페나진 유도체의 반응성과 항균성에 대한 양자 화학적 연구 = Quantum Chemical Studies for the Reactivity and Antimicrobial Activity of Phenazine Derivatives

국문 초록 (Abstract)

그람 양성균과 그람 음성균에 대해 항균성을 가지며 7번 위치에 하이드록시기, 메톡시기, 메틸기, 아세틸기, 니트로기가 치환된 7-substituted 2,3-dihydroxy phenazine-5,10-dioxide 유도체들의 반응 부위의 예측과 항균성을 해석하기 위하여 ab initio 법으로 양자 화학적인 연구를 하였다. 최적화된 유도체들의 구조로부터 얻어진 frontier 오비탈과 frontier 에너지로부터 얻어진 결과는 유도체들은 친전자적인 분자였으며, 최적화된 페나진 고리 평면과 수직을 이루는 각 원자의 p오비탈이 주로 반응에 관여하고, 페나진 고리 속에 포함되어있는 질소 원자와 질소 원자와 결합한 산소가 친핵성 반응, 친전자성 반응, 친라디칼성 반응이 일어나는 주요 부위라는 결과를 얻었다. 그리고 5번 질소와 결합 된 산소의 친핵 frontier 밀도가 작을수록, 10번 질소와 결합한 산소의 친핵 frontier 밀도가 값이 클수록 유도체들이 가지는 항균력은 우세하였다. 연구의 결과는 새로운 페나진 유도체의 합성이나 효과적인 의약품의 설계에 유용한 정보들이다.

다국어 초록 (Multilingual Abstract)

A quantum chemical study for the reactivity site and antimicrobial activity of 7-substituted 2,3-dihydroxy phenazine-5,10-dioxide derivatives, which substituent are hydroxy, methoxy, methyl, acethyl and nitro group, known as antimicrobial agent, were investigated by ab initio method. The results obtained from the frontier orbital and frontier energy showed that the derivatives were electrophilic molecules, and the p orbitals of oxygen, nitrogen and carbon perpendicular to the optimized phenazine plane were mainly involved in the reaction. And it was found that the nitrogen atom in the phenazine ring and oxygen bonded to the nitrogen atom were the main sites where nucleophilic reactions, electrophilic reactions and radical reactions took place. As the nucleophilic frontier density of oxygen bound to nitrogen 5 was lower and it of oxygen bound to nitrogen 10 was higher, the antimicrobial activity of the derivatives was dominant. The results of this studies are useful information for the synthesis of new phenazine derivatives or the design of effective pharmaceuticals.

목차 (Table of Contents)

• 1. 서론 2. 이론 및 계산 3. 결과 및 고찰 참고문헌

참고문헌 (Reference)

1 이만길, "페나진 유도체의 합성과 항균성 : 7-처환-2, 3-디히드록시페나진-5, 10-디옥시드류의 합성 및 항균성" 36 (36): 440-, 1992

2 은재순, "임상약리학" 현문사 259-, 2007

3 박병각, "양자화학" 광림사 343-, 1994

4 이길준, "벤즈이미다졸 치환체들의 분자 특성에 대한 연구" 국방안보연구소 4 (4): 91-99, 2020

5 Berneth, H., "Ullmann's Encyclopedia of Industrial Chemistry" Wiley-VCH 2012

6 Viktorsson, E. Ö., "Total synthesis and antileukemic evaluations of the phenazine 5,10-dioxide natural products iodinin, myxin and their derivatives" 25 (25): 2285-, 2017

7 Nanasthit, A., "Synthesis, isolation of phenazine derivatives and their antimicrobial activities" 6 (6): 79-, 2009

8 Lavaggi, M. L., "Structural modifications on the phenazine N,N -dioxide-scaffold looking for new selective hypoxic cytotoxins" 45 (45): 5362-, 2010

9 McQuarrie, D. A., "Sausalito" University Science Books 411-, 1997

10 Exner, O., "Resonance energy in benzene and ethene derivatives in the gas phase as a measure of resonance ability of various functional groups" 2 (2): 1994-, 2000

11 韓盛旭, "Phenazine 誘導體의 合成과 抗菌性에 미치는 置換基 效果" 嶺南大學校 大學院 1988

12 Alan, G., "Phenazine dyes"

13 Huigens, W., "Phenazine derivatives as antimicrobial agents"

14 Gonda, M., "Phenazine N,N -dioxide scaffold as selective hypoxic cytotoxin pharmacophore. Structural modifications looking for further DNA topoisomerase II-inhibition activity" 4 : 595-, 2013

15 Ayers, P. W., "Perturbative perspectives on the chemical reaction prediction problem" 101 : 520-, 2005

16 Lavaggi, M. L., "Novel phenazine 5,10-dioxides release OH in simulated hypoxia and induce reduction of tumour volume in vivo" 2011 : 11-, 2011

17 Pierson, L. S., "Metabol -ism and function of phenazines in bacteria: Impacts on the behavior of bacteria in the environment and biotechnological processes" 86 (86): 1659-, 2010

18 Aust, A. E., "Mechanisms of DNA oxidation" 222 (222): 246-, 1999

19 Blagoi, Y. P., "Investigation of phenazine derivatives interaction with DNA by polarized fluorescence method" 13 (13): 22-, 1997

20 Fukui, K., "Frontier orbitals and reaction paths selected papers of Kenichi Fuku" World Scientific 1997

21 Levine, I. N., "Englewood Cliffs" Prentice Hall 455-, 1991

22 Parr, R. G., "Electrophilicity index" 121 : 1922-, 1999

23 Parr, R. G., "Electronegativity the density functional viewpoint" 68 : 3801-, 1978

24 Gazquez, J. L., "Electrodonating and electroaccepting powers" 111 : 1966-, 2007

25 Chowdhury, G., "DNA strand cleavage by the phenazine Di-N-oxide natural product myxin under both aerobic and anaerobic conditions" 25 : 197-, 2012

26 Williams, N. H., "DNA Hydrolysis Mechanism and Reactivity. Artificial Nucleases" 13 : 3-, 2004

27 Stewart, J. J. P., "Computation chemistry" VCH 328-, 1990

28 Brown, R. D., "Charge-transfer complexes and the mechanism of aromatic substitution. Part I.General theory" 2224-, 1959

29 Pachon, G., "Antitumoral effect of phenazine N5 , N10: dioxide derivatives on caco-2 Cells" 21 (21): 1578-, 2008

30 Vukomanovic, D., "Antimicrobial phenazine com: Pounds"

31 Fukui, K., "Advanced in quantum chemistry" Academic Press 6-177, 1972