The Ukrainian was beaten 6-3 6-3 by world number 62 Ivan Dodig of Croatia, ranked 40 places below him.
There were no such problems for the other two seeds in action, Sam Querrey and Xavier Malisse.
Third seed Querrey progressed from his all-American clash with Michael Russell when his opponent withdrew with an apparent injury. Querrey was leading 6-2 2-2 at the time.
Malisse of Belgium saw off Alejandro Falla of Colombia 6-3 6-3, but his compatriot Steve Darcis was ousted 7-6 (7/5) 6-3 by Russia's Evgeny Donskoy.