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Structural stury of carboranes by mass spectrometry
Navrátilová, Romana ; Vávrová, Milada (referee) ; Čáslavský, Josef (advisor)
Boron cluster compounds are substances clearly synthetic, which don't exist outdoors. This group covers boranes, heteroboranes and their derivatives. They are synthesized and examined mostly for their extraordinary structural and bonding properties. Their study also brought many remarkable findings and even allowed practical use of these compounds in science and technology. This thesis is focused on the application of mass spectrometry for the identification of boranes and heteroboranes and on the study of their fragmentation mechanisms using tandem mass spectrometry on spherical ion trap.
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Self-assembly of boron cluster compounds and their coassembly with polymers
Ďorďovič, Vladimír ; Matějíček, Pavel (advisor) ; Adamczyk-Wozniak, Agnieszka (referee) ; Nunez Aguilera, Maria Rosario (referee)
This thesis focuses on the self-assembly of the boron cluster compounds and the coassembly of metallacaborane cobalt bis(dicarbollide), COSAN, with hydrophilic polymers. The research was motivated by the discovery of HIV inhibition by COSAN and its conjugates. Therefore, we decided to study in detail the behavior of boron cluster compounds in water. We demonstrated the amphiphilic character of several boranes and carboranes by the study of surface tension and self-assembly despite the absence of classical amphiphilic topology. The behavior of COSAN showed similarities with classical surfactants, such as SDS, whereas the behavior of smaller clusters with high charge density reminded of hydrotropes or chaotropes. Furthermore, we searched for the most suitable carriers of COSAN for drug delivery. Based on the earlier findings that COSAN interacts with both poly(ethylene oxide), PEO, and poly(2-oxazoline), POX, we prepared nanoparticles by mixing COSAN with block copolymers of various types of POX. Comparing linear and star-like block copolymers, we showed that the polymer architecture has a crucial role in the morphology of nanoparticles. In addition, we proved different selectivity of alkaline cations towards PEO and POX, resulting in the different structures of nanoparticles depending on the present...
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Synthesis of new carborane and metallacarborane bulding blocks appliable in design of biologically active compounds
Nekvinda, Jan ; Grüner, Bohumír (advisor) ; Janoušek, Zbyněk (referee)
Compounds with carboxylic and amidic functions belong to basic structural blocks, which are used for construction of functional molecules in organic, organometallic and also in carborane chemistry. However, considering cobalt bis(dicarbollide)(1-) ion, the synthetic ways to these derivatives have been virtually unknown. A published procedure on lithiation in THF and reaction with CO2 leading to mono- and dicarboxylic acids had failed in our hands. Nevertheless, a detailed revision of the experimental conditions provided finally good yields of mixture of both acids, which could be separated by chromatography and crystallization, and compound of general formulation [(1-HOOC-1,2-C2B9H10)(1',2'-C2B9H10)-3,3'-Co(III)]- and stereoisomeric mixture of [(HOOC)2-(1,2-C2B9H10)2-3,3'-Co(III)]- were characterized for the first time by combination of NMR, MS and HPLC. Also, the carboxylic acid derivatives with methylene and ethylene connectors of the general formula [(1-HOOC-(CH2)n-1,2- C2B9H10)(1',2'-C2B9H10)-3,3'-Co(III)]- were prepared by lithiation of Cs1 in DME at low temperatures followed by reaction with BrCH2COOEt and subsequent hydrolysis of the resulting ester or by oxidation of the respective propylhydroxy derivative. The acids were converted to reactive p-nitrophenyl esters...
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Carborane structural blocks in medicinal chemistry
Nekvinda, Jan ; Grüner, Bohumír (advisor) ; Machara, Aleš (referee) ; Janoušek, Zbyněk (referee)
This work deals with carborane and metallacarborane clusters, in terms of their fundamental chemistry and complexation with cyclodextrins, and in the context of emerging pharmacophores applicable in medicinal chemistry. Arguably, the most important part of this work is the preparation of cobalt bis(dicarbollide) sulfamide derivatives. The sulfamido group is attached to the metallacarborane carbon vertex by an alkyl chain that may be modified in its length. This was accomplished by, firstly, the abstraction of the acidic hydrogen, located on the {CH}-vertex from the metallacarborane, by reaction with lithium base, followed by, secondly, reaction with electrophilic agents (PFA, oxirane and oxetane), which leads to a cascade of reactions to give the desired sulfamide derivatives. These compounds were then tested by collaborators in other institutes for in vitro and in vivo activity towards Carbonic Anhydrase IX (CA IX), which is an enzyme associated with tumour growth. In vivo tests on mice have shown that these types of substances are able to effectively reduce tumour size by 30%. The synthetic research continued with the preparation of sulfonamide compounds of the isomers of the carborane series. The reactions began exclusively with propylhydroxy carborane starting materials, which provide optimum...
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Carborane structural blocks in medicinal chemistry
Nekvinda, Jan
This work deals with carborane and metallacarborane clusters, in terms of their fundamental chemistry and complexation with cyclodextrins, and in the context of emerging pharmacophores applicable in medicinal chemistry. Arguably, the most important part of this work is the preparation of cobalt bis(dicarbollide) sulfamide derivatives. The sulfamido group is attached to the metallacarborane carbon vertex by an alkyl chain that may be modified in its length. This was accomplished by, firstly, the abstraction of the acidic hydrogen, located on the {CH}-vertex from the metallacarborane, by reaction with lithium base, followed by, secondly, reaction with electrophilic agents (PFA, oxirane and oxetane), which leads to a cascade of reactions to give the desired sulfamide derivatives. These compounds were then tested by collaborators in other institutes for in vitro and in vivo activity towards Carbonic Anhydrase IX (CA IX), which is an enzyme associated with tumour growth. In vivo tests on mice have shown that these types of substances are able to effectively reduce tumour size by 30%. The synthetic research continued with the preparation of sulfonamide compounds of the isomers of the carborane series. The reactions began exclusively with propylhydroxy carborane starting materials, which provide optimum...
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Carborane structural blocks in medicinal chemistry
Nekvinda, Jan
This work deals with carborane and metallacarborane clusters, in terms of their fundamental chemistry and complexation with cyclodextrins, and in the context of emerging pharmacophores applicable in medicinal chemistry. Arguably, the most important part of this work is the preparation of cobalt bis(dicarbollide) sulfamide derivatives. The sulfamido group is attached to the metallacarborane carbon vertex by an alkyl chain that may be modified in its length. This was accomplished by, firstly, the abstraction of the acidic hydrogen, located on the {CH}-vertex from the metallacarborane, by reaction with lithium base, followed by, secondly, reaction with electrophilic agents (PFA, oxirane and oxetane), which leads to a cascade of reactions to give the desired sulfamide derivatives. These compounds were then tested by collaborators in other institutes for in vitro and in vivo activity towards Carbonic Anhydrase IX (CA IX), which is an enzyme associated with tumour growth. In vivo tests on mice have shown that these types of substances are able to effectively reduce tumour size by 30%. The synthetic research continued with the preparation of sulfonamide compounds of the isomers of the carborane series. The reactions began exclusively with propylhydroxy carborane starting materials, which provide optimum...
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Electrochemical Investigation of Different Boron Cluster Compounds in Water-based Electrolytes
Fojt, Lukáš ; Vespalec, Radim ; Fojta, Miroslav ; Grüner, Bohumír
Boron cluster compounds (BCC) belongs to one or the proud sing compounds which ace used for medical treatment Their use for biochemical purposes is connected with use of water-based environments. Up to now, the BCC were predominantly characterized in non-aqueous milieus Therefore, we decided to undertake electrochemical research of BCC in water-based electrolytes. We have investigated several boron clusters with structures containing different number of vertexes (from 3 to 18), The structures were modified by endo- and exo- skeletal substituents. All used BCC were electrochemically active in broad potential region. which implies their possible use as biomarkers with tunable electrochemical response.
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Carborane structural blocks in medicinal chemistry
Nekvinda, Jan ; Grüner, Bohumír (advisor) ; Machara, Aleš (referee) ; Janoušek, Zbyněk (referee)
This work deals with carborane and metallacarborane clusters, in terms of their fundamental chemistry and complexation with cyclodextrins, and in the context of emerging pharmacophores applicable in medicinal chemistry. Arguably, the most important part of this work is the preparation of cobalt bis(dicarbollide) sulfamide derivatives. The sulfamido group is attached to the metallacarborane carbon vertex by an alkyl chain that may be modified in its length. This was accomplished by, firstly, the abstraction of the acidic hydrogen, located on the {CH}-vertex from the metallacarborane, by reaction with lithium base, followed by, secondly, reaction with electrophilic agents (PFA, oxirane and oxetane), which leads to a cascade of reactions to give the desired sulfamide derivatives. These compounds were then tested by collaborators in other institutes for in vitro and in vivo activity towards Carbonic Anhydrase IX (CA IX), which is an enzyme associated with tumour growth. In vivo tests on mice have shown that these types of substances are able to effectively reduce tumour size by 30%. The synthetic research continued with the preparation of sulfonamide compounds of the isomers of the carborane series. The reactions began exclusively with propylhydroxy carborane starting materials, which provide optimum...
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Self-assembly of boron cluster compounds and their coassembly with polymers
Ďorďovič, Vladimír ; Matějíček, Pavel (advisor) ; Adamczyk-Wozniak, Agnieszka (referee) ; Nunez Aguilera, Maria Rosario (referee)
This thesis focuses on the self-assembly of the boron cluster compounds and the coassembly of metallacaborane cobalt bis(dicarbollide), COSAN, with hydrophilic polymers. The research was motivated by the discovery of HIV inhibition by COSAN and its conjugates. Therefore, we decided to study in detail the behavior of boron cluster compounds in water. We demonstrated the amphiphilic character of several boranes and carboranes by the study of surface tension and self-assembly despite the absence of classical amphiphilic topology. The behavior of COSAN showed similarities with classical surfactants, such as SDS, whereas the behavior of smaller clusters with high charge density reminded of hydrotropes or chaotropes. Furthermore, we searched for the most suitable carriers of COSAN for drug delivery. Based on the earlier findings that COSAN interacts with both poly(ethylene oxide), PEO, and poly(2-oxazoline), POX, we prepared nanoparticles by mixing COSAN with block copolymers of various types of POX. Comparing linear and star-like block copolymers, we showed that the polymer architecture has a crucial role in the morphology of nanoparticles. In addition, we proved different selectivity of alkaline cations towards PEO and POX, resulting in the different structures of nanoparticles depending on the present...
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Synthesis of new carborane and metallacarborane bulding blocks appliable in design of biologically active compounds
Nekvinda, Jan ; Grüner, Bohumír (advisor) ; Janoušek, Zbyněk (referee)
Compounds with carboxylic and amidic functions belong to basic structural blocks, which are used for construction of functional molecules in organic, organometallic and also in carborane chemistry. However, considering cobalt bis(dicarbollide)(1-) ion, the synthetic ways to these derivatives have been virtually unknown. A published procedure on lithiation in THF and reaction with CO2 leading to mono- and dicarboxylic acids had failed in our hands. Nevertheless, a detailed revision of the experimental conditions provided finally good yields of mixture of both acids, which could be separated by chromatography and crystallization, and compound of general formulation [(1-HOOC-1,2-C2B9H10)(1',2'-C2B9H10)-3,3'-Co(III)]- and stereoisomeric mixture of [(HOOC)2-(1,2-C2B9H10)2-3,3'-Co(III)]- were characterized for the first time by combination of NMR, MS and HPLC. Also, the carboxylic acid derivatives with methylene and ethylene connectors of the general formula [(1-HOOC-(CH2)n-1,2- C2B9H10)(1',2'-C2B9H10)-3,3'-Co(III)]- were prepared by lithiation of Cs1 in DME at low temperatures followed by reaction with BrCH2COOEt and subsequent hydrolysis of the resulting ester or by oxidation of the respective propylhydroxy derivative. The acids were converted to reactive p-nitrophenyl esters...
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