Study on the Supramolecular Mechanism of the 2Cyclodextrin/ Nabumetone/ Linear Alcohol System and Its Analytical Application

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1 , ACTA CHIMICA SINICA Vol 60, 2002 No 10, / / Ξ, a a b Ξ ( a ) ( b ) 2 ( 2CD) (NAB), (ROH), 2CD 1/ 1 K app 2CD, 2CD/ NAB/ ROH 2CD,, 2CD 2CD,, g ml - 1, 1 05 ng ml - 1, 2,,, Study on the Supramolecular Mechanism of the 2Cyclodextrin/ Nabumetone/ Linear Alcohol System and Its Analytical Application TANG, Bo Ξ, a MA, Li a CHU, Chun b ( a Department of Chemistry, Shandong Normal University, Jinan ) ( b Shandong Jintai Medicine Scientific & Technological Co, Ltd, Jinan ) Abstract Nabumetone (NAB) forms a 1/ 1 supramolecular complex with 2cyclodextrin ( 2CD) both in the absence and presence of linear alcohols ( ROH) The apparent association constants, K app, were measured using a steady2state fluorescence method K app decreases linearly with an increasing number of carbon atoms in the chain of the alcohol We attribute this to a competition between nabumetone and linear alcohol for the 2CD hydrophobic cavity as detailed analysis of K app as a function of [alcohol ] suggests that the interactions in the 2 CD/NAB/ ROH system do not result in the formation of ternary supramolecular complex Quenching the florescence of nabumetone with NaI shows that the 2CD cavity acts as a shield against contact between nabumetone and this aqueous phase quencher, while addition of alcohols inhibits this protective effect This again suggests that alcohols occupy the space within the 2CD cavity and force nabumetone molecules to reside in the aqueous environment Based on the significant enhancement of the fluorescence intensity of nabumetone produced through complex formation, a spectrofluorimetric method for the determination of nabumetone in bulk aqueous solution in the presence of 2CD is developed The linear relationship between the fluorescence intensity and nabumetone concentration was obtained in the range of g ml - 1, with a correlation Ξ E2mail : edu com Received January 22, 2002 ; revised April 2, 2002 ; accepted June 17, 2002 (No ) (No Z2000B03)

2 No 10 : 2 / / 1835 coefficient ( r) of The detection limit is 1 0 ng ml - 1 There is no interference from the excipients normally used in tablet formulations The application of the present method to the determination of nabumetone in tablets gave satisfactory results and was compared with the reference method Keywords 2cyclodextrin, nabumetone, linear alcohol, supramolecular mechanism, spectrofluorimetric study, 42( )2, 2CD 22 ( 1),,, 2CD, [1 ],, [2 5 ] [6 ] [7 ] [8 - ] [9 ],1,, 1 1, g PE25 ( Perkin2Elmer ), ml - 1[2 5 ], 5 nm ;UV (Shimadzu ) ; phs23c ( ) ( 1 Scheme 1 Structure of NAB,99 8 %) :,0 5 mg ml - 1, 4, 2CD ( ) :,60, mol L - 1 NaI,2 0 mol L - 1, (0 25 g/ ) (0 50 g/ ) D2 1 4,, 1 2 6, 7, 8 2, 2 2CD :, (10 L, 0 5 mg ml - 1 ) 10 ml, 0 5 g ml - 1, 2CD, ( mol L - 1 ), 1 cm, ex / em = 267, nm/ 355 nm,, 2CD 2CD/ NAB,, 1 % ( V/ V), 0 1 ml 10 ml 2CD,, : 0 5 g K app, 2CD ml - 1, 2CD 0, , , 2CD/ mol L - 1, NaI NAB K app,,, 267 nm/ 355 nm, :

3 1836 Vol 60, 2002, mol, L - 1 2CD,, 267 nm/ 355 nm, 1 ;,, : 10, mg( mg),, 100 ml 20 L 10 ml,, [ (20 1) ] , 2CD, 2CD 2 2CD : 2CD nm 2 nm, ; nm 2 (A) 2CD ( mol L - 1, B) 1 nm, (20 0 g ml - 1 ) Figure 2 Absorption spectra of NAB (20 0 g ml - 1 ) in the absence (A) and presence of 2CD ( mol L - 1, B) 1 2CD 2CD, c 2CD : 0, , , , , mol L - 1 c NAB = 0 5 g ml - 1, ex = 267 nm Figure 1 Fluorescence emission spectra of NAB and NAB with different concentrations of 2CD From bottom to top c 2CD : 0, , , , , mol L - 1 c NAB = 0 5 g ml - 1, ex = 267 nm 2B 2CD, 2CD, 2CD/ NAB, 3, 2CD ( ) 2CD/ NAB, 2CD, 2CD, 2CD, /, /,,, ;

4 No 10 : 2 / / CD K 1 = [ 2CD/ NAB ], [NAB ][ 2CD] 2CD,, 3 2CD/ NAB c NAB = 0 5 g ml - 1, c 2CD = mol L - 1, = 1 % ( V/ V), ex = 267 nm (a), (b), (c), (d), (e) Figure 3 Fluorescence spectra of 0 5 g ml - 1 NAB in aqueous solution containing mol L - 1 2CD in the presence of various linear alcohol (1 %, V/ V) (a) no alcohol, ( b) ethanol, ( c) 12propanol, ( d) 12butanol, ( e) 12 pentanol ex = 267 nm : 2CD ; 0, ;[NAB ] g ml - 1 K app K 1 4 ( 20 2CD 38 8), 2CD,, 1 2 ( , 1/ 1 L 10 ml ),, 0 1 % ( V/ V),, 2CD NAB 1/ 1 ph 2 3 r CD/ NAB 1/ 1, a : NAB + 2CD 2CD/ NAB (1) : K 2, K 3 : ROH + 2CD ROH + 2CD/ NAB (2) 2CD/ ROH (3) 2CD/ NAB/ ROH (4), 2CD, [10,11 (1), (3) (4), ] : NAB + 2CD + ROH NAB complexed (5) NAB complexed 2CD/ NAB 2CD/ NAB/ ROH 2CD, K app : K[ ROH] = K app = [NAB ] bound [NAB ][ 2CD] Benesi2 [12 Hildebrand K ] app : (6) [NAB ] 0 [ 2CD] 0 I = K app (7) 1 + K app [ 2CD] 0 I [ 2CD ] 0 2CD ; 1 2CD/ NAB K 2 2 ph app Table 1 K, app for the complex between 2CD and NAB in the presence of various linear alcohol ph 2CD/ NAB a, K app / (10 2 L mol - 1 ) = 1 % ( V/ V) 1, K app,

5 1838 Vol 60, CD (7), c NAB = 0 5 g ml - 1, concentration ex / em = 267 nm/ 355 nm Figure 4 Change of the fluorescence intensity of NAB with addition of 2CD The solid line corresponds to the nonlinear regression fit of the experimental data to Eq 7 c NAB = 0 5 g ml - 1, ex / em = 267 nm/ 355 nm [10 ] : K 1 K app = 1 + K 2 [ ROH] (8), (9), K 1 2CD/ NAB, 4 ; Eqs (8) and (9) (9) 5 K app Figure 5 Variation of K app values as a function of 12pentanol K 1, K 2 [13 ] 2CD (63 L mol - 1 ) K 3, Bohne Evans [10,11 ] 2CD/ NAB/ ROH, : 2CD 2CD, NAB, ROH ; 2CD, NAB ROH, K app 2CD/ NAB, 2CD K app ( 5) 1 1 (1), (3) (4), K app [14 ] 2CD [11 ], 2CD : [10,11 ] K app = K 1 + K 2 K 3 [ ROH], (8) 1 + K 2 [ ROH] 2CD K app, (8) 2CD/ NAB/ ROH 2CD/ 22 / (4), [10 ], 4 H [15 ] 2CD/ NAB 2CD/ ROH, K app [16 ], K 1, K 2 2 (8), (9) 5 2CD/ NAB/ Table 2 Equilibrium constants for the 2CD/ NAB/ 12pentanol system calculated by fitting the data of Figure 5 by the model of, K 1/ K 2 / K 3 / (8), (9) 5, (L mol - 1 ) (L mol - 1 ) (L mol - 1 ) r 2 2, K

6 No 10 : 2 / / , 2CD/ NAB 2CD/ 22 / [10 ] 2CD/ / [16 ], K app, : 3, 2CD NaI 2CD,, 0 93, 3 72, : 2CD L mol - 1 [13 ], 2CD, K app, NaI :, 2CD 2 5, K app 2CD, 2 4 : F = c ( g ml - 1 ) + 2CD/ NAB , g ml - 1,, [17 ] NaI 2CD 0 092, IUPAC, [18 ], NaI, 90 % 1 05 ng ml - 1, 2CD 0 6 g ml Stern2Volmer 2 6 : F 0 / F = 1 + K sv [Q ] F 0 / F [Q],,0 6 g ml - 1, K sv 3, 3 K 1 5 %, K app 4 4, 3,, 2CD [NAB ] complexed / [NAB ] free K sv, : 2CD,, [NAB ] complexed / [NAB ] free, K sv 2 7 2CD NaI [10 ] [16 ], 2CD, [2 ], ( 5) 95 %,Cochran [19 ] : 2CD, 0 47 %, % %( 6) 3 NaI Stern2Volmer K sv ([NAB ] complexed / [NAB ] free ) a Table 3 K sv for the quenching of NAB fluorescence by NaI under various conditions and the concentration ratios of complexed NAB to free NAB [ 2CD]/ (10 mmol L - 1 ) K sv / (L mol - 1 ) [NAB ] complexed / [NAB ] free b K sv / (L mol - 1 ) 1 % [NAB ] complexed / [NAB ] free b a ex / em = 267 nm/ 355 nm, = 1 % ( V/ V) ; b 1 K app (6)

7 1840 Vol 60, g ml - 1 Nishida, M J Pharm Biomed Anal 2000, 23, 917 Table 4 Influence of excipients normally used in the tablet on the determination of 0 6 g ml - 1 NAB ( ) 3000,,, 4000,,,,,,, De, K J ; Vickery, W E ; Diamond, F X J Am 5 Soc Mass Spectrom 1998, 9, 255 Table 5 Determination of NAB in tablets [2 ] Chinese) / / (mg - 1 ) (mg - 1 ( ) / (mg - 1,, 1990, 25, 350 ) ) 10 Van Stam, J ; De Feyter, S ; De Schryver, F C ; Evans, a C H J Phys Chem 1996, 100, b Yuan, L ; Cornelia, B J Phys Chem 1996, 100, 734 a ; b 12 Barra, M ; Bohne, C ; Scaiano, J C J Am Chem Soc 1990, 112, Hami, S J Phys Chem 1989, 93, 2074 Table 6 Results for the recoveries of NAB from tablets 14 Elliott, N B ; Ndou, T T ; Warner, I M J Inclusion References 1 Boyle, E A ; Freeman, P C ; Mangan, F R J Pharm Pharmacol 1982, 34, Mikami, E ; Goto, T ; Ohno, T ; Matsumoto, H ; 3 Haque, A ; Stewart, J T Biomed Chromatogr 1999, 13, 51 4 Al2Momani, I F Anal Lett 1997, 30, Edward, R J ; Osborne, D R J Chromatogr 1984, 336, Li, P ; Ning, Y2J Chin J Pharm Anal 1993, 13, 96 (in Chinese) (,,, 1993, 13, 96 ) 7 Escuder2Gilabert, L ; Sagrado, S ; Villanueva2Camanas, R M ; Medina2Hernandez, M J J Chromatogr, B : Biomed Sci Appl 2000, 740, 59 9 Liu, M2L Chin J Pharm 1990, 25, 350 ( in / / ( g ml - 1 ) ( g ml - 1 ) ( g ml - 1 ) Phenom Mol Recognit Chem 1993, 16, Milewski, M ; Augustyniak, W ; Maciejewski, A J Phys Chem A 1998, 102, Bao Ha Au, M P ; Evans, C H J Photochem Photobiol, A 2001, 140, Murov, S L ; Carmicheal, I ; Hug, G L Handbook of Photochemistry, 2nd ed, Marcel Dekker, New York, Rohrbach, R P ; Rodriguez, L J ; Eryring, E M ; Wojeik, J F J Phys Chem 1977, 81, Zheng, Y2X The Method of Mathematical Statistics in Analytical Chemistry, Science Press, Beijing, 1986, p 122, 231, 308 (in Chinese) (,,,, 1986, p 122, 231, 308 ) (A LI, L T ; FAN, Y Y )

8 October 2002 Graphical Abstract 5 Studies on Zeolite Synthesis by Self2 transformation of B2containing Porous Glass in a Vapor Phase Solid2state Surface Reaction DONG, Wei2Yang ; REN, Yu ; ZHOU, Wei2 Zheng ; LONG, Ying2Cai Acta Chimica Sinica 2002, 60 (10), 1817 Study of Ethanol Sensitizing Effect on the Interaction of Titan Yellow and Proteins by Resonance Light Scattering Technology and Its Analytical Application WU, Hui2Ling ; LI, Wen2You ; HE, Xi2Wen Acta Chimica Sinica 2002, 60 (10), 1822 A new method for determination of proteins based on the sensitizing effect of ethanol on the interaction of titan yellow with proteins has been proposed A New Method for Surface Modification of Paraffin Impregnated Graphite Electrode for DNA Immobilization and Hybridization ZHENG, Sai2Jing ; LIN, Xiang2Qin ; YIN, Yi2Mei Acta Chimica Sinica 2002, 60 (10), 1828 The modification of CT2DNA and 152mer ss2dna onto the micro2hollow paraffin graphite impregnated electrode (MHPIGE) has been investigated using Co2 (phen) as an indicator The mechanism of DNA immobiliza2 tion by three2dimensional structure of been proposed micro2hollow has Study on the Supramolecular Mechanism of the 2Cyclodextrin/ Nabumetone/ Linear Alco2 hol System and Its Analytical Application TANG, Bo ; MA, Li ; CHU, Chun Acta Chimica Sinica 2002, 60 (10), 1834 A dramatic increase in fluorescence intensity is observed when 2CD is added to the aqueous solution of nabumetone and the fluorescence signals are intensified with increasing concentration of 2CD, which may be indicative of complex formation between 2CD and nabumetone