From past experience, these errors usually mean there is an underlying problem in the .NET environment on the affected server. I usually recommend starting with Windows Updates and a .NET repair, followed by a reinstall of the .NET components (and re-registering them in Windows) if all else fails.
If you run other .NET sites or services on the server that also rely on .NET you can try moving SmarterMail to its own isolated environment to narrow down whether those problems are being introduced by SmarterMail or the other services you have running there.
Since comments above noted virtualized environments; we have also seen some environments have better results with memory usage when not using dynamic memory, so I recommend setting a hard limit temporarily to see if this helps. If you need a hand tracking this down please don't hesitate to submit a ticket with us and we'll do our best to get you pointed in the right direction!
Kyle Kerst
IT Coordinator
SmarterTools Inc.
www.smartertools.com