Theoretical, spectroscopic, and chromatographic study of the structure and properties of para-substituted 5-benzylidenebarbituric acid derivatives with electron-donor and electron-acceptor substituents

5-Benziliden barbiturati pokazuju različitu biološku aktivnost koja je znatno uslovljena fizičkim, hemijskim i strukturnim osobinama jedinjenja, kao i zanimljive optičke osobine koje su posledica donor-akceptorskih interakcija u molekulu. Sintetisana je serija para-supstituisanih derivata 5-benzilidenbarbiturne kiseline kao potencijalnih push-pull elektronskih sistema sa elektron-donorskim i elektron-akceptorskim supstituentima. Proučavane su donor-akceptorske interakcije, kao i potencijalna elektron-donorska sposobnost barbiturne kiseline u sintetisanim jedinjenjima koja do sada nije potvrđena u literaturi. Elektronske interakcije u jedinjenjima u osnovnom stanju proučavane su LFER analizom NMR podataka, zajedno sa analizom optimizovanih geometrija i izračunatih elektronskih gustina. LSER analizom i TD-DFT proračunima proučavane su ekscitacije i pobuđena stanja. Rezultati "hole-electron" analize i izračunatih ICT deskriptora tokom ekscitacije pokazuju da je p-N(CH3)2 derivat najbolji kandidat za push-pull sistem. Utvrđeno je da barbiturna kiselina može biti slab elektron-donor kada je kuplovana sa jakim elektron-akceptorom. Primenom RP TLC metode određeni su hromatografski parametri lipofilnosti sintetisanih jedinjenja u metanolu, n-propanolu, acetonu i tetrahidrofuranu. Ispitana je zavisnost između hromatografskih parametara lipofilnosti (RМ0 i m), softverski dobijenih vrednosti logP kao standardne mere lipofilnosti, farmakokinetičkih i toksikoloških parametara primenom linearne regresije, klasterske analize i analize glavnih komponenata. Retenciono ponašanje ispitivanih jedinjenja znatno je uslovljeno prirodom supstituenata kao i njihovim elektronskim efektima. Rezultati potvrđuju da se hromatografski parametri, RМ0 i m mogu koristiti za opisivanje lipofilnosti ispitivanih jedinjenja.5-Benzylidenebarbiturates show different biological activities that are significantly influenced by the physical, chemical, and structural properties of the compound, as well as interesting optical properties resulting from donor-acceptor interaction in the molecules. A series of para-substituted 5-benzylidenebarbituric acid derivatives as potential push-pull electronic systems with electron-donor and electron-acceptor substituents was synthesized. The potential electron-donor abilities of barbituric acid, which are still not established in the literature, and donor-acceptor interactions in the synthesized compounds were investigated. The electronic interactions in the ground state were investigated by LFER analysis on 13C NMR data together with the analysis of optimized geometries and calculated electron densities. The electron excitations and the nature of excited state were studied by LSER analysis and TDDFT calculations. The results of the “hole-electron” analysis and calculated ICT descriptors during the excitation show that the p-N(CH3)2 derivative is the best candidate for the push-pull system. It has been found that barbituric acid can be a weak electron-donor when coupled with a strong electron-acceptor. The chromatographic lipophilicity parameters of the synthesized compounds were determined by the RP TLC in methanol, n-propanol, acetone, and tetrahydrofuran. The relationship between chromatographic lipophilicity parameters (RМ0 and m), theoretically calculated logP values as a standard measure of lipophilicity, pharmacokinetic and toxicological parameters was examined using the linear regression, cluster analysis, and principal component analysis. The retention behavior of the investigated compounds is significantly conditioned by the nature of the substituents as well as their electronic effects. The results confirm that the chromatographic parameters (RМ0 and m) can be used to describe the lipophilicity of the investigated compounds