Selection of the Parameters in the Synthesis of Ethylenediamine-Folate Using the Plackett Burman Design

https://doi.org/10.22146/ijc.68313

Erianti Siska Purnamasari(1), Linda Septiana(2), Ari Hardianto(3), Ukun Mochammad Syukur Soedjanaatmadja(4), Anni Anggraeni(5), Husein Hernadi Bahti(6*)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(5) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(6) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km 21, Jatinangor 45363, West Java, Indonesia
(*) Corresponding Author

Abstract


This study is concerned with synthesizing ethylenediamine-folate (EDA-Folate), which will then be used as a precursor in synthesizing Gd-PEG-DOTA-Folate, a novel targeted-contrast agent for the diagnosis of cancer, employing the Magnetic Resonance Imaging method. This study aims to determine all the parameters affecting the synthesis of EDA-Folate using the Plackett Burman design. The synthesis method included activation of folic acid using dicyclohexylcarbodiimide and N-Hydroxysuccinimide to result in NHS-Folate, followed by conjugation of ethylenediamine with NHS-Folate to produce EDA-Folate. Analysis of the reaction product confirmed that the reaction product was EDA-Folate. From the resulted data, it can also be concluded that there were four significant parameters (out of the ten parameters studied) in the synthesis of EDA-Folate (with its value presented in the bracket), i.e., time inactivation of NHS-Folate (24 h), stirring rate inactivation of NHS-Folate (300 rpm), the mole of EDA (12 moles), and time of EDA-Folate (12 h). Moreover, the value or desirability of the experimental design was found to be 0.875 (which is < 1.0), meaning that the design will produce optimal conditions and thus the optimal yield of the reaction.


Keywords


ethylenediamine-folate; Plackett-Burman design; yield; contrast agent; Gd-PEG-DOTA-Folate

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DOI: https://doi.org/10.22146/ijc.68313

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