12 research outputs found
Preparation and characteristics of novel anionic sensors based on guanidine subunit
U ovom radu ispitani su sintetski putevi priprave anionskih senzora temeljenih na benzoilgvanidinskoj podjedinici. Na dobivenim spojevima ispitivana je interakcija s odabranim anionima u acetonitrilu, smjesi otapala acetonitril-voda te u vodi. Promjene su praÄene u UV podruÄju.
RaÄunskom DFT metodom su optimirane strukture spojeva te je odreÄena pKa vrijednost za protoniranu formu spojeva. Dodatno je na nekim primjerima raÄunski simuliran UV spektar da bi se pobliže istražilo koja jedinka najviÅ”e pridonosi izgledu UV spektra.
Pokazano je da interakcija izmeÄu senzora i aniona ovisi o njihovim kiselo-baznim svojstvima. Ispitivanjem utjecaja vode na ovakvim sustavima ustanovljeno je da voda otežava interakciju anion-gvanidinijev kation te da voda bez prisustva aniona uzrokuje sliÄnu promjenu UV spektra, ispitivanih spojeva, kao i anioni.In this master thesis, synthetic pathways for the preparation of anionic sensors based on the benzoylguanidine subunit were tested. The compounds obtained were subjected to interaction with the selected anions in acetonitrile, a mixture of acetonitrile-water and water. Changes were monitored in the UV area.
With the computational DFT method the structures of the compounds were optimized and pKa values were determined for the protonated forms of the compounds. In some instances, a computationally simulated UV spectrum is used to investigate which of the structures is the one that contributes most to the appearance of the UV spectrum.
It has been shown that interaction between sensors and anions depends on their acid-base properties. By examining the influence of water on such systems, it was found that water inhibits the interaction of anion-guanidinium cation and that water without the presence of anion causes a similar change in UV spectrum as anions
Computational Study of Electronic Influence of Guanidine Substitution on Diels-Alder Reactions of Heterocyclic Dienes
Quantum-chemical calculations of cycloaddition properties of cyclic heterodienes substituted with guanidine functionality were carried out. Molecular and electronic structures of series of dienes (pyrrole, furan, thiophene, isoindole and 1,3-butadiene) were calculated and reactivity order established on the basis of FMO theory. Transition state calculations of model [4+2] cycloaddition reaction with acetylene indicate that guanidine substitution influences reaction barriers in moderate extent (up to ~4 kcal molā1). The substitution position plays an important role on the sign and magnitude of the effect and protonation of nitrogen possessing substituents increases reactivity of dienes.
This work is licensed under a Creative Commons Attribution 4.0 International License
Anion-Controlled Synthesis of Novel Guanidine-Substituted Oxanorbornanes
The cycloaddition of simple alkyl-substituted guanidine derivatives is an interesting approach toward polycyclic superbases and guanidine-based organocatalysts. Due to the high nucleophilicity of guanidines, an aza-Michael reaction with dienophiles is more common and presents a huge obstacle in achieving the desired synthetic goal. Our preliminary investigations indicated that the proton could act as a suitable protecting group to regulate the directionality of the reaction. To investigate the role of the protonation state and type of anion, the reactivity of furfuryl guanidines with dimethyl acetylenedicarboxylate was explored. Furfuryl guanidines showed a strong reaction dependence on the nucleophilicity of the counterion and the structure of guanidine. While the reaction of DMAD with the guanidinium halides provided products of an aza-Michael addition, DielsāAlder cycloaddition occurred if non-nucleophilic hexafluorophosphate salts were used. Depending on the structure and the reaction conditions, oxanorbornadiene products underwent subsequent intramolecular cyclization. A tendency toward intramolecular cyclization was interpreted in terms of the pKa of different positions of the guanidine functionality in oxanorbornadienes. New polycyclic guanidines had a slightly decreased pKa in acetonitrile and well-defined geometry suitable for the buildup of selective sensors
Solitary pulmonary amyloidoma mimicking lung cancer on 18F-FDG PET-CT scan in systemic lupus erythematosus patient
Localized amyloid deposits (tumoral amyloidosis or amyloidoma) are uncommon form of amyloidosis and nodular pulmonary amyloidomas are rarely found. This incidental finding can mimic a bronchopulmonary neoplasm and may occur secondarily to an infectious, inflammatory or lymphoproliferative disease. We report a case of a 62-year-old female with long-standing systemic lupus erythematosus (SLE) with low compliance who presented with radiologically-verified solitary pulmonary nodule. Work-up included positron emission tomography-computed tomography (PET-CT) scan, which revealed hypermetabolic uptake of (18)F-fluorodeoxyglucose, and lobectomy was performed. Staining of the tissue was positive for Congo red and was green birefringent under polarized light. Immunohistochemical methods excluded lymphoproliferative disease and confirmed amyloidoma. SLE was controlled with antimalarials and glucocorticoids. Pulmonary amyloidoma should be considered in the differential diagnosis of solitary lung nodules
Synthesis and properties of guanidine cocatalysts prepared by cycloadition reactions
U sklopu ove disertacije razvijene su metode za sintezu novih polickliÄkih gvanidina. Pri
tome je istražen utjecaj strukture gvanidinske skupine i tipa dienofila na uspjeŔnost reakcije
cikloadicije i moguÄa uloga protona kao zaÅ”titne skupine. Derivati maleinske kiseline daju
smjesu egzo i endo produkata neovisno o primijenjenom sintetskom pristupu. Cikloadicija
furfuril-gvanidina na dimetil-acetilendikarboksilat daje ciljane produkte u dobrim prinosima
uz djelomiÄnu konverziju u tri- ili tetracikliÄke derivate. ObjaÅ”njena je i pojava aza-
Michaelove adicije kao nusreakcije uzrokovane nukleofilnoÅ”Äu aniona. Mehanizmi reakcija su
istraženi i DFT kvantno kemijskim proraÄunima.
Novim spojevima je ispitana kokatalitiÄka aktivnost u aldolnoj reakciji kataliziranoj (S)-prolinom. Opaženo je poveÄanje selektivnosti i iskoriÅ”tenja reakcije pri Äemu se istiÄe rezultat od 98:2 omjer dijastereoizomera, uz enantiomerni suviÅ”ak >99,5 % i prinosom
od 97 % pri 0Ā°C. Najbolji kokatalizator je ispitan u Knoevenagelovoj reakciji gdje je primijeÄena slaba
aktivnost, znaÄajno manja nego kod strukturno sliÄnog 1,5,7-triazabiciklo[4.4.0]dec-1-ena.As part of this dissertation, methods for the synthesis of new polycyclic guanidines were
developed. The influence of the guanidine structure and the type of dienophile on the success
of the cycloaddition reaction and the possible role of protons as a protective group were
investigated. Maleic acid derivatives give a mixture of exo and endo products regardless of
the synthetic methods employed. The cycloaddition of furfuryl-guanidine to dimethyl
acetylenedicarboxylate produces the target products together with three- or tetracyclic
derivatives in good yields. Aza-Michael addition as a side reaction caused by the
nucleophilicity of anions is also explained. Reaction mechanisms were investigated by DFT
quantum chemical calculations.
The cocatalytic activity of the new compounds was tested in aldol reaction catalyzed by (S)-proline.
An increase in the selectivity and yield of the reaction was observed, with the best
result of 98:2 diastereoisomer ratio, with an enantiomeric excess of >99.5% and a yield of
97% at 0 Ā°C. The best cocatalyst was tested in the Knoevenagel reaction where a poor
activity, significantly lower than for 1,5,7-triazabicyclo[4.4.0]dec-1-ene, was observed
Synthesis and properties of guanidine cocatalysts prepared by cycloadition reactions
U sklopu ove disertacije razvijene su metode za sintezu novih polickliÄkih gvanidina. Pri
tome je istražen utjecaj strukture gvanidinske skupine i tipa dienofila na uspjeŔnost reakcije
cikloadicije i moguÄa uloga protona kao zaÅ”titne skupine. Derivati maleinske kiseline daju
smjesu egzo i endo produkata neovisno o primijenjenom sintetskom pristupu. Cikloadicija
furfuril-gvanidina na dimetil-acetilendikarboksilat daje ciljane produkte u dobrim prinosima
uz djelomiÄnu konverziju u tri- ili tetracikliÄke derivate. ObjaÅ”njena je i pojava aza-
Michaelove adicije kao nusreakcije uzrokovane nukleofilnoÅ”Äu aniona. Mehanizmi reakcija su
istraženi i DFT kvantno kemijskim proraÄunima.
Novim spojevima je ispitana kokatalitiÄka aktivnost u aldolnoj reakciji kataliziranoj (S)-prolinom. Opaženo je poveÄanje selektivnosti i iskoriÅ”tenja reakcije pri Äemu se istiÄe rezultat od 98:2 omjer dijastereoizomera, uz enantiomerni suviÅ”ak >99,5 % i prinosom
od 97 % pri 0Ā°C. Najbolji kokatalizator je ispitan u Knoevenagelovoj reakciji gdje je primijeÄena slaba
aktivnost, znaÄajno manja nego kod strukturno sliÄnog 1,5,7-triazabiciklo[4.4.0]dec-1-ena.As part of this dissertation, methods for the synthesis of new polycyclic guanidines were
developed. The influence of the guanidine structure and the type of dienophile on the success
of the cycloaddition reaction and the possible role of protons as a protective group were
investigated. Maleic acid derivatives give a mixture of exo and endo products regardless of
the synthetic methods employed. The cycloaddition of furfuryl-guanidine to dimethyl
acetylenedicarboxylate produces the target products together with three- or tetracyclic
derivatives in good yields. Aza-Michael addition as a side reaction caused by the
nucleophilicity of anions is also explained. Reaction mechanisms were investigated by DFT
quantum chemical calculations.
The cocatalytic activity of the new compounds was tested in aldol reaction catalyzed by (S)-proline.
An increase in the selectivity and yield of the reaction was observed, with the best
result of 98:2 diastereoisomer ratio, with an enantiomeric excess of >99.5% and a yield of
97% at 0 Ā°C. The best cocatalyst was tested in the Knoevenagel reaction where a poor
activity, significantly lower than for 1,5,7-triazabicyclo[4.4.0]dec-1-ene, was observed
Synthesis and properties of guanidine cocatalysts prepared by cycloadition reactions
U sklopu ove disertacije razvijene su metode za sintezu novih polickliÄkih gvanidina. Pri
tome je istražen utjecaj strukture gvanidinske skupine i tipa dienofila na uspjeŔnost reakcije
cikloadicije i moguÄa uloga protona kao zaÅ”titne skupine. Derivati maleinske kiseline daju
smjesu egzo i endo produkata neovisno o primijenjenom sintetskom pristupu. Cikloadicija
furfuril-gvanidina na dimetil-acetilendikarboksilat daje ciljane produkte u dobrim prinosima
uz djelomiÄnu konverziju u tri- ili tetracikliÄke derivate. ObjaÅ”njena je i pojava aza-
Michaelove adicije kao nusreakcije uzrokovane nukleofilnoÅ”Äu aniona. Mehanizmi reakcija su
istraženi i DFT kvantno kemijskim proraÄunima.
Novim spojevima je ispitana kokatalitiÄka aktivnost u aldolnoj reakciji kataliziranoj (S)-prolinom. Opaženo je poveÄanje selektivnosti i iskoriÅ”tenja reakcije pri Äemu se istiÄe rezultat od 98:2 omjer dijastereoizomera, uz enantiomerni suviÅ”ak >99,5 % i prinosom
od 97 % pri 0Ā°C. Najbolji kokatalizator je ispitan u Knoevenagelovoj reakciji gdje je primijeÄena slaba
aktivnost, znaÄajno manja nego kod strukturno sliÄnog 1,5,7-triazabiciklo[4.4.0]dec-1-ena.As part of this dissertation, methods for the synthesis of new polycyclic guanidines were
developed. The influence of the guanidine structure and the type of dienophile on the success
of the cycloaddition reaction and the possible role of protons as a protective group were
investigated. Maleic acid derivatives give a mixture of exo and endo products regardless of
the synthetic methods employed. The cycloaddition of furfuryl-guanidine to dimethyl
acetylenedicarboxylate produces the target products together with three- or tetracyclic
derivatives in good yields. Aza-Michael addition as a side reaction caused by the
nucleophilicity of anions is also explained. Reaction mechanisms were investigated by DFT
quantum chemical calculations.
The cocatalytic activity of the new compounds was tested in aldol reaction catalyzed by (S)-proline.
An increase in the selectivity and yield of the reaction was observed, with the best
result of 98:2 diastereoisomer ratio, with an enantiomeric excess of >99.5% and a yield of
97% at 0 Ā°C. The best cocatalyst was tested in the Knoevenagel reaction where a poor
activity, significantly lower than for 1,5,7-triazabicyclo[4.4.0]dec-1-ene, was observed
Catastrophic antiphospholipid syndrome associated with systemic lupus erythematosus treated with rituximab: case report and a review of the literature
Catastrophic antiphospholipid syndrome (CAPS) is a rare, acute, life-threatening form of antiphospholipid syndrome. In the last several decades there has been a significant improvement in the treatment of patients with CAPS, but the overall mortality is still very significant. The use of rituximab has been reported in the treatment of refractory cases of CAPS but the data are still scarce and inconclusive. We report a case of 47-year old male patient with long standing SLE and secondary APS who presented with acute thromboembolic incident (partial thrombosis of superior mesenteric artery). During the first week of his hospitalization he met the criteria for probable CAPS. He was treated with anticoagulants, glucocorticoids, intravenous immunoglobulins and systemic antibiotics. Finally he was treated with rituximab. There was no response to the implemented treatment and he eventually died. Autopsy showed evidence of small vessel thrombosis in the lung microvasculature. With this the criteria for definitive CAPS were fulfilled. To our knowledge, at present time, this is the first ever reported case of definitive CAPS associated with SLE treated with rituximab. There is a great need for further investigation to evaluate the effectiveness of rituximab in treatment of CAPS