@dt-mor: It sounds like you have created a database that’s much too large for the memory resources of your computer. The total number of words in a database (displayed in File > Database Properties) is a more meaningful measure of database size than the database file size.
An alternative approach is to create multiple topical databases, each of which has a total word count that leaves enough free RAM available for the computer to carry out procedures at full speed, without resorting to using Virtual Memory swap files.
For example, on a Mac with 4 GB installed RAM my rule of thumb would be to keep the total word count of all open DEVONthink databases below 40,000,000. Even so, it may be necessary to monitor free RAM use over time, to avoid slowdowns caused by data swapping between RAM and Virtual Memory swap files on disk. Safari (and perhaps other browsers) can be a memory hog, especially if multiple tabs are used; quitting the browser occasionally can restore free RAM.
Given the current size of your database, the best approach to splitting it would be to select some of the content, choose File > Export > Files & Folders and create a new Finder folder to hold exported content, then confirm the export. Afterwards, delete the selected material and empty the DEVONthink Trash. Continue doing that (saving the exports into different Finder files) until you have reduced the total word count of the current database to an acceptable level.
At that point, you can create a new, empty database and import (File >Import > Files & Folders) the contents of one of the Finder folders that holds previously exported material.
Obviously, you will not want to open all of those “split” databases simultaneously. Instead, treat them like information Lego blocks.
Although in your circumstance you will not be able to open and search across all of your databases within DEVONthink, you will be able to do so using Spotlight. By default, each of your databases provides indexes of its contents to Spotlight. When you do a Spotlight search, choose the option to view all results. Items contained in your DEVONthink databases will display the blue ammonite shell icon. Select one and press the Space bar to view it in Quick Look, or double-click it to open it in its DEVONthink database.