Science
Microwave circular dichroism seen feasible A small group of chemists has targeted microwave circular dichro ism (MW-CD) as the next frontier in molecular spectroscopy. Not yet The thermodynamic cycle-perturbation even attempted, MW-CD would be method is based on substituting for the differential absorption by asym theoretical processes of interest other metric molecules of right- vs. leftprocesses that are equivalent thermocircularly polarized microwave ra dynamically but whose thermodynam diation. If detected, MW-CD might ic properties are easier to estimate. yield molecular electric quadrupole For example, if the problem is to de moments, which in turn would re termine which of two substrates, Si or veal electron distributions in mole S2, will bind more strongly to enzyme cules to be checked against quan E, a thermodynamic cycle for free en tum mechanical calculations. ergy can be constructed: Compounds absorb microwave ra diation by transitions among rota AGi tional energy states, in which whole E + S molecules rotate about imaginary axes. Microwave spectroscopists an AG ΔΘ4 alyze molecular rotations in terms of spherical, symmetric, and asym metric tops, plus subtle variations of these. Spherical tops are com The thermodynamic quantity that de pletely symmetrical molecules, such termines which substrate binds more as methane. Methyl chloride is an tightly is the difference in free energy example of a symmetric top with changes for the two binding reactions: one axis of symmetry. Asymmetric AG2 — ΔΘν However, because all the tops have no axes of symmetry. free energy changes are part of a For now though, chemists must cycle, that value is equivalent to content themselves with theoreti AG4 — AG3. The chemical reactions cal calculations of the MW-CD ef that correspond to free energy changes fect and scan catalogs for the hard AG3 and AG4 are hypothetical ones; ware needed to see it. For example, they would not be expected to occur physical chemistry professor Prasad in an experiment. L. Polavarapu of Vanderbilt Uni versity presented his calculations to active site would affect its ability to the Molecular Spectroscopy Sympo bind to a particular inhibitor. In sium, held recently in Columbus, both cases, their calculated free en Ohio. ergy difference for the binding re Polavarapu uses classical physics actions agrees closely with values to predict that MW-CD is feasible determined by experiment. for compounds whose molecules are The researchers are just beginning chiral asymmetric tops. He has cal to tap the potential applications of culated that the dissymmetry factor their approach, McCammon says. ΔΑ/Α will be 10 - 5 to 10 - 6 , where Wong, for example, is testing its ΔΑ is the difference in absorption usefulness to enzyme engineering between right- and left-circularly by using it to try to design a better polarized microwave radiation, and trypsin enzyme. Another laborato A is the total absorption at a rota ry project is to predict the best de tional transition. sign for a crown ether to maximize The Vanderbilt chemist cautions binding to specific alkali metals in that his classical calculations do not methanol solutions. Another effort include effects of electronic charge looks at the interaction of promis flows during rotational transitions. ing antiviral drug candidates with They also do not predict the micro influenza virus. Still another thrust wave energies where spectroscopists is in fundamental theoretical de should look for optically active tran velopment intended to extend the sitions. But Polavarapu concludes range and power of the technique. that such dissymmetry factors are Rebecca Rawls, Washington within reach of currently available
Thermodynamic cycles key to Houston group's method
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June 30, 1986 C&EN
detectors. He suggests that his work might inspire others to do the quan tum mechanical calculations that will tell experimentalists what to look for and how to interpret what they see. The possibility of MW-CD was first shown by chemical physics pro fessor William R. Salzman at the University of Arizona [/. Chem. Phys., 67, 291 (1977)]. Salzman devised a semiempirical quantum mechanical method to predict the effect in an imaginary chiral spherical top. Physical chemistry professor Lau rence D. Barron of the University of Glasgow carried the work fur ther by calculating the effect for chiral symmetrical tops [/. Raman Spectr., 16, 208 (1985)]. Barron used quantum mechanics from first prin ciples for the example of triphenylboron, whose chirality came from the pitch of its phenyl "propeller blades/ 7 In practice, it would be im possible to resolve chiral conform e r of triphenylboron. Barron has gone on to develop a quantum mechanical method to cal culate rotational optical activity for the chiral asymmetric top molecules that may show the effect experi mentally. His graduate student, Caroline J. Johnston, has incorpo rated his method into a computer program. In the next few weeks, they expect to calculate rotational optical activity for such compounds as propylene oxide, 2,3-epoxybutane, and bromochlorofluoromethane. Experimentally, Barron will try to observe rotational Raman optical activity rather than microwave cir cular dichroism. In such an experi ment, one may see a difference in intensity between scattered rightand left-circularly polarized visible light. The difficulty is that he will be trying to detect differences in intensity of 10~5 in scattered light that is only 10 to 150 c m - 1 different in frequency from the excitation light. Also, because the molecules are so large, Barron does not expect to resolve individual optically ac tive rotational transitions but to see only broad, featureless bands. The payoff for success in Barron's experiment is the determination for the first time of some of the compo-
nents of the optical activity tensors. One of those is the magnetic dipole optical activity tensor, G. Another is the electric quadrupole optical activity tensor, A. Each of them has nine components according to spatial orientation. Knowledge of those components and their arithmetical differences would give chemists a harder grip than they have ever had on what makes a dissymmetric molecule optically active. Generation of the circularly polarized light needed to carry out the experiment is already routine for microwave-based communications. Plane-polarized microwave sources and devices to induce circular polarization are sold by such firms as Millitech Corp., South Deerfield, Mass. In a first step, planepolarized microwave radiation is generated by a Gunn diode. A Gunn diode is a gallium arsenide device whose semiconductor components are doped in a sequence that causes a bunching of electrons as an electric field is applied across it. The
bunches of electrons tunnel through the junctions of semiconductor components dozens of billions of times per second, producing microwave radiation of the order of dozens of gigaHertz. The planar propagation of the electric vector of the polarized microwave radiation that comes from such a highly ordered device can be thought of as a combination of two electric vectors rotating in opposite directions. When the two counterrotating vectors meet at 12 o'clock, they reinforce one another, and the wave reaches a crest. When they meet at 6 o'clock, they reinforce one another again, and the wave reaches a trough. Placing a sapphire crystal in front of the source retards one of the counterrotating vectors 45°. That's because the sapphire has different indexes of refraction in different directions. The retardation causes the whole combination of electric vectors to rotate, producing circularly polarized radiation. Rotating the
sapphire 90° allows alternation between left- and right-circularly polarized radiation. Alternatively, chemists might achieve circular polarization with quasi-optical devices. Those are assemblies of wire grids and parabolic mirrors that similarly retard one rotating electric vector. To detect such minute differences in absorption of right- and leftcircularly polarized microwave radiation, chemists may make use of the Stark effect. The Stark effect is the change in frequency of microwave radiation absorbed during a rotational transition caused by an electric field applied perpendicular to the direction of the radiation beam. By turning the electric field on and off at a certain frequency and setting an amplifier to pass only microwave radiation modulated at that frequency, chemists can screen out background or stray microwave radiation and improve the signal-to-noise ratio of the spectrometer. D
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