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value about 10,000 times that attainable in thegeomagnetic field, and transferred the samplewithin one second into the detection coil of anEarth-field NMR spectrometer. They investi-gated benzene, lithium chloride dissolved in water, tetramethylsilane, silicone oil, octa-methylcyclotetrasiloxane and nonafluoro-hexene, demonstrating in each case that theirspectrometer could image these compounds’molecular structure. The instrumental broad-ening of their spectrometer is only a few milli-hertz over a sample volume of 1 cm3 — lessthan the broadening of high-resolution NMRwith advanced superconducting magnets. The spectral resolution is, however, limited bythe shorter spin relaxation time to a few tenthsof a hertz.

The authors predict that the combination oflow-field NMR with advanced methods of spinhyperpolarization will allow time-resolvedNMR spectroscopy of rare nuclei such as 6Li,13C and 29Si, and the separation of the corre-sponding J-couplings with high precision.Many applications of this mobile low-fieldNMR technique are also likely in medicine andmaterials science: the tracking of hyperpolar-ized 6Li+ and 7Li+ migrating through ion channels or membranes, for example, or thecharacterization of mineral oil in well-loggingand the online detection of chemical reactions.

Earth-field NMR cannot replace the diag-nostic capabilities of the chemical shift measurements available with the high-fieldmethod. But particularly in combination with

their basic trade: the synthesis and characteri-zation of new molecular entities.

The authors propose three basic approachesto squeezing C–C bonds: caging, crowdingand clamping. They evaluate all three compu-tationally, using a reasonable computationallevel for the rough screening of structures.Such simulations represent a departure by

CHEMISTRY

Brevity for bonds Jay S. Siegel

Fashion design? Game-playing? Designing the shortest bond between two carbon atoms can seem to have elements of such apparently ephemeral pursuits. But it can also stretch the chemist’s creativity.

Carbon–carbon (C–C) bonds could be tail-ored shorter this coming season, according toDeborah Huntley and colleagues, who includethe Nobel laureate Roald Hoffmann. Theirpredictions appear in an unlikely fashion mag-azine, the journal Angewandte Chemie Inter-national Edition1. The authors highlightseveral ways to sport short bonds, but it will beno small task for manufacturers to bring thesedesigns into reality.

Molecular fashion has long been thechemist’s playground2 — no wonder, givenchemistry’s unique position in the design andsynthesis of new forms of matter. The pursuitof novel molecular structures has led chemiststo uncover material properties that cannot berevealed by observational science alone. Suchcreativity blends the hard science of chemistrywith the engineering and aesthetic compo-nents of architecture and sculpture — or evenhaute couture. A question that often stemsfrom a molecular-design hypothesis is “Canwe make that?”. Whether the answer is yes orno, addressing such questions in a scholarlymanner can generate great chemical insight.

In their paper, Huntley and colleagues1 askhow many ways a C–C bond can be squeezed,and what is the resultant degree of shortening.They cite precedent from Henning Hopf ’s1976 essay “Wie kurz kann eine Einfach-bindung werden? Wie stark lässt sie sichstauchen?” (“How short can a single bond be?How strongly can it be compressed?”)3. Assuch, their call for a renewed interest in shortbonds can be seen as a revivalist trend, whichcould signal a return to training chemists in

Bond length (r)00

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1.501.471.41 1.440

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Figure 1 | Bonding energy potential and carbon–carbon bond-length distribution. a, The C–C bond can be considered energetically as two balls joined by a spring. Pulling them apart becomesincreasingly harder (requires more energy) the longer the bond gets. Pushing them together will also become more difficult as they almost come into contact. But somewhere in the middle is a stable state. Although this approximation (the blue line) works fairly well, especially at the bottomof the energy well, a more realistic energy profile (grey line) is asymmetrical because the energy ofstretching the bond is limited by the bond dissociation energy. The energy of interaction decreases as the atoms move apart; the red line shows a qualitative expectation of the distribution observed for b.b, Distribution of observed bond lengths, compiled from data from the Cambridge StructuralDatabase5. Skew towards longer bonds becomes evident only past the 3� level of deviation beyond the ‘normal’ bond length of 1.53 Å.

superconducting quantum interference device(SQUID) detectors8, the technique could givelimited, but potentially very useful, informationabout the coupling of many molecules. ■

Janez Stepis̆nik is in the Physics Department,University of Ljubljana, Jadranska 19, 1000Ljubljana, Slovenia.e-mail: Janez.Stepisnik@fmf.uni-lj.si

1. Appelt, S., Kühn, H., Wolfgang, F. & Blümich, B. Nature Phys.2, 105–109 (2006).

2. Proctor, W. G. & Yu, F. C. Phys. Rev. 77, 717 (1950).3. Ramsey, N. F. & Purcell, E. M. Phys. Rev. 85, 143–144 (1952).4. Waters, G. S. & Francis, P. D. Sci. Instrum. 35, 88–93 (1958).5. Bene, G. J. Phys. Rep. 58, 213–267 (1980).6. Stepis̆nik, J., Erz̆en, V. & Kos, M. Magn. Reson. Med. 15,

386–391 (1990).7. Shushakov, O. A. Magn. Reson. Imaging 14, 959–960 (1996).8. McDermott, R. et al. Science 295, 2247–2249 (2002).

Hoffmann from his normally more poeticapproach to theory. But given the goal ofdesigning the shortest bond, one is left to grindout the numbers, or grind out the synthesisand structure determination.

In the end, investigating the concept of rela-tive molecular compressibility teaches us moreabout the behaviour of molecules than can thesize of the deviation from the ‘normal’ bondlength of 1.53 Å. Huntley et al. predict a worldrecord of 1.32 Å, but there is a chemistry lesson to be learnt from any compound that bears a C–C single bond less than 1.4 Ålong, for example.

The shape of the ‘potential-energy well’ forstretching a C–C bond — the curve showingthe relationship between the system’s potentialenergy and the distance between two carbonatoms — is asymmetric; distortions to longer

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distances cost less energetically than those toequivalently shorter ones. One might thereforethink that longer bonds would form far morereadily than shorter ones. Indeed, spectacu-larly long bonds of more than 1.7 Å have beenreported4. However, the potential energy isvirtually symmetric near the bottom of thepotential well, like the potential-energy well ofa simple ball-and-spring model of a molecule(Fig. 1a). Empirically (from 50,000 hitsobtained from the Cambridge StructuralDatabase5), observed C–C bond lengths aredistributed with no apparent skew towardslonger bonds well past the three-standard-deviation (3�) mark (bond length r�1.53 Å,��0.015 Å; Fig. 1b). This result is consistentwith Huntley and colleagues’ computation thata compression of 0.05 Å would ‘cost’ only 0.7 kJ per mol more than elongation. To achemist thinking of the distribution as beingequilibrated at room temperature, such anenergy difference would suggest a long-to-short ratio of 3:4 in the numbers of C–C bonds.

With such a wide range of ‘naturally’ occur-ring bonds, the design component becomes anovelty only at deviations beyond 6� (about0.1 Å), with especial interest focused on devi-ations of more than 10� (0.15 Å) — bondslonger than 1.7 Å or shorter than 1.4 Å. Atsuch extremes, the asymmetry of the poten-tial-energy well does play a substantial role inthe energetics, and this is also reflected in thebond-length distribution. In particular, exper-imentally sound C–C bond distances below1.4 Å are big news.

Coincidentally, Huntley et al. estimate thatthe hypothetical energy required to compressa C–C bond by 10% (0.15 Å) is roughly 10%(38 kJ per mol) of the bond energy, if directedalong the bonding axis. This energy require-ment would essentially preclude the naturalformation of structures with very short C–Cbonds, and would relegate such bonds to thenon-natural products pursued by those

engaged in chemical design and synthesis.How might one go about designing a short

C–C single bond? Let’s begin by recognizingthat an observed molecular structure is astructure in equilibrium, where the forces arebalanced and potential energy is minimized.Distortion of a ball-and-spring model of amolecule reveals that molecules respond tostresses by distributing the energy into a vari-ety of distortion modes, favouring thosemodes for which the forces can be balancedwith minimum increase in internal energy6.This is sometimes presented as a sort of struc-tural compensation principle, in whichstretching one bond correlates with shrinkinganother, or the widening of one angle corre-lates with the narrowing of another. Oneexample is that of octahedral distortions, inwhich the lengths of bonds to ligands in axialpositions correspond inversely to those in theequatorial plane.

To make a C–C bond shorter, one needs topush, clamp or tug the carbons together whileproviding a scaffolding that is sufficiently stiff. Distances between non-bonded atoms,dihedral angles and bond angles all provide‘softer’ distortion modes (that is, weakerspring potentials) than bond-length distor-tions to dissipate strain energy and weaken thecompression. The use of axial symmetry canhelp to focus the compression along the bond-ing axis. Thus, the three-fold symmetric cagespresented by Huntley and colleagues1 makegood design sense.

As a historical note, it should be remem-bered that the pursuit of molecules with com-pressed bonds started before the advent ofroutine X-ray and computational ab initioanalysis. Examples are hexaisopropylbenzene7,the ‘iron maidens’ (cyclophanes) of RobertPascal8,9 and intermediates en route to the‘bird-cage’ hydrocarbons10,11. All of these display large shifts in their carbon–hydrogeninfrared stretching modes, a sign that they

possess compressed carbon–hydrogen bonds.In the case of bird-cage hydrocarbons, thatbond length was found by neutron diffractionto be 1.078 Å, compared with the standardaverage length of 1.115 Å.

Coupled with chemical synthesis and struc-ture elucidation, molecular design has longbeen an engine of creativity in chemistry. Thenotion of squeezing C–C bonds may seempure game-playing, or a fashion that won’t lastbeyond the current season. But it is simply oneaspect of molecular design, and a myriad ofproblems involving extreme molecular geom-etries can be envisaged. For example, from theidea of a squeezed bond, one might try to cre-ate a molecular gauge in which the distortionsof a common scaffold would be translated to an energy of compression for a variety ofcompressed central bonds. In any case, theCambridge Structural Database5 is an invalu-able reference for what is ‘normal’: from there,designing the abnormal may lead to a deeperunderstanding of chemical structure. ■

Jay S. Siegel is at the Organic Chemistry Institute,University of Zurich, Winterthurerstrasse 190,8050 Zurich, Switzerland.e-mail: jss@oci.unizh.ch

1. Huntley, D. R., Markopoulos, G., Donovan, P. M., Scott, L. T.& Hoffmann, R. Angew. Chem. Int. Edn 44, 7549–7553(2005).

2. Nickon, A. & Silversmith, E. F. Organic Chemistry: The NameGame — Modern Coined Terms and their Origins (Pergamon,Oxford, 1987).

3. Hopf, H. Chem. Unserer Zeit 10, 114–120 (1976).4. Baldridge, K. K., Ogawa, Y. K., Siegel, J. S., Tanaka, K.

& Toda, F. J. Am. Chem. Soc. 120, 6167–6168 (1998).5. www.ccdc.cam.ac.uk6. Bürgi, H.-B. & Dunitz, J. D. (eds) Structure Correlation

Vols 1, 2 (Wiley-VCH, Weinheim, 1994). 7. Siegel, J., Gutierrez, A., Schweizer, W. B., Ermer, O. &

Mislow, K. J. Am. Chem. Soc. 108, 1569–1575 (1986).8. Pascal, R. A. Jr Eur. J. Org. Chem. 3763–3771 (2004). 9. Song, Q., Ho, D. M. & Pascal, R. A. Jr J. Am. Chem. Soc. 127,

11246–11247 (2005).10. Winstein, S., Carter, P., Anet, F. A. L. & Bourn, A. J. R.

J. Am. Chem. Soc. 87, 5247–5249 (1962). 11. Ermer, O., Mason, S. A., Anet, F. A. L. & Miura, S. S.

J. Am. Chem. Soc. 107, 2330–2334 (1985).

When food gets scarce, cannibalismis always an option. In times offamine, soil-dwelling Bacillus subtilisbacteria (pictured) shut down,forming tough spores that can lie dormant for years. But beforethat, they stock up on nutrients by releasing a toxin that kills off their neighbouring siblings and then feed off the remains of the dead cells. But how do the toxin-producing bugs shieldthemselves from the poison’s deadly effects? Craig Ellermeier et al. (Cell 124, 549–559; 2006)have unravelled the surprisingly

simple mechanism that protects thetoxin-producers.

When nutrients are in shortsupply, a protein called SpoOA isactivated to coordinate the cells’response. This regulator seems to becontrolled by a bistable genetic switchsuch that it is turned on in onlyabout half of the cells in a bacterialpopulation. The activated SpoOAtriggers manufacture of the toxin(SdpC) and an ‘immunity’ protein.

With some nifty genetics,Ellermeier et al. have identified the immunity protein and workedout how it is regulated. The key to

the process is the fact that theimmunity protein is also a signal-transduction protein thatcontrols its own synthesis. As toxin accumulates outside the cell, the immunity protein — which lies in the cell membrane — mops it up, preventing the cell from being killed.

At the same time, the toxin workswith the immunity protein to grabhold of a repressor protein in the celland tether it to the cell membrane.The repressor normally inhibits thegene that encodes the immunityprotein, but it cannot function whenbound to the membrane. So the cellkeeps pumping out more immunityprotein. When all the toxin ismopped up, free repressor starts to

accumulate, shutting down furthersynthesis of the immunity protein.Thus, the cell produces only as muchimmunity protein as it needs.Helen Dell

MICROBIOLOGY

Protection racket

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