Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan

Three new zinc ions (Zn²⁺) complexes, C¹, C² and Cᶟ, were designed and synthesized by coordination of Zn²⁺into the integrated 1,4,7,10-tetraazacyclododecane (cyclen) and ortho-, meta- and para-bromoxylylguanidinium pendants group. A retrosynthetic analysis was carried out to identify and solve pr...

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Main Author:	Hassan, Nor Amin
Format:	Thesis
Language:	English
Published:	2018
Subjects:	Drugs and their actions Materia medica
Online Access:	https://ir.uitm.edu.my/id/eprint/26963/1/TM_NOR%20AMIN%20HASSAN%20PH%2018_5.pdf
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id	my-uitm-ir.26963
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spelling	my-uitm-ir.269632019-12-27T05:27:30Z Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan 2018 Hassan, Nor Amin Drugs and their actions Materia medica Three new zinc ions (Zn²⁺) complexes, C¹, C² and Cᶟ, were designed and synthesized by coordination of Zn²⁺into the integrated 1,4,7,10-tetraazacyclododecane (cyclen) and ortho-, meta- and para-bromoxylylguanidinium pendants group. A retrosynthetic analysis was carried out to identify and solve problems with regard the selection of organic reactions. The syntheses were performed in five steps including of (i) Gabriel and Ing-Manske primary amine synthesis, (ii) SN2 substitution reaction, (iii) guanylation of primary amine, (iv) deprotection of Boc group, and (v) coordination of Zn²⁺ complex. All the Zn²⁺ complexes structures were characterized by 1H- and 13CNMR spectroscopy, infrared spectroscopy and mass spectrometry. The aim of synthesizing these Zn²⁺ complexes was to confirm the anticipated interactions of Zn²⁺ complexes towards natural DNA as well as to explore the phosphatase activity of such complexes. Hence, ethidium bromide (EB) fluorescence assay and circular dichroism (CD) spectroscopy were used to ascertain the interaction between Zn²⁺ complexes towards natural DNA i.e. calf thymus (ctDNA). The former assay demonstrated a displacement of EB from its complexes with ctDNA, thus confirming the affinity of these Zn²⁺ complexes towards DNA. CD spectroscopic results also revealed that C¹ has disturbed both base stacking and right handed helicity properties of ctDNA, but retained the B-form of its structure. By contrast, C2 and C3 transformed the conformation of ctDNA from B-form into Z-form. This was further supported by thermal denaturation studies showing ATm values of C¹, C², and Cᶟ to be +2, +4 and +5, respectively. The catalytic properties of these complexes for phosphate hydrolysis was evaluated using phosphodiesters bis(p-nitrophenyl)phosphate (BNPP) as a model and monitoring by UV spectrometry. The BNPP hydrolysis results {ca. 17% after 8 days incubation) suggested that C¹, C², and Cᶟ were endowed with still modest yet significant catalytic properties. 2018 Thesis https://ir.uitm.edu.my/id/eprint/26963/ https://ir.uitm.edu.my/id/eprint/26963/1/TM_NOR%20AMIN%20HASSAN%20PH%2018_5.pdf text en public masters Universiti Teknologi MARA Faculty of Pharmacy
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
topic	Drugs and their actions Materia medica
spellingShingle	Drugs and their actions Materia medica Hassan, Nor Amin Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan
description	Three new zinc ions (Zn²⁺) complexes, C¹, C² and Cᶟ, were designed and synthesized by coordination of Zn²⁺into the integrated 1,4,7,10-tetraazacyclododecane (cyclen) and ortho-, meta- and para-bromoxylylguanidinium pendants group. A retrosynthetic analysis was carried out to identify and solve problems with regard the selection of organic reactions. The syntheses were performed in five steps including of (i) Gabriel and Ing-Manske primary amine synthesis, (ii) SN2 substitution reaction, (iii) guanylation of primary amine, (iv) deprotection of Boc group, and (v) coordination of Zn²⁺ complex. All the Zn²⁺ complexes structures were characterized by 1H- and 13CNMR spectroscopy, infrared spectroscopy and mass spectrometry. The aim of synthesizing these Zn²⁺ complexes was to confirm the anticipated interactions of Zn²⁺ complexes towards natural DNA as well as to explore the phosphatase activity of such complexes. Hence, ethidium bromide (EB) fluorescence assay and circular dichroism (CD) spectroscopy were used to ascertain the interaction between Zn²⁺ complexes towards natural DNA i.e. calf thymus (ctDNA). The former assay demonstrated a displacement of EB from its complexes with ctDNA, thus confirming the affinity of these Zn²⁺ complexes towards DNA. CD spectroscopic results also revealed that C¹ has disturbed both base stacking and right handed helicity properties of ctDNA, but retained the B-form of its structure. By contrast, C2 and C3 transformed the conformation of ctDNA from B-form into Z-form. This was further supported by thermal denaturation studies showing ATm values of C¹, C², and Cᶟ to be +2, +4 and +5, respectively. The catalytic properties of these complexes for phosphate hydrolysis was evaluated using phosphodiesters bis(p-nitrophenyl)phosphate (BNPP) as a model and monitoring by UV spectrometry. The BNPP hydrolysis results {ca. 17% after 8 days incubation) suggested that C¹, C², and Cᶟ were endowed with still modest yet significant catalytic properties.
format	Thesis
qualification_level	Master's degree
author	Hassan, Nor Amin
author_facet	Hassan, Nor Amin
author_sort	Hassan, Nor Amin
title	Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan
title_short	Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan
title_full	Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan
title_fullStr	Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan
title_full_unstemmed	Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan
title_sort	design and syntheses of ortho-, meta- and paraxylylguanidinium-zn²⁺- cyclen complexes and their interactions with dna / nor amin hassan
granting_institution	Universiti Teknologi MARA
granting_department	Faculty of Pharmacy
publishDate	2018
url	https://ir.uitm.edu.my/id/eprint/26963/1/TM_NOR%20AMIN%20HASSAN%20PH%2018_5.pdf
_version_	1783733919019958272

Design and syntheses of ortho-, meta- and paraxylylguanidinium-Zn²⁺- cyclen complexes and their interactions with DNA / Nor Amin Hassan

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