Finally, a trigger based on a slightly adapted reduction sensor, a desymmetrized 1,2 thiaselenane, was designed for selective reduction by TrxR’s selenol/thiol active site, then combined with a precipitating large Stokes’ shift fluorophore and a solubilizing group, to evolve the first selective probe RX1 to measure cellular TrxR activity, which even allowed high throughput inhibitor screening (Chem 2022). The central principle of this work was further advanced to therapeutic prodrugs based on the duocarmycin cargo (CBI) with tunable potency (JACS Au 2022) that can be used to create off-to-on therapeutic prodrugs. Such CBI prodrugs employing stabilized 1,2 dichalcogenide triggers proved to be cytotoxins that depend on Trx system activity in cells. They could further be exploited for cell-line dependent reductase activity profiling by screening their redox activation indices, the reduction-dependent part of total prodrug activation, in 177 cell lines. Beyond that, these prodrugs were well-tolerated in animals and showed anti-cancer efficacy in vivo in two distinct mouse tumor models (preprint 2022). Taken together, I introduced unique monothiol-resistant reducible motifs to target the cellular Trx system with chemocompatible units for each for TrxR and Trx/Grx, where the cyclic nature of the dichalcogenides avoids activation by GSH. By using them with distinct molecular cargos, I developed novel selective fluorescent reporter probes; and introduced a new class of bioreductive therapeutic constructs based on a common modular design. These were either applied to selectively measure cellular reductase activity or to deliver cytotoxic anti cancer agents in vivo. Ongoing work aims to differentiate between the two major redox effector proteins Trx and Grx, requiring additional layers of selectivity that may be addressed by tuned molecular recognition. The flexible use of various molecular cargos allows harnessing the same cellular redox machinery by either probes or prodrugs. This allows predictive conclusions from diagnostics to be directly translated into therapy and offers great potential for future adaptation to other enzyme classes and therapeutic venues.Die zelluläre Redox-Homöostase hängt von Thiol/Disulfid-Oxidoreduktasen ab, die den Stoffwechsel, die Proliferation und die antioxidative Antwort von Zellen beeinflussen. Die wichtigsten Netzwerke sind die Thioredoxin Reduktase-Thioredoxin (TrxR/Trx) und Glutathion Reduktase-Glutathion-Glutaredoxin (GR/GSH/Grx) Systeme, die über Redox-Schalter in Substratproteinen lebenswichtige zelluläre Funktionen steuern und so an der Redox-Regulation und -Signalübertragung beteiligt sind. Persistente Veränderungen des Redoxmilieus in pathologischen Zuständen, wie z. B. bei Krebs, sind in hohem Maße mit dem Trx-System verbunden. Eine Hochregulierung und/oder Überaktivität des Trx-Systems, die bei vielen Krebsarten auftreten, unterstützt zudem das Fortschreiten des Krebswachstums, was TrxR/Trx zu vielversprechenden Zielproteinen für die Entwicklung neuer Krebsmedikamente macht. Um die biochemischen Prozesse dahinter zu erforschen, sind spezielle Techniken zur Visualisierung und Messung enzymatischer Aktivität nötig. Die hierzu geeigneten, meist genetischen Sensoren messen ratiometrisch das Verhältnis reduzierter/oxidierter Spezies in zellulärem Umfeld oder spezifisch ausgewählte Redoxpaare. Die weitere Erforschung der exakten Funktion von TrxR/Trx und deren Substrate ist jedoch durch mangelnde Nachweismethoden limitiert. Diese sind außerdem zur Validierung chemischer Hemmstoffe für TrxR/Trx in Zellen und deren potenziellen Verwendung als Krebsmittel von großem Interesse. Bislang gibt es keinen selektiven zellulären Trx-Inhibitor und potenzielle Off-Target-Effekte der bekannten TrxR-Inhibitoren wurden nicht abschließend bewertet. Ziel dieser Arbeit ist die Entwicklung niedermolekularer, diagnostischer und therapeutischer Werkzeuge, die selektiv auf das Trx-System abzielen und auf einem modularen Trigger-Cargo Design basieren. Hierzu werden zyklische Disulfid-Substrate (Trigger) für Oxidoreduktasen so mit molekularen Wirkstoffen (Cargo) verknüpft, dass dabei die Wirkstoffaktivität maskiert, und erst nach Reduktion durch ein Zielprotein wiederhergestellt wird. Diese neuartigen, synthetischen Reduktionssensoren basieren auf den folgenden Grundprinzipien: (i) Zyklische Disulfide sind thermodynamisch stabilisiert und können nur durch die stärksten Reduktasen gespalten werden; und (ii) die zyklische Topologie ermöglicht die kinetische Reversibilität der zwei Thiol-Disulfid-Austauschreaktionen, die eine erste Reaktion mit Monothiolen, wie z. B. GSH, sofort umkehrt und so eine vollständige Reduktion verhindert. Die meisten früheren Arbeiten auf diesem Gebiet verwendeten ein zyklisches, fünfgliedriges Disulfid (1,2 Dithiolan) als Substrat für TrxR. Das gleiche Strukturmotiv wurde jedoch an anderer Stelle als thermodynamisch instabil beschrieben und aufgrund dieser Eigenschaft explizit für dynamische Kaskadenreaktionen verwendet. Deshalb vergleicht diese Arbeit zu Beginn einen neuen 1,2 Dithiolan basierten fluorogenen Indikator mit bestehenden, z. T. kommerziellen, Redox Sonden für TrxR in einer Reihe von Zellkultur-Experimenten unter Modulation der zellulären TrxR Aktivität und stellt so einen Widerspruch in der Literatur klar: 1,2 Dithiolane eignen sich nicht als selektive Substrate für TrxR, da sie labil sowohl gegen die Reduktion durch andere Redoxproteine, als auch gegen den Monothiol Hintergrund in Zellen sind (Nat. Commun. 2022). Als alternatives Strukturmotiv wird in dieser Arbeit ein bizyklisches sechsgliedriges Disulfid (anneliertes 1,2 Dithian) etabliert. Durch sein niedriges Reduktionspotenzial, also seine hohe Resistenz gegen Reduktion, werden molekulare Sonden basierend auf diesem 1,2 Dithian als Reduktionssensor fast ausschließlich von Trx aktiviert, nicht aber von TrxR oder GSH (JACS 2021). Dieses Kernmotiv bestimmt dabei die Reduzierbarkeit, und damit die Enzymspezifität, durch seine zyklische Natur und die Annelierung, auch unter Verwendung unterschiedlicher Farb-/Wirkstoffe. Auf dieser Grundlage konnte die molekulare Struktur durch einen weiteren Modifikationspunkt für die flexible Verwendung weiterer funktioneller Einheiten ergänzt werden. Obwohl zelluläre Studien ergaben, dass diese neuartigen 1,2 Dithian Einheiten in Zellen sowohl Trx als auch das strukturell verwandte Grx adressieren, sind die daraus resultierenden diagnostischen Moleküle wertvoll, um den katalytischen Umsatz zellulärer Dithiol-Reduktasen, der sogenannten Trx Superfamilie, selektiv anzuzeigen (Preprint 2023). Begünstigt durch das modulare Moleküldesign stellt diese Arbeit zudem das erste Reportersystem RX1 zum selektiven Nachweis der TrxR-Aktivität in Zellen vor. Es basiert auf der Verwendung eines zyklischen, unsymmetrischen Selenenylsulfid-Sensors (1,2 Thiaselenan), der selektiv von dem einzigartigen Selenolat der TrxR angegriffen wird, und dadurch letztlich nur von TrxR reduziert werden kann. RX1 eignete sich zudem für eine Hochdurchsatz-Validierung bestehender TrxR Inhibitoren und unterstreicht dadurch den kommerziellen Nutzen derartiger Diagnostika (Chem 2022). Das zentrale Trigger-Cargo Konzept dieser Arbeit wurde für therapeutische Zwecke weiterentwickelt und nutzt dabei den einzigartigen Wirkmechanismus der Duocarmycin-Naturstoffklasse (CBI) (JACS Au 2022) zur Entwicklung reduktiv aktivierbarer Therapeutika. CBI Prodrugs basierend auf stabilisierten Redox-Schaltern (1,2 Dithiane für Trx; 1,2 Thiaselenan für TrxR) reagierten signifikant auf TrxR-Modulation in Zellen. Sie wurden darüber hinaus durch das Referenzieren ihrer Aktivität gegenüber nicht-reduzierbaren Kontrollmoleküle für die Erstellung zelllinienabhängiger Profile der Reduktaseaktivität in 177 Zelllinien genutzt. Schließlich waren diese neuen Krebsmittel im Tiermodell gut verträglich und zeigten in zwei verschiedenen Mausmodellen eine krebshemmende Wirkung (Preprint 2022b). Zusammenfassend präsentiert diese Dissertation monothiol-resistente reduzierbare Trigger-Einheiten für das zelluläre Trx-System zur Entwicklung neuartiger, selektiver Reporter-Sonden, sowie eine neue Klasse reduktiv aktivierbarer Krebsmittel auf Basis eines adaptierbaren Trigger-Cargo Designs. Diese fanden entweder zur selektiven Messung zellulärer Proteinaktivität oder zum Einsatz als Antikrebsmittel Verwendung. Es wurden chemokompatible Motive sowohl für TrxR als auch für Trx/Grx identifiziert, wobei deren zyklische Natur eine Aktivierung durch GSH verhindert. Eine weitere Differenzierung zwischen den beiden Redox-Proteinen Trx und Grx und anderen Proteinen der Trx-Superfamilie erfordert eine zusätzliche Ebene der Selektierung, z. B. durch molekulare Erkennung, und ist Gegenstand laufender Arbeiten. Die flexible Verwendung verschiedener molekularer Wirkstoffe ermöglicht dabei die „Pipeline-Entwicklung“ von Diagnostika und Therapeutika, die von der zellulären Redox-Maschinerie analog umgesetzt werden, und dadurch Schlussfolgerungen aus der Diagnostik direkt auf eine Therapie übertragbar machen. Dies birgt großes Potenzial für künftige Entwicklungen bei einer potenziellen Übertragung des modularen Konzepts auf andere Enzymklassen und therapeutische Einsatzgebiete

Тезисы докладов

В сборнике представлены тезисы докладов XXVI Международной Чугаевской конференции по координационной химии, VII Международного симпозиума “Дизайн и синтез супрамолекулярных архитектур” и III Молодёжной конференции-школы “Физико-химические методы в химии координационных соединений”, проходивших в Казани с 6 по 10 октября 2014 года.75