Branched polyphosphates can be stable after all

Polyphosphates are found in living organisms in both linear and cyclic forms. They are thought to act as storage molecules and phosphate donors. Since the 1950s, researchers have thought that branched polyphosphates—also called ultraphosphates—are too unstable to survive in cells’ aqueous environments. But Henning J. Jessen of the University of Freiburg and his coworkers thought that ultraphosphates—especially ones without cyclic substructures—must also be present in cells. “If all these structures are known, ultraphosphates should also be there,” Jessen says.

Jessen and his colleagues couldn’t find ultraphosphates in biological systems, so they focused on the chemistry instead (Nat. Commun. 2021, DOI: 10.1038/s41467-021-25668-3). “We wanted to figure out what would be conditions we could see them at all. If you treat them the wrong way, they hydrolyze very quickly,” Jessen says. “We’re able to figure out under which conditions they are kind of stable, so we think there is a chance of identifying them in biology.”

The researchers synthesized the smallest possible ultraphosphate—a central phosphate surrounded by three others—by coupling organically modified phosphates with tris(diethylamino)phosphine followed by oxidation. Symmetrical ultraphosphates, ones with identical organic groups, are more stable than unsymmetrical or unmodified ultraphosphates. Depending on the organic groups, some ultraphosphates could survive hours or even days in water, much longer than had been thought possible. Other ultraphosphates hydrolyzed rapidly. Lower pH and the presence of some cations accelerated the decompositon.

The researchers found that the ultraphosphates undergo rearrangements to form linear polyphosphates, and their computations show that branched and linear polyphosphates have similar energies. This may help explain why branched polyphosphates have been so hard to find.

The work “demonstrates convincingly that branched polyphosphates can be stable in water—or unstable, depending on the exact makeup of the branched polyphosphate,” says James H. Morrissey, an expert on polyphosphates at the University of Michigan Medical School. “It will be very interesting to see if this class of polyphosphate occurs in nature.”

Ultraphosphates could potentially serve as phosphorylating reagents. Jessen and coworkers used an ultraphosphate as a phosphorylating agent under conditions mimicking those thought to prevail on prebiotic Earth. They were able to phosphorylate various molecules, including aliphatic amines, amino acids, and nucleosides. The reaction is not particularly efficient because it results in the transfer of one phosphate and the loss of the other three.

The next step for Jessen’s group is to make ultraphosphates with longer phosphate chains and multiple branching points. Jessen also hopes to identify enzymes that can make or use ultraphosphates.