451 4.4.0 Primary target IP address responded with 421 4.2.1 "Unable to connect"...

I have what I think is an unusual outbound email issue.  Most of our email sends just fine. We have a few addresses that are getting the following error in the Last Error column on the Exchange 2010 Queue Viewer:

451 4.4.0 Primary target IP address responded with 421 4.2.1 "Unable to connect". Attempted failover to alternative host, but that did not succeed. Either there are no alternative hosts or delivery failed to all alternative hosts.

Delivery Type: DnsConnectorDelivey

Most addresses deliver just fine but we are getting a few domain names that do not deliver at all (get hung up in the queue).

Running the Exchange Troubleshooting Assistant I get the following "Possible Root Cause Found":

'MSExchangeMailSubmission' service on server EAGLESBSSERVER is not discovering all servers with Hub Transport server role installed in the local Active Directory site with GUID 'fffdc295-cfe9-4c9d-83b4-0bdf0a48cf91'. This can be an indication that 'MSExchangeADTopology' discovery is failing to discover these servers due to object validation errors.

We only have one server (SBS2011)

How can I resolve this?

Thank you!
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Helao MwapangashaData Centre: Server EngineerCommented:

is your sbs server delivering to some sort of edge server or smart host?
ImImInAuthor Commented:
Helao MwapangashaData Centre: Server EngineerCommented:
error is normally a problem with end point delivery hence mail says in the queue.

verify u can telnet via port 25 to the ip that is giving you the error
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ImImInAuthor Commented:
cannot telnet but there are other addresses that get hung as well
Helao MwapangashaData Centre: Server EngineerCommented:
and these are destined for a different domain?

how are the permissions on your send connector?
ImImInAuthor Commented:
I think I was cahsing a goose, it looks like there may be an issue on the recipinets server?!?
Sorry for the troubler. I will post back if it ends up being something else.
ImImInAuthor Commented:
It appears that the reason for the mail delivery issue is due to blacklisting!  The odd thing is the blacklisting did not show up until today (MXToolbox) and the problem started 2 days (48+ hours) ago!

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Helao MwapangashaData Centre: Server EngineerCommented:
we live and we learn. glad you managed to sort it out.
ImImInAuthor Commented:
Thank you Helao! I appreciate your input!
ImImInAuthor Commented:
I did additional research and found solution by other means, was not getting what I needed from this question thread.
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