Hand-in-glove

One of the more fascinating bits of biochemistry is the odd "handedness" (technically called chirality) that a lot of biological molecules have.  Chiral molecules come in a left-handed (sinistral) and a right-handed (dextral) form that are made of exactly the same parts but put together in such a way that they're mirror-images of each other, just like a left-handed and right-handed glove.

Where it gets really interesting is that although the left-handed and right-handed forms of biologically active molecules have nearly identical properties, they aren't equivalent in function within living cells.  Nearly all naturally-occurring sugars are right-handed (that's where the name dextrose comes from); amino acids, on the other hand, are all left-handed (which is why amino acid supplements often have an "l-" in front of the name -- l-glutamate, l-tryptophan, and so on).  Having evolved with this kind of specificity has the result that if you were fed a mirror-image diet -- left-handed glucose, for example, and proteins made of right-handed amino acids -- you wouldn't be able to tell anything apart by its smell or taste, but you would proceed to starve to death because your cells would not be able to metabolize molecules with the wrong chirality.

Chirality in amino acids [Image is in the Public Domain courtesy of NASA]

Molecular chirality was used to brilliant effect by the wonderful murder mystery author Dorothy Sayers in her novel The Documents in the Case.  In the story, a man dies after eating a serving of mushrooms he'd picked.  His friends and family are stunned; he'd been a wild mushroom enthusiast for decades, and the fatal mistake he apparently made -- including a deadly ivory funnel mushroom (Clitocybe dealbata) in with a pan full of other edible kinds -- was something they believed he never would have done.

The toxic substance in ivory funnels, the alkaloid muscarine, is -- like many organic compounds -- chiral.  Naturally-occurring muscarine is all left-handed.  However, when it's synthesized artificially in the lab, you end up with a mixture of right- and left-handed molecules, in about equal numbers.  So when the contention is made that the victim hadn't mistakenly included a poisonous mushroom in with the edible ones, but had been deliberately poisoned by someone who'd added the chemical to his food, the investigators realize this is the key to solving the riddle of the man's death.

Chiral molecules have another odd property; if you shine a beam of polarized light through a crystal, right-handed ones rotate the polarization angle of the beam clockwise, and left-handed ones counterclockwise.  So when an extract from the victim's digestive tract is analyzed, and a polarized light beam shined through it splits in two -- part of the beam rotated clockwise, the other part counterclockwise -- there's no doubt he was poisoned by synthetic (mixed-chiral) muscarine, not by mistakenly eating a poisonous mushroom that would only have contained the left-handed form.

So specific chirality is ubiquitous in the natural world.  We have a particular handedness, all the way down to the molecular level.  What's a little puzzling, however, is why this tendency occurs.  Not chirality per se; that merely arises from the fact that if you bond four different atoms or groups around a central carbon atom, there are two ways you can do it, and they result in molecules that are mirror images of each other (as shown in the image above).  But why do living things all exhibit a preference for a certain handedness?  It must have evolved extremely early, because virtually all living things share the same preferences.  But what got this bias started -- especially given that left-handed and right-handed molecules are equally easy to make abiotically, and have nearly identical physical and chemical properties?

Well, a paper this week in the journal Advanced Materials may have just answered this long-standing question.  A group led by Karl-Heinz Ernst, at the Swiss Federal Laboratories for Materials Science and Technology, found that the selection for a particular handedness happened because of the interplay between the electromagnetic fields of metallic surfaces with the spin configuration of chiral molecules.

They created surfaces coated with patches of a thin layer of a magnetic metal, such as iron or cobalt, and analyzed the magnetic "islands" to determine the direction of orientation of the magnetic field of each.  They then took a solution of a chiral molecule called helicene, which had equal numbers of right and left-handed forms, and poured it over the surface.  The hypothesis was that the opposite patterns of spin of the electrons in the two different forms of helicene would allow them to bond only to a magnetic patch with a specific orientation. 

So after introducing the mixed helicene to the metal surfaces, they looked to see where the molecules adhered.

Sure enough -- depending on the direction of the magnetic field, one or the other form of helicene stuck to the metal surface.  The magnetic field was acting as a selecting agent on the spin, picking out the handedness that was compatible with the orientation of the patch.

This, of course, is only a preliminary study of a single chiral molecule in a very artificial setting.  However, it does for the first time provide a mechanism by which selective chirality could have originated.  "In certain surface-catalyzed chemical reactions," Ernst explained, "such as those that could have taken place in the chemical 'primordial soup' on the early Earth, a certain combination of electric and magnetic fields could have led to a steady accumulation of one form or another of the various biomolecules -- and thus ultimately to the handedness of life."

So a simple experiment (simple to explain, not to perform!) has taken the first step toward settling a question that chemistry Nobel laureate Vladimir Prelog called "one of the first questions of molecular theology" back in 1975.  It shows that science has the capacity for reaching back and explaining the earliest origins of biochemistry -- and how life as we know it came about.

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