Protomatter was a highly dangerous, unstable form of matter.
Its hazardous properties led to its denunciation by most 23rd century scientists, but this did not stop David Marcus from secretly using it while trying to solve certain fundamental problems inherent in the Project Genesis matrix. By doing so, he inadvertently doomed the project to failure as it caused the planet formed by the matrix to inherit the unstable properties of the protomatter. (Star Trek III: The Search for Spock)
In 2374, the USS Voyager encountered a class 1 nebula that contained high concentrations of protomatter. Neelix, who had worked with protomatter in the past, was killed while protomatter was transported into a canister he was holding. Seven of Nine subsequently brought him back to life with her Borg nanoprobes. B'Elanna Torres speculated that a phase variance in the transporter beam was responsible for igniting the sample of protomatter that Neelix had attempted to collect. (VOY: "Mortal Coil")
In the novel Foul Deeds Will Rise, Captain James T. Kirk and the crew of the Enterprise-A participate in crucial disarmament talks for two planets, with some of the natives attempting to finish the war by stealing one of the protomatter warheads that are being destroyed as part of the peace process and launching the warhead at a major city on the other planet, but these efforts are thwarted thanks to the actions of Spock, Montgomery Scott, and the redeemed Lenore Karidian.
In the The Genesis Wave trilogy, Captain Jean-Luc Picard reads a summary of the Genesis project that includes the observation that the instability of the Genesis planet was caused due to it being created from the remains of the Mutara Nebula rather than the protomatter being the problem in itself, speculating that the Genesis effect would have been successful if it had been used on a lifeless planet as it had been originally intended.