We had an interesting issue with queues building up to remote sites. In queue viewer we noted errors sending mail to different remote sites as per below:
451 4.4.0 Primary Target IP Address responded with: “235 00000xxxxxxxxx”
And in the Event Viewer we noticed event ID 1035 , MSExchangeTransport
At first we thought the issue has to be on the specific Exchange 2010 server trying to send the mail as it was the only server in the DAG that could not send mail to the remote servers. However, the problem was still present after restarting the Hub Transport Service on the server experiencing the above issues.
As a shot in the dark we restarted the SMTP and Hub Transport Services on the remote servers (to where the mail is destined) and the errors disappeared and the mail was sent to the remote servers.