Synthetic Molecular Motors Not Be So Hopeless a Task As It Would at First Anthony P

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effect’, could allow males with the same kin-recognition mechanism, particularly father to recognize one another, whether among species in which social learning is an they were reared together or apart, as often inadequate or misleading guide to related- occurs in species where males mate with ness. I many females. Paul W. Sherman is in the Department of I believe that this is the most likely ex- Neurobiology and Behavior, Cornell University, 100 YEARS AGO planation. However, confirmation requires Ithaca, New York 14853, USA. Many observers in different countries, identifying what heritable cues males use e-mail: [email protected] noticing the fact that malaria is most (for example, calls, plumage or odour), alter- 1. Höglund, J., Alatalo, R. V., Lundberg, A., Rintamäki, P. T. & prevalent at the most active period of ing them experimentally, and observing Lindell, J. Proc. R. Soc. Lond. B 266, 813–816 (1999). mosquito life, have attributed malaria to the 2. Petrie, M., Krupa, A. & Burke, T. Nature 401, 155–157 (1999). whether manipulated males indeed prefer 3. Höglund, J. & Alatalo, R. V. Leks (Princeton Univ. Press, 1995). agency of this insect. Dr. Patrick Manson, in similar but unrelated lek-partners. 4. Deutsch, J. C. Behav. Ecol. Sociobiol. 34, 451–459 (1994). 2 1894, first brought the subject forward in Petrie and colleagues’ results are impor- 5. Widemo, F. & Owens, I. P. F. Nature 373, 148–151 (1995). England … . Bignami and Bastianelli, who tant for several reasons. First, they (and 6. Watts, C. R. & Stokes, A. W. Sci. Am. 224, 112–118 (1971). had been trying unsuccessfully to infect a 1 7. Kokko, H. & Lindström, J. Proc. R. Soc. Lond. B 263, 919–923 Höglund et al. ) suggest that lek-joining in (1996). man by allowing mosquitoes to bite him, some species is best analysed by considering 8. McDonald, D. B. & Potts, W. K. Science 266, 1030–1032 (1994). attributing their want of success to the use inclusive fitness, not just male–male compe- 9. Petrie, M. Nature 371, 598–599 (1994). of the wrong kind of mosquito, and, acting tition. Second, although phenotype match- 10.Sherman, P. W., Reeve, H. K. & Pfennig, D. W. in Behavioural Ecology, 4th edn (eds Krebs, J. R. & Davies, N. B.) 69–96 on the observations of Grassi, tried again ing has been observed in many invertebrates (Blackwell, Oxford, 1997). 10 with some mosquitoes imported from the and vertebrates (most recently in chim- 11.Sherman, P. W. Ethol. Sociobiol. 12, 377–386 (1991). malarious district. This time they succeeded panzees13), this is the first report for a lekking 12.Dawkins, R. The Extended Phenotype (Freeman, San Francisco, in infecting the man with malaria of the species. Third, the likelihood of self-refer- 1982). 13.Parr, L. A. & deWaal, F. B. M. Nature 399, 647–648 same type that prevailed in the district from encing in peacocks should galvanize studies (1999). 10,11,14 which the mosquitoes came. … Whether the of this intriguing, yet controversial , 14.Alexander, R. D. Ethol. Sociobiol. 11, 241–303 (1990). Anopheles can be extirpated from a locality, and by what means, will be the problem for scientific workers resident abroad to settle; Nanotechnology fortunately they seem to be confined to small areas, so the suggestion of Ross to draw off the water from stagnant pools may Synthetic molecular motors not be so hopeless a task as it would at first Anthony P. Davis appear. From Nature 7 September 1899. he construction of miniature, ‘nano- switches or shuttles, and they have great 50 YEARS AGO scale’ machines is a goal of modern potential in, for example, molecular-scale For the woman, Dr. Turquet saw two Tscience and technology, inspired by information processing. However they are possibilities fraught with anxiety and Richard Feynman’s remark that “There’s not capable of the continuous, unidirection- frustration and therefore likely to add to the plenty of room at the bottom”1. Chemists, sum of aggression in society. One is her by the nature of their discipline, are already entry into an occupational life in which her at the bottom, manipulating the smallest hν opportunities compare unfavourably with a entities that have complex shapes (molec- Trans-cis interconversion under the influence of light man’s. If, on the other hand, she prefers the ules), and which can therefore be used as older domestic role with its exemption from engineering components. While engineers the need to compete on the male pattern, and physicists explore the top-down Station 1 Station 2 she then faces the anxiety of choosing and approach to nanoscale engineering through securing a husband, on whose adequacy her lithography and scanning probe micro- own social status will largely depend, and to scopy, chemists are well placed to pursue whom she will lose some of her individual the bottom-up strategy, whereby molecular identity. In either case the woman meets an -scale components are created using chemi- Stopper Stopper Rotaxane – a ring imprisoned on a string, atmosphere of masculine superiority which cal synthesis and then self-assembled into shuttling between two stations contrasts sharply with her childhood devices by pre-programmed intermolecular experience of the mother’s seeming forces2. superiority in the home. Aggression results Among the more interesting challenges from the inferiority which she feels in such in this area is the design and synthesis of an atmosphere. “Hence,” said Dr. Turquet, ‘molecular actuators’, molecules that can “ambivalent feelings towards motherhood, undergo changes in shape in response to Catenane – a ring imprisoned on another ring, the declining birthrate, and an unconscious external stimuli and thereby, in principle, again moving between two stations desire to reject the more fundamental perform mechanical work. To date, most aspects of the feminine role”. research has concentrated on two-state Figure 1 Two-state molecular systems. From Nature 10 September 1949. systems, ranging from classical cis–trans Established molecular actuators include systems isomerism to more elaborate ‘rotaxanes’ and capable of cis–trans isomerism, where groups lie Many more extracts like these can be found in ‘catenanes’ (Fig. 1)3,4, and biomolecular con- on the same (cis) or opposite (trans) sides of a A Bedside Nature: Genius and Eccentricity in structs, such as a device based on the transi- double bond, and more complex strucures such Science, 1869–1953, a 266-page book edited by tion of right-handed to left-handed DNA5. as rotaxanes and catenanes. The rings in the Walter Gratzer. Contact Lisa O’Rourke. These systems, in which movement is driven rotaxanes and catenanes may be driven between e-mail: [email protected] by chemical, electrochemical or photochem- stations by chemical, electrochemical or ical forces, are best described as molecular photochemical input.

120 © 1999 Macmillan Magazines Ltd NATURE | VOL 401 | 9 SEPTEMBER 1999 | www.nature.com news and views al motion we would expect of a true molecular motor. Now, on pages 150 and 152 of a b this issue, Kelly et al.6 and Koumura et al.7 From molecular ratchet... trans-1 cis-1 report two different routes towards this Spindle seductive goal. Spokes hν The design of Kelly et al.6 is based on a previous attempt to construct a ‘molecular Brake ratchet’. In this earlier work, the rotation of ... to molecular motor a three-pronged ‘wheel’ was hindered by a curved ‘brake’ (Fig. 2a), whose asymmetrical Irreversible, thermally- shape was intended to favour rotation in one driven rotations particular direction8. Such unidirectional motion, driven only by ambient thermal energy, would have violated the second 1 2 9 cis-2 law of thermodynamics , and unsurprisingly trans-2 failed to occur. Careful NMR measurements showed that the ratchet rotated in either hν direction with equal probability. Kelly et al. have now modified their system, using the asymmetry of their brake to 3 produce chemically driven (and therefore thermodynamically allowed) motion in one Figure 2 Unidirectional motion produced by nanoscale rotors. a, In the chemically driven system direction. Functional groups are attached to created by Kelly et al.6, the ratchet design (top) is modified so that a link can be made between the the brake and one spoke of the wheel, allow- brake and one of the spokes. Making the link (1 ¡ 2) pulls the rotor into a strained, high-energy ing the two to be linked covalently. The link- position. Thermal energy is now sufficient to carry the spoke past the brake, allowing the rotor to age pulls the molecule into a strained con- regain its favoured situation as in 3. Cleavage of the link restores the original position, except that formation, so that it becomes energetically the rotor has moved through 120°. b, The light-powered system created by Koumura et al.7, viewed favourable for the spoke to slip under the down the axis of a central carbon–carbon double bond that links two identical halves of an alkene brake. Cleavage of the linkage returns the molecule. The double bond is trying to establish a planar structure — that is, to make the two halves system to its original chemical state, but with line up. But they are prevented from doing so by bulky substituent groups, resulting in a twisted the wheel having undergone one-third of a geometry with four distinct states. The barrier between cis and trans forms is high, but may be rotation. The system is not a true molecular overcome by ultraviolet irradiation. Asymmetric substituents (triangles) cause energy differences motor, as no provision is made for further between the two cis and two trans isomers, such that cis-2 is more stable than cis-1, whereas trans-1 movement, but it does demonstrate a is more stable than trans-2. At appropriate temperatures, the thermally driven cis-1 ¡ cis-2 and method by which chemical energy may be trans-2 ¡ trans-1 conversions take place irreversibly. The net result is continuous rotation in the transduced, on a molecular scale, into uni- presence of ultraviolet light. directional rotary motion. Understanding this and similar processes may be relevant the less stable isomer of each pair is followed required over four years to construct. It to natural molecular motors, such as ATP by thermal decay into the more stable iso- should not be forgotten, though, that syn- synthase10,11, which are also powered by mer, resulting in overall rotation (Fig. 2b). thesis is a massively parallel manufacturing chemical reactions. The authors have followed this cycle step- process; each mole of product corresponds A critical aspect of the above system is wise by performing the photochemical con- to ኈ6 ǂ 1023 discrete ‘nanodevices’. Both its chirality (handedness), without which a versions at low temperatures, which slows groups have probably made at least 1019 direction of rotation could not be defined, let the trans–trans and cis–cis interconversions units of their respective systems, and could alone pursued. The design of Koumura et al.7 so that each of the four species can be scale up by several orders of magnitude also obeys this principle. Their system is an observed in sequence. However, at higher if required. The bottom-up approach is alkene molecule (that is, it contains a car- temperatures there seems no reason why certainly challenging, but may ultimately bon–carbon double bond), and uses the the system should not rotate continuously have economics on its side. I photochemical cis–trans interconversion under ultraviolet irradiation, and so be Anthony P. Davis is in the Department of illustrated in Fig. 1. But whereas simple seen as a genuine, light-powered molecular Chemistry, Trinity College, Dublin 2, Ireland. alkenes are planar and achiral (that is, super- motor. e-mail: [email protected] imposable on their mirror images), the sys- Many problems remain before the prin- 1. Feynman, R. Eng. Sci. 23, 22 (1960). tem of Koumura et al. has a complex struc- ciples embodied in these molecular motors 2. Philp, D. & Stoddart, J. F. Angew. Chem. Int. Edn Engl. 35, 1155–1196 (1996). ture which prevents planarity, introduces can be incorporated in real, useful 3. Balzani, V., Gomez-Lopez, M. & Stoddart, J. F. Acc. Chem. Res. chirality and results in four distinguishable machines. The rotors must be coupled to 31, 405–414 (1998). states, two trans and two cis (Fig. 2b). As their surroundings, and the self-assembly 4. Sauvage, J. P. Acc. Chem. Res. 31, 611–619 (1998). expected, both trans–cis interconversions processes needed for nanoscale construc- 5. Mao, C. D., Sun, W. Q., Shen, Z. Y. & Seeman, N. C. Nature 397, 144–146 (1999). can be achieved by illumination with ultravi- tion still need to be worked out. Nonethe- 6. Kelly, T. R., De Silva, H. & Silva, R. A. Nature 401, 150–152 olet light of an appropriate wavelength. less, the results of these two groups provide (1999). The singular feature of this system is that, further confirmation that molecular-scale 7. Koumura, N., Zijlstra, R. W., van Delden, R. A., Harada, N. & for subtle structural reasons, one of each engineering is slowly edging towards reality. Feringa, B. L. Nature 401, 152–155 (1999). 8. Kelly, T. R., Tellitu, I. & Sestelo, J. P. Angew. Chem. Int. Edn Engl. pair of trans- and cis-isomers is more stable The difficulties should not be underestimat- 36, 1866–1868 (1997). than the other. Provided the temperature is ed; molecular design is still an uncertain 9. Davis, A. P. Angew. Chem. Int. Edn Engl. 37, 909–910 high enough to overcome the activation bar- business, and chemical synthesis can be (1998). 10.Noji, H., Yasuda, R., Yoshida, M. & Kinosita, K. Nature 386, rier between the two trans or cis isomers, the lengthy and painstaking. Indeed, an engi- 299–302 (1997). more stable of the pair is formed irreversibly neer may be amazed that the ‘partial motor’ 11.Walker, J. E. Angew. Chem. Int. Edn Engl. 37, 2309–2319 from its partner. So, light-driven creation of of Kelly et al., containing only 78 atoms, (1998).