overhead projector demon~tra tion~ A Simple QualitativeTechnique for Pattern Recognition in Structure-Activity Relationships Glenn Roy The NuIrasweet Campany Mt. Prospect, IL 60056
The human sense of taste is affected by chemically specific stimuli interacting with proteins of discrete topology ( I ) . Pattern recognition of molecular shape aids in matching activity toa ~ ~ s s i b l e r e c e ~map,although tor ltai ( 2 )remarks that the coinridence of molecular shape is not always essential for bindine to the same receotor. Chemistry cexts provide no systematic procedures that involve students in the construction of these structure-activity relationships (SAR's). SAR has become a mainstay of oharmaceutical research since new and more effective drugs Hre often discovered by investigation of structure-activity relationships portrayed on sophisticated computers. I t would be cumbersome and expensive to expose students to SAR development using state-of-the-art computers. Outgoing Education Secretary Bennett has emphasized the need for stronger science in schools, but the curriculum outlines do not generally include the role of the computer. The knowledge and creative edge gained by understanding SAR is necessary for the scientists of tomorrow as new modes of effector-receptor function are revealed. This revelation can be effectively and innovatively demonstrated to a class by means of overhead projection.
edited by
DORISKOL8 Bradley University Peoria. IL 61625
For many years I have utilized a simple qualitative method to identify emerging patterns of likeness among large numbers of relativelv rieid structures. AORTA exercises (Acetate Overlay ~ e p e a t k gTopology Assay) provide an inexpensive way to introduce high school or college students to the ever-expanding library of structure-taste relationships without the need of a computer. A case in point involves the SAR of certain sweet- and hitter-tasting substances. The AORTA technique provides a ready rationale for the relationship of activity among such diverse structures of tastants as 1-7 (Figure 1). In addition to fostering fun and comorehension. this exercise insoires the creation of a receotor surface and an understanding of the principles of human taste biochemistrv. A steo-bv-sten AORTA exercise can be prepared from thestrud;res"incl;ded in Figure 1;the structures can be enlarged with a copy machine for better legibility. Procedure
Step 1. Photocopy the structure sheet, enlargingtofull size (two successive 154%enlargements will produce an appropriate master copy) onto an 8.5- X ll-in. 3M 688 or other suitable transparency film for overhead projection. Cut the structures individually with scissors. Using dry-erase markers, color code the functional groups (i.e., NH region as blue, C02H and S08Has red, and hydrocarbons as meen). . Step 2. Regin the exercise hy overlaying [he rommon colors of structure drawings. and verhally f d l w the ordrr of the pertinent information. On the overhead projuctor it is clear thnt n pattern ra emerging when viewed through "layers" of structures as seen in Figure 2. Step 3. After verbalizing the demonstration, elicit comments from your class regarding ionic forces and intramolecular hydrogen bonding on a receptor surface. ~
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~~
Perllnent Information I
2
ASPARTAME
N-AROYLASPARTAMIDE
CYSTEIC AMIDES
Sweeteners such as aspartame 1 obey the Shallenberger theory of AH-B binding (3) to the sweetness receptor (the AH region is blue and the B region is red as prepared in step 1above) and possess a Kier (4) hydrocarbon portion (green). On the basis of these observations the theory of the "AH-BX sweetness triangle" was developed. Tsuchiya (5) of the Japanese Ajinomoto Co. recognized that the addition of another Kier hydrocarbon portion to the AH (blue) region resulted in a new sweet substance 2. The combined structures lead one to overlap the structure of an old literature sweetener (6), suosan 3. When Tsuchiya (7) and his group
6
ISOCYSTEICAMIDES
7
OENATONIUM BENZOATE
Figure 1. Shuctures of tastanta
Figwe 2. '*Layersuof structures seen using an overhead projector. Volume 66
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further combined these coincidental observations they generated a hybrid structure 4, which was also a sweet tasting substance. The close resemblance of structures is quite evident in the AORTA view, which indicates an A H - 5 x 2 hypothesis (Fig. 2). The carhoxylic acid function (red) is extremely imoortant to sweet taste since analoeues (8)incorporatingall o i the above regions with a sulfonii acid (red) are bitter 5.6. A structure with the ahsence of an, acid is denatoniumbenzoate 7, the most bitter compound known (9). Llterature Clted 1. Dastali, F. R.; Pria. S. Science 1966, 154, m.Hiji, Y;Kobayashi; Sato. M. Comp. Biochem. Physiol. 1971,3%3.367.Hiji. Y. Nature 1975,256,427.Chem. Eng. New 1987. (Dec. 27). and references therein. 2. Kato, Y.: Itai, A,:litaka, Y. Tetrahedron 1987,43(221.5229.ConnoUy, M.QCPEBuII. 1981.1,75. 3. Shsllenbewr,R.S.;Ap.rep.,T.ENoture (London) 1967,216,480:J.Agrie.FoodChom. ,ma,.., ,, " 0 , .."" 4. Kier, L. B. J. Plumn. Sci. l372,61,1394.See Cijolo, M. R.; Lelj,F.;Tsnaedi, T.: Temu8si.P. A.;Tui, A. J. Med. Chem. 1983,26,1060. 5. Tsuehiya, T.,et sl. Ajinommo, Ca.,Jpn. Kokai TokkyoKohoJP 62,252,754. 6. Potemen, S.; M u l b , E. Cham. Eel. 1948,81.31. 7. Tsuchiya, T., at al. Chem. Abalr. 1063214377j to Ajinamato. Co.. Jpn. Kokai T O M Koho JP 61,260,052; Chom. Abstr 1073196772~to Ajinomoto Co., JP 62.132.847: Ghsm. Absfr. 108:75851k to Ajinomoto, Co.,JP 62,132,863. 8. RDse~~sereh Triangle Institute, Chemistry and Life Sciences Group, Life Seienaa and Tarimio~ Division. Final Repart of Contrad No. N01-DE-02428 submitted to the Offlee of Collaborative Research for T h e National Institute of Dental Research; compound RTI-2075-014 and RTI-2075-011. 9. The Merck Inder, An Encyclopedia of Chomicob, Dmg8, and Biologieab, 10th ed.: Rahwiay, NJ, 1983:p 417
A Microscale Study of Gaseous Diffusion Dlanne N. Epp East High Schwl 1000 So. 70th Lincoln, NE 68510 Edward J. Lyons East High Sehwl 1000 s . 7 m Lincoln, NE 68510 Davld W. Brooks Center for Science. MBthemti(a, and Computer Education University of Nebraska Lincoln. NE 68588 Demonstrations or experiments involving gaseous diffusion are limited in number1, perhaps due to the difficulty of handling and observing gases. The following microscale experiment compares qualitatively the rates of diffusion in air of chlorine molecules and ammonia molecules. I t may be projected conveniently on an overhead projector or carried out as a hands-on laboratory exercise. When working with a nonuniform mixture of gases, the gases diffuse into each other until a uniform composition is achieved. The classical work performed by Thomas Graham2 and since discussed by other^^,^ showed that, a t constant pressure and temperature, the rate of diffusion is inversely orooortional to the sauare root of the densitv of the gas. ~ o i amass r is often sibstituted for density. 1f 'the gasesare diffusinaintoair, amore general statement can be developed that relates the rate of diffusion to the concentration o f t h e gases. Procedure Prepare the cover of a 96-well flat-bottom plastic tissue culture plate by drilling small holes near two apposite earners of the cover (see figure). The experiment is carried out an a clear acetate sheet.
'
Shakhashiri,B. 2. ChemicalDemonstrations, Volume 2 University of Wisconsin: Madison. 1985: pp 55-74. 2(a)Graham,T. Phil. Mag. 1833,2:175,269; Graham, T. Phil. Mag. 1833, 2:175, 351; (reprinted in Graham. T. Chemical and Physical Researches; Edinburgh University, 1876; pp 44-70.) Mason. E. A,; Kronstadl. B. J. Chem. Educ. 1967,44.740. *Kirk, A. D. J. Chem. Educ. 1967, 44,745.
436
Journal of Chemical Education
I
grid on acetatesheet Dlthrsion apparatus.
Draw a 1-cmgrid the size of the cover onto the sheet. Use the reverse side of the acetate sheet to prevent interaction of the chemicals with the grid lines. Grid lines may conveniently he printed onto an acetate sheet using a suitable transparency maker. Leave 2 x 2 corner squares of the grid (to he located under the holes in the cover plate) empty. To each of the other squares in the grid, add 1drop of 0.1 M KIIphenolphthalein solution. (To 100 mL of 0.1 M KI add 2 mL 1%phenolphthalein salution.) Cover the grid with the prepared cover plate. Through one comer hole add 3 drops of bleach to the center of one corner square. Working quickly, simultaneously add 2 drops of 3 M HCI to the bleach through the cover hole shove the bleach and 3 drops of concentrated ammonia to the center of the emntv . . sauares . in the opposite corner of the grid. Cover both holes with small pieces of rape. Observe the colurchanges with time for several minutes. Wash the aL.emte sheet and plastic cover at a sink with large amounts of running water. Reactions and Conclusion Bleach contains chloride and hypochlorite ions. A strong acid will cause chlorine gas to be released from the solution: Cl
+ ClO- + 2Ht
t Clz
+ Hz0
The progress of the chlorine gas as it diffuses is observed by the formation of colored iodine molecules as the iodide ions a t the surface of the KI drops are oxidized:
+ =1%+ ZCI-
Cln 21-
The progress of the gaseous ammonia molecules is followed by the effect on ~henolohthaleinwhen the extremely soluble ammonia molecules &ssolve and form a basic sol;tion in the aqueous K I solution. By following the color changes in the Kllphenolphthalein solution, students observe several imoortant features of diffusion. First, although the gases are diffusing into air, which impedes their progress, the net movement of the gases is rather rapid. Second, i t is readily noted that the lighter ammonia molecules (17 glmol) diffuse more rapidly than do the heavier chlorine molecules (71 glmol).
Rotation of Polarized Light by Stereoisomers of Limonene Sally Solomon hexei University Phlladeiphla. PA 19104 Equipment and Chemicals overhead projector two 10-mLbeakers four squares of Polaroid HN film cut from a 15- X 15-em square' (R)-(+)-limonene;97902 (S)-(-)-limonene; 975S
Procedure Neat samdes of limonene stereoisomers are used to demonstrate the rotation of polarized light on anoverhead projector. I.imonene,a terpene occurring in orange and lemon oils, was chosen bemuse it is safe to handle and has stereoisomerr that are readily available and relatively inexpensive. The demonstration can be done on a transparency displaying the limonene formula, with a second transparency used as a n overlay to protect against spills. T o begin the demonstration one polaroid square is turned 90' and placed upon another sauare to show students that no lieht (or verv little lieht) can be seen cdming through the crossed polar;& T W O ~ O -heakersare m~ filled about rwo-thirdr full with the twolimoneneisomerswd then placed between two sets of crossed polarhers. The top polarbers are rotat-
ed (in opposite directions) to extinguish the light. An optically inactive sample such as water may be tested first. Appropriate amounts of the limonene samples can be stored conveniently in 20-mL screw-cap glass scintillation vials."ince the limonene eventually deteriorates, the samples should be tested before doing the demonstration.
' Fisher Scientific: catalog number 13-789A. Aldrich; catalog number 18, 316-4. Aldrich; catalog number 21, 836-7. Klmble: catalog number 74515.
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