ULOGA NEKOVALENTNIH INTERAKCIJA FLUORA U PAKOVANJU MOTIVA: ANALIZA KRISTALOGRAFSKIH PODATAKA I KVANTNO-HEMIJSKI PRORAČUNI

Abstract

Nekovalentne interakcije imaju značajnu ulogu u formiranju supramolekulskog kristalnog pakovanja molekula. Interakcije koje uključuju atome halogena obezbeđuju slabo, ali visoko usmerenu kontrolu pakovanja molekula u čvrstom stanju. Uvođenje F-atoma može dovesti do značajnih promena u 2D ili 3D strukturama [1], povećanja stabilnosti biomolekula [2] ili poboljšanja dizajna lekova [3]. Da bi se ispitao efekat supstitucije H-atoma F-atomom, sintetisana su i strukturno okarakterisana dva derivata hidantoina: C15H16N2O3 (1) i C15H15N2O3F (2) (slika). Analiza kristalnih pakovanja 1 i 2 pokazala je da su NH…O i CH…O vodonične veze najbrojnije. U strukturi 2 se zbog fluorovanja povećava broj interakcija cikloheksilnog (Ch) i fenil-grupe (Ph) prstena (CH…π interakcije), kao i između dva Ph prstena (π-π interakcije). Kvantno-hemijski proračuni na model sistemima koji predstavljaju dimere derivata hidantoina i izolovanih cikličnih jedinjenja, pokazali su da fluorovanje utiče na stvaranje jačih CH…π i π-π interakcija. Atom F u 2 učestvuje u formiranju tri CH…F i jedne F…F interakcije, što je u saglasnosti sa rezultatima Kembridžke baze podataka, koji su pokazali da su najbrojnije CH…F i F…F interakcije, a njihova jačina dostiže vrednost 2 kcal∙mol–1. Kristalogafski podaci: 1, P–1, a = 6,3079(13), b = 10,573(2), c = 11,415(2) Å, α = 67,21(3), β = 78,84(3), γ = 76,16(3)°, R1 = 6,06%; 2, P–1, a = 5,9981(12), b = 11,148(2), c = 12,073(2) Å, α = 108,98(3), β = 101,57(3), γ = 105,27(3)°, R1 = 4,82%.

Non-covalent interactions have a significant role in supramolecular crystal packings of the molecules. Halogen interactions provide weak but highly directed control of the packing of molecules in the solid state. Introduction of F atom can leads to significant differences in 2D or 3D structures [1], higher structural stability of biomolecules [2] or improve drug design [3]. In order to examine the substitution effect of H atom with F atom, two hydantoin derivatives were synthesized and structurally characterized: C15H16N2O3 (1) i C15H15N2O3F (2) (Figure). Crystallographic analysis of 1 and 2 showed that NH…O and CH…O hydrogen bonds are the most numerous in their crystal packings. Due to fluoridation in 2, the number of interactions among cyclohexyl (Ch) and phenyl ring (Ph) rings (CH…π interactions), as well as among two Ph rings (π-π interactions) is increased. Quantum-chemical calculations on the model systems presented by dimmers of hydantoin derivatives and isolated cyclic compounds, verified that fluoridation caused the formation of stronger CH…π and π-π interactions. The F atom in 2 is involved in three CH…F and one F…F interactions, which is in agreement with the results from the Cambridge Structural Database, which have shown that CH…F and F…F interactions are the most numerous, and their strength reaches the value of 2 kcal∙mol–1. Crystallographic data: 1, P–1, a = 6.3079(13), b = 10.573(2), c = 11.415(2) Å, α = 67.21(3), β = 78.84(3), γ = 76.16(3)°, R1 = 6.06%; 2, P–1, a = 5.9981(12), b = 11.148(2), c = 12.073(2) Å, α = 108.98(3), β = 101.57(3), γ = 105.27(3)°, R1 = 4.82%.