Messages are queued in the delivery queue with a "451 4.4.1 [internal] No valid hosts (too many connection failures)"
This is the result of multiple consecutive failures to connect to an SMTP host. The entire domain is failed and all delivery attempts are temporarily suspended with this message.
The exact conditions under which this occurs and how to resolve it are being researched.
Conditions under which this has been seen:
Scanner unable to deliver spam to quarantine due to improper MTA binding. This can be addressed by binding "Messages destined for the Control Center" to another IP. In the Control Center go to (Administration -> Configuration -> Select a host -> SMTP -> Advanced Settings -> Delivery).
Outbound delivery to specific hosts or to all hosts fails due to firewall configuration preventing establishment of an SMTP connection. This issue can be addressed by opening up and/or reconfiguring the firewall not to filter SMTP traffic.