Publication: Synthesis and structural characterization of new dithiophosphonic acids, derivatives and complexes from 2,4-diorganyl-1,3,2,4- dithiadiphosphetane-2,4-disulfide
Abstract
Dimer olarak bilinen yeni 2,4-bis(Rx,y)-1,3,2,2,4-ditiyadifosfetan-2,4-disülfürü ([Rx,y-P(S)S]2, Rx= 3,4-dimetoksifenil, SAV-A1; Ry= 2,4-dimetoksifenil, SAV-A2) başlangıç maddesi olarak sentezlenmiştir. Bu dimerlerin alkol ile reaksiyonundan (16 adet) ditiyofosfonik asitler, [Rx,y(RnO)P(S)SH] sentezlenmiştir. Bu asitlerden 12 tanesi, [Rx(RnO)P(S)SH], SAV-A1’in alkollerle reaksiyonundan elde edilmiştir (Kısım Ia’da DTPOA sentez çalışması için kullanılan alkoller RnOH, R1=metil-, R2=Etil-, R3=n-propil-, R4=n-butil-, R5=3-pentil-, R6=3-metil-1-butil-, R7=benzil-; Kısım Ib’de DTPOA sentez çalışması için kullanılan alkoller RnOH, R1= -n-pentil; R2=2-pentil-; R3=4-tert-but-benzil-; R4= 2-propil-; R5= 2-butil-). Benzer şekilde (Ry)(RnO)PS2H) olarak adlandırılan SAV-A2’nin alkollerle (Kısım II’de DTPOA sentez çalışması için kullanılan alkoller RnOH, R1= 2-bütil; R2= n-pentil-; R3= 4-tert-butil benzil-; R4= metil-) reaksiyonundan diğer asitler elde edilmiştir. Tüm asitler yapısı belirlenebilir ve kokusuz amonyum ditiyofosfonat tuzuna ([NH4][S2P(Rx)(ORn)] ve [NH4][S2P(Ry)(ORn)]) dönüştürülmüştür (16 Adet). Bu tuzlar Ni(II) iyonuyla reaksiyona girerek dört koordinasyonlu Ni(II) ditiyofosfonata kompleksleri ([Ni(S2P(Rx)(ORn)] ve [Ni(S2P(Ry)(ORn)]) sentezlenmiştir. Tez kapsamında toplam 50 bileşik sentezlenmiştir. Bu çalışmada, sentezlenen yeni bileşiklerin yapısal karakterizasyonu elementel analiziyle beraber kütle, FT-IR, tek ve iki boyutlu NMR (1H-, 13C- ve 31P-NMR) spektroskopileriyle aydınlatılmıştır. Ayrıca, komplekslerin yapısı X-ışını kırınımı yöntemi ile aydınlatıldı ([Ni(S2P(Rx)(ORn)] X ışını analizleri kompleksleri için MÜ, BAP-FDK-2021-10339 projesiyle desteklendi; Part Ia kapsamında n= 1,2,3,4,6,7 ve Part 1b kapsamında n= 1,2,4,5). Komplekslerin teorik hesaplamalarıyla (Density Functional Theory, Molecular Docking) beraber uygulama olarak bileşiklerin antikanser çalışmalarıda gerçekleştirilmiştir.
Two new 2,4-bis(Rx,y)-1,3,2,4-dithiadiphosphetane-2,4-disulfide known as dimer was synthesised as starting material ([Rx,y-P(S)S]2, Rx= 3,4-dimethoxyphenyl, SAV-A1; Ry= 2,4-dimethoxyphenyl, SAV-A2). From the reaction of these dimers with 16 alcohols were synthesized new dithiophosphonic acids ([Rx,y(RnO)P(S)SH]). 12 of these acids ([Rx(RnO)P(S)SH]) were produced from the reaction of SAV1 with alcohols (RnOH= Alcohols used in DTPOA synthesis reactions for Part Ia, R1=methyl-, R2=Ethyl-, R3=n-propyl-, R4=n-butyl-, R5=3-pentyl-, R6=3-methyl-1-butyl-, R7=benzyl-; RnOH= Alcohols used in DTPOA synthesis reactions for Part Ib, RnOH, R1= n-pentyl; R2=2-pentyl-; R3=4-tert-but-benzyl-; R4= 2-propyl-; R5= 2-butyl-). Similarly, other acids which are coded as [Ry(RnO)P(S)SH] were obtained from the reaction of SAV2 with alcohols (RnOH = Alcohols used for Part II for DTPOAs, R1= 2-butyl; R2= n-pentyl-; R3= 4-tert-butyl benzyl-; R4= methyl-). All acids were converted to 16 structurally determinable and odourless ammonium dithiophosphonate salts ([NH4][S2P(Rx)(ORn)] and [NH4][S2P(Ry)(ORn)]). Ni(II) dithiophosphonato complexes were synthesized by the reaction of these salts and Ni(II) ion, as four coordination structures ([Ni(S2P(Rx)(ORn)] and [Ni(S2P(Ry)(ORn)], 16 complexes). Within the scope of the thesis, a total of 50 new compounds were synthesized. This study elucidated the structural characterization of the synthesized new compounds by mass, FT-IR, NMR, (1D 1H-, 13C-, 31P-NMR and 2D HSQC for [Ni(S2P(Rx)(OR6)] and [Ni(S2P(Ry)(OR2)]) spectroscopies together with elemental analysis. In addition, the structure of the complexes was elucidated by the X-ray diffraction method ([Ni(S2P(Rx)(ORn)] X-ray analyses for complexes supported by MÜ, BAP-FDK-2021-10339 project; n= 1,2,3,4,6,7 under Part Ia and n= 1,2,4,5 under Part 1b). Theoretical calculations of the complexes (density functional theory, molecular docking) and anticancer studies of the compounds were carried out as applications.
Two new 2,4-bis(Rx,y)-1,3,2,4-dithiadiphosphetane-2,4-disulfide known as dimer was synthesised as starting material ([Rx,y-P(S)S]2, Rx= 3,4-dimethoxyphenyl, SAV-A1; Ry= 2,4-dimethoxyphenyl, SAV-A2). From the reaction of these dimers with 16 alcohols were synthesized new dithiophosphonic acids ([Rx,y(RnO)P(S)SH]). 12 of these acids ([Rx(RnO)P(S)SH]) were produced from the reaction of SAV1 with alcohols (RnOH= Alcohols used in DTPOA synthesis reactions for Part Ia, R1=methyl-, R2=Ethyl-, R3=n-propyl-, R4=n-butyl-, R5=3-pentyl-, R6=3-methyl-1-butyl-, R7=benzyl-; RnOH= Alcohols used in DTPOA synthesis reactions for Part Ib, RnOH, R1= n-pentyl; R2=2-pentyl-; R3=4-tert-but-benzyl-; R4= 2-propyl-; R5= 2-butyl-). Similarly, other acids which are coded as [Ry(RnO)P(S)SH] were obtained from the reaction of SAV2 with alcohols (RnOH = Alcohols used for Part II for DTPOAs, R1= 2-butyl; R2= n-pentyl-; R3= 4-tert-butyl benzyl-; R4= methyl-). All acids were converted to 16 structurally determinable and odourless ammonium dithiophosphonate salts ([NH4][S2P(Rx)(ORn)] and [NH4][S2P(Ry)(ORn)]). Ni(II) dithiophosphonato complexes were synthesized by the reaction of these salts and Ni(II) ion, as four coordination structures ([Ni(S2P(Rx)(ORn)] and [Ni(S2P(Ry)(ORn)], 16 complexes). Within the scope of the thesis, a total of 50 new compounds were synthesized. This study elucidated the structural characterization of the synthesized new compounds by mass, FT-IR, NMR, (1D 1H-, 13C-, 31P-NMR and 2D HSQC for [Ni(S2P(Rx)(OR6)] and [Ni(S2P(Ry)(OR2)]) spectroscopies together with elemental analysis. In addition, the structure of the complexes was elucidated by the X-ray diffraction method ([Ni(S2P(Rx)(ORn)] X-ray analyses for complexes supported by MÜ, BAP-FDK-2021-10339 project; n= 1,2,3,4,6,7 under Part Ia and n= 1,2,4,5 under Part 1b). Theoretical calculations of the complexes (density functional theory, molecular docking) and anticancer studies of the compounds were carried out as applications.