Otvaranje i deprotoniranje tiazolidinskog prstena. Računalna DFT studija

Abstract

Thiazolidine, a long-known and thoroughly tested molecule, is a structural part of many commonly used compounds. Among these are penicillin antibiotics, which can be found in the environment in increasing concentrations that already exhibit a number of harmful effects in both environmental and health aspects. In order to find a solution for this problem, in the laboratory where this thesis was made it was discovered that UV light only opens thiazolidine ring in thiazolidine and its derivatives. This discovery requires additional chemical description that cannot be obtained through experiments. Therefore, in this research computational methods were used to gather chemical descriptors for the mentioned process on thiazolidine and its three derivatives. For each derivative, species with open and closed thiazolidine rings were tested, as well as certain constants that describe the transition from one species to another. All collected results in this work were calculated using Gibbs free energies of optimized structures at b3lyp/6-31G(d,p) and b3lyp/6-311++G(d,p) theoretical level. Solvation energies were obtained using the SMD method. Acidity constants were calculated using six different methods, of which method 5 proved to be the most accurate one. Transition state structure for thiazolidine ring-opening reaction was confirmed by IRC calculation, and the wavelengths of absorption maxima were confirmed by TD-DFT calculations. The obtained values for acidity and chemical equilibrium constants give a basic insight into the behavior of tested species in water. Global reactivity indexes, accompanied by UV-Vis absorption maxima, show high reactivity for all examined compounds. For all molecules, the ratio of the constants values for the same reactions among the corresponding species is the same. The constants' absolute values for the molecules obtained differ depending on the substituents on the thiazolidine ring, as expected.Tiazolidin, dobro poznata i temeljito ispitana molekula, strukturalni je dio mnogih, često korištenih spojeva. Među takvima su i penicilinski antibiotici, koje nalazimo u okolišu u sve većim koncentracijama koje već sada uzrokuju niz štetnih učinaka u ekološkom i zdravstvenom aspektu. S ciljem pronalaska rješenja za ovaj aktualni problem, u laboratoriju gdje je izrađen ovaj rad otkriveno je da pod utjecajem UV svjetla dolazi do otvaranja tiazolidinskog prstena u tiazolidinu i njegovim derivatima. Ovo otkriće zahtijeva dodatno razumijevanje koje se eksperimentima za ovaj brzi proces ne može dobiti. U tu su svrhu u ovom radu korištene računalne metode te su dobiveni kemijski parametri koji opisuju spomenuti proces na tiazolidinu i trima njegovim derivatima. Za svaki su derivat ispitane specije s otvorenim i zatvorenim tiazolidinskim prstenom, te određene konstante koje opisuju prelazak jedne specije u drugu. Svi prikupljeni rezultati ovog rada izračunati su pomoću slobodnih Gibbsovih energija optimiziranih struktura na b3lyp/6-31G(d,p) i b3lyp/6-311++G(d,p) teorijskoj razini. Solvatacijske energije dobivene su pomoću SMD metode. Konstante kiselosti izračunate su pomoću šest različitih metoda, od kojih se metoda 5 pokazala najtočnijom. IRC računom potvrđena je struktura prijelaznog stanja reakcije otvaranja tiazolidinskog prstena, a TD-DFT računima valne duljine apsorpcijskih maksimuma. Dobivene vrijednosti konstanti kiselosti i kemijske ravnoteže daju osnovni uvid u ponašanje specija u vodi. Indeksi reaktivnosti, popraćeni UV-Vis apsorpcijskim maksimumima, pokazuju visoku reaktivnost svih ispitivanih spojeva. Za sve molekule, odnos vrijednosti pojedinih konstanti za iste reakcije među odgovarajućim specijama je isti. Apsolutna vrijednost dobivenih brojki razlikuje se ovisno o supstituentima na tiazolidinskom prstenu, kao što je i očekivano