If you mean manually send the keystroke, then something like Putty would be fine.

If you mean automated sending of the keystroke, pass.

Normally you would use a receipt printer for this and have the cash drawer connected by a simple RJ11 plug which sends voltage to a solenoid in the drawer to open it - that is how I've always set this up as most POS software can trigger the kicker this way. Doing it via the serial port is considered an older method in my books and most POS software has the ability to kick the drawer but normally requires a string to do so in most cases.

This is very dependent on the type of cash drawer you're using. If this is for retail I would only allow for the cash drawer to open with logging either internally on the PC via the POS software or a receipt being printed out to write the reason of why the cash drawer has been opened. This is almost a standard in the industry if multiple staff is using it as you've got an audit trail. I would never recommend assigning a key to do this without the POS software being involved to log these events (as this is how money goes missing).

We have a usb trigger that acts as a com port :)