Think Twitch has most of it. Power plants were not effective enough in producing the thrust required to become effective against single engined fighters. The 110 was an attempt to produce a long range fighter. In that it failed. But it was one of many attempts to deal with the same problem.
The problem was simple. Fighters (or Pursuit Aircraft) were and are (to a certain extent) defensive aircraft. Bombers are offensive weapons. Doctines in the 30s and early 40s called for fighters to be Interceptors or Army support aircraft. Bomber escort was not considered a major part of their job description (for lack of a better word) because theories said the bomber "would always get through". Either by speed (The Blenheim) or by firepower (the Flying Fortress), the bomber would get through. Reality was different. The Blenheim was nowwhere near fast enough nor was the B17 heavily armed enough.
The concept of a long range fighter was worked on by many countries but, and somewhat oddly, only put into mass production before general hostilities by Fascist or Axis Countries. A point that speaks volumes. Anyway, the Germans and Japanese both worked on the idea of a long range, air superiority fighter. The Germans came up with the 110, the Japanese with the Zero. Both had serious drawbacks that later came up in combat operations.
The long range fighter is a an Offensive Weapon. It carries the fight over the enemies bases and production centers. The Germans and Japanese introduced production aircraft to the idea but it really fell the the USAAF to get the job done right. In practice, the Mustang was the aircraft that gain air superiority. The Mustang's flaws may've shown up if it was in an Interceptor role, then again, maybe not. But as a long range escort, intruder and air supremecy platform, it was outstanding.
I'm so-so on the idea that the P38 was a great air supremecy weapon. It did it well in the Pacific but less effective in Europe. The Mustang did it well in both Theatres. The T-Bolt had decent leggs when developed, but not on the same level as the Mustang.
Lastly, I like the Whirlwind. Thought it was a very cool looking aircraft. Wonder how it would've performed with better engines.