Fluorescent Chemosensors for Anions and Aminobromination of Unsaturated Phosphonates

Abstract

본 연구 논문은 크게 네 부분으로 나누어져 있다. Part A에서는 100% 수용액 (pH = 7.4, 10 mM HEPES) 상에서 GTP에 대한 형광 화학센서로서 작용하는 새로운 이미다졸리움 안트라센 유도체를 연구하였다. 새로운 형광 화학센서는 chelation-enhanced fluorescence quenching (CHEQ) 효과로 GTP를 감지하는 반면에, ATP, ADP, AMP에 대해서는 chelation-enhanced fluorescence (CHEF) 효과를 보였다. 이것을 토대로, 화합물 1은 acetonitrile 용매상에서 1,8-bis-(imidazolylmethyl) anthracene과 (3-bromopropyl)-trimethylammonium bromide를 반응시킨 후, 재결정 (acetonitrile/methanol = 1:1, v/v)으로 70% 수득률로 합성되었다. Part B에서는 두개의 p-nitrophenylurea 그룹이나 두개의 phenylurea 그룹이 안트라센 1,8번 위치에 고정되어 있을 때, fluoride와 pyrophosphate 이온에 대한 새로운 colorimetric sensor 그리고 형광 센서에 대해 연구하였다. 새로운 colormetric sensor는 fluoride 이온을 첨가했을 때 유일하게 색깔변화가 나타났다. Fluoride, pyrophosphate 이온과 안트라센 9번 위치 H사이의 수소결합은 ¹H NMR 실험을 통해서 기본적으로 설명되어졌다. 합성은 이미 알려진 과정을 토대로 합성된 1,8-dinitroanthraquinone에서 시작하였다. 또한 알려진 합성 과정을 통해서 1,8-dinitroanthraquinone에서 1,8-diaminoanthracene을 합성하였다. Methylene chloride 용액상에서 p-nitrophenyl isocyanate와 diaminoanthracene 또는 p-nitrophenyl isocyanate와 1-aminoanthracene을 반응시켜 각각 75%, 80%의 수득률로 1과 3을 얻었다. Phenyl isocyanate도 diaminoanthracene 또는 1-aminoanthracene 반응시켜 각각 82%, 85% 수득률로 2와 4를 얻었다. Part C에서는 rhodamine B를 기본으로 한 새로운 형광 센서 1을 연구하였다. 새로운 형광 센서는 acetonitrile 상에서 다른 금속 이온과 비교하면 Pb^(2+)와 상당한 선택성을 나타냈다. 신호전달 물질은 타고난 소광 금속 이온에 가역적 CHEF (chelation-enhanced fluorescence)효과를 나타냈다. Compound 1은 POCl₃, rhodamine B Base를 반응시켜, 정제과정 없이 얻어진 rhodmine B acid chloride와 (2-Aminoethyl)-bis-(2-pyridylmethyl)amine을 반응시켜 합성되었다. Flash column chromatography (CHCl₃ : MeOH = 9 : 1, v/v)로 정제하여 42% 수득률로 compound 1을 얻었다. Compound 1 구조는 X-ray crystallography, NMR, mass 결과에 의해 확인 되었다. ¹H NMR, ^(13)C NMR, IR, electrospray ionization (ESI) Mass 자료는 compound 1의 결합 상태를 설명하기 위해 이용 되었다. Part D에서는 vinyl phosphonate 1에서 원하는 aminohydroxylation 생성물을 만들어 내기 위해서 cinnamate ester의 전형적인 AA 과정을 따라 N-bromoacetamide가 nitrogen source로 사용 되었다. 처음 실험에서 N-bromoacetamide 1.1당량을 사용하여 여러 가지 용매 tert-butyl alcohol, 1-propanol, acetonitrile과 수용액 1:1 상에서 오랜 시간 (2일) 반응 시켰을 때, 반응물 색은 초록색에서 노란색으로 변했지만, 출발물질 vinyl phosphonate 1은 사라지지 않았다. 반면에, N-bromoacetamide 3.5당량을 첨가 했을 때는 출발물질 vinyl phosphonate가 2시간 이내에 사라졌고, aminohydroxylation 대신 기대하지 않았던 syn-β-amino-α-bromination 생성물이 관찰 되었다. 이것은 MS spectroscopy, ¹H-¹H COSY, ¹H-^(13)C HMQC 2D NMR 분석을 통해 알아 낼 수 있었다.;In the part A, we report for the first time a new water-soluble imidazolium anthracene derivative, which not only differentiates the structurally similar compounds GTP and ATP but also acts as a potential fluorescent chemosensor for GTP in 100% aqueous solution (pH =7.4, 10mM HEPES). Our new fluorescent chemosensor senses GTP by chelation-enhanced fluorescence quenching (CHEQ) effect, whereas it displays a chelation-enhanced fluorescence (CHEF) effect for ATP, ADP and AMP. host 1 was synthesized by the reaction of 1,8-bis-(imidazolylmethyl)anthracene with (3-bromopropyl)-trimethyl ammonium bromide in acetonitrile followed by recrystallization (acetonitrile : methanol = 1 : 1, v/v) in 70% yield. In the part B, we report herein on new colorimetric sensor and fluorescent sensors for fluoride and pyrophosphate ions in which two p-nitrophenylurea groups or two phenylurea groups are immobilized on the 1,8-position of anthracene. A new colorimetric sensor displays a unique color change upon the addition of fluoride ions. Furthermore, unique hydrogen bonds between the 9-H of anthracene with fluoride and pyrophosphate ions are described based on the ¹H NMR experiments. Treating this diaminoanthracene or 1-aminoanthracene with p-nitrophenyl isocyanate in CH₂Cl₂ afforded 1 or 3 in 75% or 82% yield, respectively. Application of similar procedures to phenylisocyanate gave 2 and 4 in 80% and 85% yield, respectively. In the part C, a new fluorescent sensor based on rhodamine B for Pb^(2+) was synthesized. The new fluorescent sensor showed an extreme selectivity for Pb^(2+) over other metal ions examined in acetonitrile. Upon the addition of Pb^(2+), an overall emission change of 100-fold was observed and the selectivity was calculated to be 200 times that of Zn^(2+). The signal transduction occurs via of reversible CHEF (chelation-enhanced fluorescence) with this inherent quenching metal ion. ¹H NMR, ^(13)C NMR, IR, the electrospary ionization (ESI) Mass data were used to explain the binding mode of compound 1 with metal ions. Compound 1 was synthesized by treating rhodamine B with POCl₃, which was followed without purification by (2-aminoethyl)bis(2-pyridylmethyl)amine. After column chromatography using CHCl₃ : MeOH (9 : 1, v/v), compound 1 was obtained in a 42% yield. In the part D, N-bromoacetamide was used as the nitrogen source following a typical AA procedure for cinnamate ester to prepare the corresponding aminohydroxylation product from the vinyl phosphonate 1. However, in our initial attempt using 1.1equiv of N-bromoacetamide, no starting material 1 was consumed in the presence of different kinds of 1 : 1 aqueous solvents such as tert-butyl alcohol, 1-propanol, and acetonitrile and a prolonged reaction time (2 days), although the color of the reaction mixture changed from green to light yellow in all cases. Once 3.5 equiv of N-bromoacetamide was added, all of the starting vinyl phosphonate disappeared within 2 h and we observed an unexpected syn-β-amino-α-bromination product instead of aminohydroxylation product.