Thermodynamic and structural studies of the complexation of homocyclopeptides with halide and oxoanions in acetonitrile

U okviru ovog rada proučeni su otopinski kompleksacijski afiniteti homociklopeptida prema halogenidnim i oksoanionima, te prema tiocijanatnom ion, pri čemu je kao otapalo korišten acetonitril. Proučavani ciklopeptidni receptori sadrže pet (L1) odnosno šest (L2) lizinskih podjedinica povezanih u prsten, pri čemu su amino skupine bočnih lanaca zaštićene tert-butiloksikarbonilnom skupinom. Konstante stabilnosti anionskih kompleksa opisanih receptora eksperimentalno su određene pomoću mikrokalorimetrijskih titracija te spektroskopije NMR. Simulacijama molekulske dinamike s eksplicitnim molekulama otapala istražene su strukturne karakteristike veznog mjesta ciklopeptida. Anionski receptori L1 i L2 rijedak su primjer homociklopeptidnih receptora s visokim afinitetom prema anionima u otopini. Provedena su ispitivanja afiniteta te računalne simulacije linearnih peptida prema kloridnom anionu i kationima alkalijskih metala u N,N-dimetilformamidu s ciljem razumijevanja mehanizma reakcije ciklizacije i nastanka ciklopeptidnih receptora. Rezultati istraživanja ukazuju na činjenicu da mehanizam reakcije uključuje koordinaciju aniona, a ne kationa kao što je to do sada bilo smatrano. For the purpose of this thesis, complexation affinities of homocyclopeptides towards halide, thiocyanate and oxoanions in acetonitrile were investigated. Studied cyclopeptide receptors contain five (L1) and six (L2) lysine subunits connected in a macrocycle, with the amino group of the side chains protected by a tert-butyloxycarbonyl group. The binding affinities were investigated experimentally by means of microcalorimetric titrations and NMR spectroscopy while the molecular dynamics simulations were performed to investigate the structural characteristics of the cyclopeptide binding site. Anion receptors L1 and L2 are rare examples of homocyclopeptide receptors with high affinity for anions in solution. Complexation properties studies and computer simulations of linear peptides towards chloride anion and alkali metal cations in N,N-dimethylformamide were conducted to understand the mechanism of cyclization reaction and the formation of cyclopeptide receptors. The study results point to the fact that the reaction mechanism involves anion coordination rather than cation, as it has been previously thought.