Date of Award


Document Type


Degree Name

MS in Chemistry



First Advisor

Steven Graham

Second Advisor

Joseph Serafin

Third Advisor

Philips Lukeman


N1-cyclic inosine 5’-diphosphate ribose, another class of the well-known calcium second messenger cyclic adenosine 5’-diphospate ribose, reveals nearly identical concentration-response calcium releasing activity intracellularly in a Jurkat T-cells (JTC) system. In this study, a three steps synthetic route is proposed to synthesize cIDPR analog 8-bromo-N1-cIDPR (8-Br-N1-cIDPR), the first 8-substitued analog has agonistic activity. The structure-activity relationship (SAR) of this messenger was investigated by the knowledge of its conformational landscapes, determined by variable-temperature NMR spectroscopy, in conjunction with PSEUROT and population analysis, allowing the study of thermodynamic parameters. A pure in-phase (PIP) heteronuclear correlation NMR experiment was adopted for direct extraction of coupling constants of non-first order proton signals. 8-Br-N1-cIDPR in many ways shows the opposite thermodynamics compared to cADPR analogs, despite its clear agonistic behavior.