Evaluation of solvent and substituent effects on absorption spectra of spirohydantoins derived from α-tetralone

A convenient and efficient approach toward the synthesis of six 3-(4-substituted benzyl)-6,7- benzo-1,3-diazaspiro[4.5]decane-2,4-diones (1‒6) by Bucherer-Bergs reaction and further alkylation at position 3 of the hydantoin ring is reported. Further, their chemical structure was confirmed by melting points, elemental analysis, FT-IR, NMR and UV–Vis spectroscopic methods. To gain an insight into interactions which the investigated spirohydantoins establish with their environment, their absorption spectra were recorded in selected solvents of different polarity and the solvent effects on the UV-Vis absorption band positions, intensity and shape, were discussed. Substiuent effects on the solvatochromism of compounds 1−6 were analyzed using the Hammett's equation. Considering the broad applications of hydantoin derivatives, as well as the fact that their relative importance may increase in the future, results obtained in this study serve as a basis for further investigations

Evaluation of solvent and substituent effects on absorption spectra of spirohydantoins derived from alfa-tetralone

A convenient and efficient approach toward the synthesis of six 3-(4-substituted benzyl)-6,7-benzo-1,3-diazaspiro[4.5]decane-2,4-diones (1‒6) by Bucherer-Bergs reaction and further alkylation at position 3 of the hydantoin ring is reported. Further, their chemical structure was confirmed by melting points, elemental analysis, FT-IR, NMR and UV–Vis spectroscopic methods. To gain an insight into interactions which the investigated spirohydantoins establish with their environment, their absorption spectra were recorded in selected solvents of different polarity and the solvent effects on the UV-Vis absorption band positions, intensity and shape, were discussed. Substiuent effects on the solvatochromism of compounds 1−6 were analyzed using the Hammett's equation. Considering the broad applications of hydantoin derivatives, as well as the fact that their relative importance may increase in the future, results obtained in this study serve as a basis for further investigations

Supramolecular association in 3-(4-chlorobenzoyl)-1,3-diazaspiro[4.5]decane-2,4- dione

Синтетисан је дериват циклохексан-5-спирохидантоина и одређена је његова кристална структура. Хијерархијски развој кристалног паковања дискутован је са аспекта кооперативности димерних мотива који настају преко различитих интермолекулских интеракција, и то: јаких N–H···O водоничних веза и слабих C–H···O, C–H···Cl и C–H···π интеракција. Кристално паковање задржава мотив, који се обично среће код деривата хидантоина, у коме су два инверзано оријентисана молекула повезана паром N–H···O водоничних веза. Специфична структурна карактеристика јесу паралелни слојеви дуж ac-равни. Пошто овај мотив повезује сваки други слој, растојање између слојева се наизменично мења. Накнадна анализа Хиршфелдове површине омогућила је разраду квалитативних и квантитативних доприноса интермолекулских интеракција проучаваном кристалном паковању.A derivative of cyclohexane-5-spirohydantoin was synthesized and its crystal structure was determined. The hierarchical development of the crystal packing was discussed through cooperativity of various dimeric motifs associated with the presence of different intermolecular interactions, namely strong N–H···O, and weaker C–H···O, C–H···Cl and C–H···π interactions. The crystal packing retained the motif commonly found in hydantoin derivatives where two molecules related by inversion are linked by a pair of N–H∙∙∙O hydrogen bonds. A hallmark structural feature was a parallel layer arrangement to the ac-plane with alternating perpendicular separation, whereby this motif connect every second layer. An analysis of the Hirshfeld surface further elaborated the qualitative and quantitative contributions of intermolecular interactions to the crystal packing

Sinteza disupstituisanih derivata pirolidin-2,5-diona primenom mikrotalasnog postupka i evaluacija njihovih farmakokinetički relevantnih svojstava

Succinimide (pyrrolidine-2,5-dione) derivatives represent organic compounds with a broad spectrum of pharmacological activity. Succinimide derivatives are well known anticonvulsants (ethosuccinimide, metosuccinimide and fensuccinimide), antipsychotics, sedatives, anticancer and antiviral agents. In this work, using a modified microwave procedure, succinimide derivatives bearing a meta and/or para-substituted phenyl group in position 1 and 4 were synthetized and completely structurally characterized by melting point, FT-IR/ATR, 1H NMR, 13C NMR and UV-Vis spectra and elemental analysis. The position of the absorption maxima of newly synthesized compounds in different solvents is considered from the aspect of specific and nonspecific interactions established between the molecules. The influence of the chemical structure on the pharmacological potential of succinimide derivatives was evaluated using the "rule of five", Veber, Egan and Ghose’s empirical criteria, as well as using different in silico methods. The obtained values of molecular descriptors were then compared with the characteristic values for reference drugs such as methosuccinimide and ethosuccinimide. Calculated molecular descriptors indicate that the investigated compounds fulfill necessary empirical criteria which qualify them as interesting drug candidates.Derivati sukcinimida (pirolidin-2,5-diona) predstavljaju organska jedinjenja širokog spektra farmakološke aktivnosti. Derivati ovog jedinjenja poznati su antikonvulzivi (etosukcinimid, metosukcinimid i fensukcinimid), antipsihotici, sedativi, antikancerogeni i antivirusni agensi. U okviru ovog rada, primenom modifikovanog mikrotalasnog postupka, sintetisani su pirolidin-2,5-dioni koji u položajima 1 i 4 sadrže meta i/ili para-supstituisanu fenil-grupu. Njihova struktura potvrđena je određivanjem temperature topljenja, primenom FT-IR/ATR, 1H NMR, 13C NMR i UV-Vis spektroksopskih metoda i elementarne analize. Položaj apsorpcionih maksimuma novosintetisanih jedinjenja u različitim rastvaračima razmatran je sa apsekta specifičnih i nespecifičnih interakcija koje se uspostavljaju između molekula rastvorene supstance i molekula rastvarača. Uticaj hemijske strukture na farmakološki potencijal derivata pirolidin-2,5-diona, procenjen je primenom „pravila broja pet“, Veberovog, Eganovog i Gozovog emirijskog kriterijuma, kao i primenom različitih in silico metoda. Dobijene vrednosti molekulskih deskriptora potom su upoređene sa vrednostima karakterističnim za referentne lekove kao što su metosukcinimid i etosukcinimid. Dobijene vrednosti molekulskih deskriptora ukazuju da proučavana jedinjenja zadovoljavaju sve empirijske kriterijume neophodne za dalja ispitivanja lekova

Photosensitive azocinnamoyl liquid crystals with a bent core

V prispevku predstavljamo sintezo in karakterizacijo serije tekočih kristalov z upognjeno sredico. Upognjeno sredico sestavljajo 3 benzenski obroči povezani z azocinamoilno skupino in še 2 povezana z fotoobčutljivim AZO mostom. Dolžini stranskih repov so bili v vseh primerih enake (C12H25–), medtem ko smo na centralnem in zunanjih benzenskih obročih z substitucijo funkcionalnih skupin spreminjali električne lastnosti spojin in njihov način spontanega urejanja. V nasprotju z spojino, ki je vsebovala “gole” benzenske obroče smo v primerih z funkcionalnimi skupinami dosegli večjo prostorsko porazdelitev naboja ter nove - drugačne makroskopsko urejene faze. Pri karakterizaciji smo se osredotočili predvsen na efekte fotoizomerizacije. Znano je, da v azocinamoilnih funkcionalnih skupinah prihaja do več fotokemičnih procesov, poleg cis-trans prehoda še do ciklizacije in foto-Fries reorganizacije. Preučili smo fazni diagram tekoče kristalnih faz, ki jih tvorijo te spojine, odkrili da ena izmed spojin tvori zanimivo smektično B7 fazo. UV osvetlitev vzorcev povzroči spremembe v ureditvi, opazili smo, da se v planarno urejenih celicah te spremembe hitre in ponovljive, ter da znižajo temperaturo faznega prehoda iz smektične v nematsko fazo. V poizkusih, kjer je bil material samo nanšen na stekleno povšino, smo opazili tipično Schliren teksturo, katera se je ob UV osvetlitivi stabilizirala in je ostala stabilna tudi po več mesecih. Razlog za to smo pripisali dimerizaciji cinamoilnih funkcionalih grup, ki so preprečile cis-konformaciji da se relaksira nazaj v trans-konformacijo, predvidevamo, da zaradi omejene geometrije takšen proces ni možen v planarnih celicah

Reverzibilni halogen supstituisani benzilidinhidantoinski molekulski prekidači

Molecular switches that can undertake reversible switching between two or more different states due to an external triggering stimulus are employed in the fabrication of various optoelectronic devices and smart materials and also found many applications in sensing, molecular self-assembly and photo-controlled biological systems. Photochromic organic molecules possessing bistable characteristics, represent attractive materials for the design of molecular switches owing to their considerable structural diversity, molecular conformations, electronic structures, and the possibility to reversibly alter from one state to another by external stimulations such as light irradiation. In this article, we explore the potential of halogen substituted benzylidenehydantoin-based molecules as novel light-sensitive materials and their solvatochromic behavior by recording the absorption spectra in the selected solvent set and evaluating effects of the specific and nonspecific solvent–solute interactions on the absorption maxima shifts using linear solvatation energy relationship, i.e. equations proposed by Kamlet-Taft and Katalan.. The preliminary results of this study will be promising starting point for design of novel photoactive materials with a broad spectrum of applications.Molekulski prekidači koji se mogu mogu reverzibilno prevoditi iz jednog stabilnog stanja u drugo pod dejstvom nekog spoljašnjeg faktora, uveliko se primenjuju u proizvodnji različitih optičkih i elektronskih uređaja, pametnih materijala kao i raznovrsnih materijala sa biološkom primenom. Bistabilni fotohromni organski molekuli, predstavljaju akraktivne materijale za proizvodnju molekulskih prekidača zahvaljujući svojoj strukturnoj raznovrsnosti, molekulskim konformacijama, elektronskim karakteristikama i mogućnosti prevođenja iz jednog stabilnog stanja u drugo pod dejstvom svetlosti. U ovom radu, proučavana je mogućnost primene halogen supstituisanih benzilidenhidantoina u proizvodnji fotosenzitivnih materijala kao i njihova solvatohromna svojstva određivanjem odgovarajućih apsorpcionih maksimuma u odabranom setu rastvarača, a takođe su analizirani specifični i nespecifični efekti rastvarača na pomeranje apsorpcionih maksimuma primenom Kamlet-Taftove i Katalanove jednačine. Preliminarni rezultati ovog istraživanja predstavljaju dobru polaznu tačku u dizajniranju novih fotoaktivnih materijala sa širokim spektrom primene

Estimation of drug-likeness properties of selected disubstituted pyrrolidine-2,5-dione derivatives

Succinimide (pyrrolidine-2,5-dione) derivatives are organic compounds with a wide spectrum of pharmacological activities. Analogs of this cyclic ureide are well-known anticonvulsants (ethosuccinimide, metosuccinimide and fensuccinimide), antipsychotics, and sedatives, anticancer and antiviral agents. In this paper, using a modified microwave procedure, two succinimide derivatives were synthetized and completely structurally characterized by melting point, as well as FT-IR/ATR, 1H NMR, 13C NMR and elemental analysis. The impact of chemical structure on the pharmacological potential of succinimide derivatives was evaluated using the pioneering "rule of five", Veber, Egan, and Ghose’s empirical criteria, as well as using different in silico methods. Obtained values of molecular descriptors were compared with the characteristic values for reference drugs such as methosuccinimide and ethosuccinimide. Calculated molecular descriptors suggest that the investigated compounds fulfill necessary empirical criteria which qualify them as interesting drug candidates. The obtained descriptors indicate a high degree of gastrointestinal absorption (98%) of the synthesized succinimide derivatives. They are expected to successfully pass through the blood-brain barrier due to the adequate lipophilicity. Also, depending on the electronic characteristics of the substituents attached to the phenyl core, the studied compounds can act as activators or inhibitors of different cytochrome P450 isoenzymes

In vitro određivanje antioksidativne aktivnosti halkona na bazi ferocena

Ferrocene derivatives are known as antioxidants, antiparasitic, antitumor, antiviral, antibacterial and antifungal agents. In addition to applications in medicinal chemistry and drug design, ferrocene derivatives are of exceptional importance in synthetic organic chemistry, especially in catalytic asymmetric transformations. They are also used in electrochemistry and polymer chemistry, as additives in fuels, as chemosensors in agrochemistry and biosensors of glucose and active components in molecular electronics. To design new antioxidant agents, five ferrocenyl chalcones were synthesized, and fully characterized by melting points, FT-IR, 1H and 13C NMR spectroscopic methods. The synthesized chalcones differ in the nature and the position of the substituent attached to the phenyl group in position 1 of the linear unsaturated carbonyl system. The potential antioxidant activity of the synthesized compounds was evaluated using the ABTS (2,2'-azinobis-(3- ethylbenzothiazoline-6-sulfonic acid) method and IC50 values of the most effective compounds were further determined.Derivati ferocena su poznati antioksidansi, antiparazitici, antitumorni, antivirusni, antibakterijski i antifungalni agensi. Pored primene u medicinskoj hemiji, derivati ferocena su od izuzetnog značaja u sintetičkoj organskoj hemiji, naročito u katalizovanim asimetričnim sintezama. Primenjuju se i u elektrohemiji i hemiji polimera, kao aditivi u gorivima, kao hemosenzori u agrohemiji i biosenzori glukoze i aktivnih komponenata u molekularnoj elektronici. U cilju dizajniranja novih antioksidativnih agenasa, u ovom radu, sintetisano je pet ferocenilhalkona koji su u potpunosti strukturno okarakterisani određivanjem temperature toplenja, FT-IR, 1H i 13C NMR spektroskopskim metodama. Sintetisani halkoni međusobno se razlikuju prema vrsti i položaju supstituenta na fenil-grupi u položaju 1 linearnog nezasićenog karbonilnog sistema. Potencijalna antioksidativna aktivnost ovih jedinjenja procenjena je primenom ABTS (2,2'-azinobis-(3-etilbenzotiazolin-6- sulfonska kiselina) metode i određivanjem IC50 vrednosti najefikasnijih jedinjenja

On the photophysical properties of a liquid crystal dimer based on 4-nitrostilbene: A combined experimental and theoretical study

A new liquid crystal dimer, 1,12-bis(4-(2-(4-nitrophenyl)ethenyl)phenoxy)dodecane, was synthesized and structurally characterized. The compound exhibited enantiotropic nematic phase. The spectroscopic properties were analysed by UV-Vis and fluorescence techniques. Theoretical calculations were used to predict the UV-Vis spectral properties of three isomers and propose a mechanism of conversion between them. The obtained results present a solid basis for the future studies on the stilbene-based liquid crystal dimers, thus affording guidelines for development of a structure-property relationship of these compounds

SUPRAMOLECULAR ASSOCIATION IN 3-(4-CHLOROBENZOYL)-1,3- DIAZASPIRO[4.5]DECANE-2,4- DIONE

Sintetisan je derivat cikloheksan-5-spirohidantoina i određena je njegova kristalna struktura. Hijerarhijski razvoj kristalnog pakovanja diskutovan je sa aspekta kooperativnosti dimernih motiva koji nastaju preko različitih intermolekulskih interakcija, i to: jakih N–H···O vodoničnih veza i slabih C–H···O, C–H···Cl i C–H···π interakcija. Kristalno pakovanje zadržava motiv, koji se obično sreće kod derivata hidantoina, u kome su dva inverzano orijentisana molekula povezana parom N–H···O vodoničnih veza (slika 1). Specifična strukturna karakteristika jesu paralelni slojevi duž ac-ravni (slika 2). Pošto ovaj motiv povezuje svaki drugi sloj, rastojanje između slojeva se naizmenično menja. Naknadna analiza Hiršfeldove površine omogućila je razradu kvalitativnih i kvantitativnih doprinosa intermolekulskih interakcija proučavanom kristalnom pakovanju. Kristalografski podaci 3-(4-hlorbenzoil)-1,3-diazaspiro[4.5]dekan-2,4-diona: C15H15ClN2O3, Mr = 306.7, trikliničan sistem, prostorna grupa P–1, a = 6,2836(13), b = 10,928(2), c = 12,159(2) Å, = 108,19(3), = 99,76(3), = 104,73(3) °, V = 738,4(3) Å3 , Z = 2, F(000) = 320, ρx = 1,380 g cm–3 , μ(Mo Kα) = 0,270 mm–1 . Utačnjavanje sa F 2 (190 parametara) dalo je R1 = 0,0821, wR2 = 0,1157, S = 1,031 za sve podatke i R1 = 0,0548 za 2707 uočenih refleksija sa I ≥ 2σ(I).A derivative of cyclohexane-5-spirohydantoin was synthesized and its crystal structure was determined. The hierarchical development of the crystal packing was discussed through cooperativity of various dimeric motifs associated with the presence of different intermolecular interactions, namely strong N–H···O, and weaker C–H···O, C–H···Cl and C–H···π interactions. The crystal packing retained the motif commonly found in hydantoin derivatives where two molecules related by inversion are linked by a pair of N–H∙∙∙O hydrogen bonds (Figure 1). A hallmark structural feature was a parallel layer arrangement to the ac-plane (Figure 2) with alternating perpendicular separation, whereby this motif connect every second layer. An analysis of the Hirshfeld surface further elaborated the qualitative and quantitative contributions of intermolecular interactions to the crystal packing. Crystal data for 3-(4-chlorobenzoyl)-1,3-diazaspiro[4.5]decane-2,4-dione: C15H15ClN2O3, Mr = 306.7, triclinic system, space group P–1, a = 6.2836(13), b = 10.928(2), c = 12.159(2) Å, = 108.19(3), = 99.76(3), = 104.73(3) °, V = 738.4(3) Å3 , Z = 2, F(000) = 320, ρx = 1.380 g cm–3 , μ(Mo Kα) = 0.270 mm–1 . The refinement on F 2 (190 parameters) yielded R1 = 0.0821, wR2 = 0.1157, S = 1.031 for all data, and R1 = 0.0548 for 2707 observed reflections with I ≥ 2σ(I)