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Aminophosphinic acids
Kruliš, Tomáš ; Kubíček, Vojtěch (advisor) ; Gyepes, Róbert (referee)
Two phosphinic acids were prepared: 1-hydroxy-ethan-1,1-bis[N,N- bis(karboxymethyl)aminomethyl]phosphinic acid; H6L1 and methylenebis[N,N- bis(karboxymethyl)aminomethyl]phosphinic acid; H6L2 . Acid-base and complexation properties were studied by potenciometric titrations. Complexes of both ligands with Cu2+ ions were studied in detail using UV/VIS spectrometry. Keywords: Organophosphorus synthesis, bisphosphinic acids, coordination properties
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Physico-Chemical Properties of Drugs
Tomanová, Pavla ; Kubíček, Vladimír (advisor) ; Nováková, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of biophysics and physical chemistry Author: Pavla Tomanová Supervisor: Ing. Vladimír Kubíček, CSc. Thesis title: Physico-Chemical properties of drugs This thesis deals with measuring dissociation constants (the pKa value) and the lipophilicity of nitrogenous heterocycle derivatives produced at the Faculty of Pharmacy in Hradec Králové. Two methods were used to determine the pK value: potentiometric titration and spectrophotometry. Potentiometric titration almost invariably produced relatively exact results, however the results of pK value obtained by spectrophotometry were sometimes difficult to replicate. Dissociation constants were compared on the basis of the method applied, and also with the theoretically determined dissociation constant calculated by means of the ChemDraw Ultra 12.0 software. The results obtained by the two experimental methods turned out to be very similar, corresponding to the theoretical pK value. Lipophilicity is another essential property of drugs tested in the preclinical stage. It specifies the aqueous or lipophilic phase affinity of a drug, substantially affecting the drug's ADMET in organism. Lipophilicity was determined on the basis of capacity factor value identified by RP-HPLC measurement using...
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Lanthanide macrocyclic complexes with phosphonate/phosphinate pendant arms
Procházková, Soňa ; Kubíček, Vojtěch (advisor) ; Cígler, Petr (referee) ; Řezanka, Pavel (referee)
Imaging methods have become an integral part of diagnostic and therapeutic procedures in current medicine. Contrast agents based on metal complexes are often used to improve the final image. Complexes contain radioisotopes in nuclear medicine and gadolinium(III) ion in MRI. These complexes have to show high kinetic and thermodynamic stability and their preparation must not be time consuming. H4DOTA and its derivatives are convenient type of ligand for the formation of stable complexes. This work has focused on phosphonate and phosphinate derivatives of the ligand H4DOTA. The studied compounds can be divided into ligands containing only methylphosphinate/phosphonate (H4DO3APH, H5DO3APOH) and ligands with a second coordination center (H6DO3APIDA, H5DO3APPIN, H4DO3APAM, H8DO3APBP a H7DOTAMBP). The work has examined the possibilities of influencing the way and rate of complexation under different conditions. In order to approach the preparation conditions of radio complexes, kinetics measurements were performed not only under the metal ions excess, but also under the ligand excess. The aim was to compare the results of both types of measurements, which often showed to be different. A mechanism for the formation of various types of intermediates formed during complexation has been proposed. The...
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Complexes of macrocyclic ligands with phosphonate and phosphinate penant arms for molecular imaging
Pazderová, Lucia ; Kubíček, Vojtěch (advisor) ; Pinkas, Jiří (referee) ; Polášek, Miloslav (referee)
In an effort to increase the thermodynamic stability and the kinetic inertness of the complexes, the five new azamacrobicyclic ligands derived from TACN, cyclen, and cyclam have been prepared. The ligands were decorated with phosphinate or phosphonate pendant arms to maintain fast complexation. Since the ascending importance of targeted diagnostic and therapy, the bone-targeted non-bridged cyclam derivative with phosphinate-bis(phosphonate) pendant arm (H5TE1PBP) has also been synthesized. The ligands were studied with respect to their application. The bridged TACN (H2bpbtacn) and cyclen (H4bpbcen) ligands show high macrocyclic basicity (logK1 = 12.25 and 12.70, respectively). The thermodynamic stability of H2bpbtacn with Cu(II) ion is more than ten orders of magnitude lower than that of the NOTA ligand. The stability constants of H4bpbcen with Cu(II) and Zn(II) ions are comparable to those given for the DOTA. The stability of Ln(III)-bpbcen complexes is 7-10 orders of magnitude lower compared to DOTA complexes. For both ligands, the lower thermodynamic stability of the complexes is attributed to the high rigidity of the ligand structure. The bridged cyclam derivatives with phosphonate (H4TE2P), bis(phosphinate) (H4TE2bpin), or phosphinate (H2TE2PH) pendants are characterized by high stability of...
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Phosphonate and phosphinate derivatives of dipicolylamine
Hlinová, Veronika
The Diploma Thesis deals with preparation of one phoshonate and two phospinate derivatives of dipicolylamine. Dissociation constants of prepared ligands were determined by potentiometric and NMR titration. Coordination properties of the compounds were studied by combination of potentiometry and UV-VIS spectrophotometry. Stability constants of complexes with selected transition metal ions (Cu2+ , Ni2+ a Zn2+ ) and alkali-earth metals ions (Ca2+ , Mg2+ ) were calculated. Acid-base and coordination properties in the solid state were studied by X-ray diffraction on single-crystals.
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Complexes of polydentate ligands
Sedláčková, Simona ; Kubíček, Vojtěch (advisor) ; Kotek, Jan (referee)
Polydentate ligands are useful in many industries, mainly because of their ability to form complexes. The aim of this thesis is to study acid-base and coordination properties of polydentate ligands from the group of polyaminopolyphosphonates DTPMP and HMDTMP. The protonation constants of ligands as well as stability constants of complexes with biologically relevant ions Cu2+ , Zn2+ , Ni2+ , Mg2+ , Ca2+ , Co2+ , K+ and Na+ were determined by potentiometric titration. 31 P-NMR titration was used to determine pKa on nitrogen atoms, which could not be measured by potenciometric titration. Seven pKa for HMDTMP ligand and nine for DTPMP were obtained. The stability constants show that the HMDTMP ligand forms less stable complexes than the DTPMP ligand.
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Phosphonate and phosphinate derivatives of dipicolylamine
Hlinová, Veronika
The Diploma Thesis deals with preparation of one phoshonate and two phospinate derivatives of dipicolylamine. Dissociation constants of prepared ligands were determined by potentiometric and NMR titration. Coordination properties of the compounds were studied by combination of potentiometry and UV-VIS spectrophotometry. Stability constants of complexes with selected transition metal ions (Cu2+ , Ni2+ a Zn2+ ) and alkali-earth metals ions (Ca2+ , Mg2+ ) were calculated. Acid-base and coordination properties in the solid state were studied by X-ray diffraction on single-crystals.
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Physico-Chemical Properties of Drugs
Tomanová, Pavla ; Kubíček, Vladimír (advisor) ; Nováková, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of biophysics and physical chemistry Author: Pavla Tomanová Supervisor: Ing. Vladimír Kubíček, CSc. Thesis title: Physico-Chemical properties of drugs This thesis deals with measuring dissociation constants (the pKa value) and the lipophilicity of nitrogenous heterocycle derivatives produced at the Faculty of Pharmacy in Hradec Králové. Two methods were used to determine the pK value: potentiometric titration and spectrophotometry. Potentiometric titration almost invariably produced relatively exact results, however the results of pK value obtained by spectrophotometry were sometimes difficult to replicate. Dissociation constants were compared on the basis of the method applied, and also with the theoretically determined dissociation constant calculated by means of the ChemDraw Ultra 12.0 software. The results obtained by the two experimental methods turned out to be very similar, corresponding to the theoretical pK value. Lipophilicity is another essential property of drugs tested in the preclinical stage. It specifies the aqueous or lipophilic phase affinity of a drug, substantially affecting the drug's ADMET in organism. Lipophilicity was determined on the basis of capacity factor value identified by RP-HPLC measurement using...
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