US president Barack Obama defended the nuclear agreement with Iran as a "once-in-a-lifetime opportunity" to prevent a nuclear bomb and bring longer-term stability to the Middle East.
He insisted the US would stand by Israel if it were to come under attack, but acknowledged that his pursuit of diplomacy with Tehran has caused strain with the close ally.
"It's been a hard period," Mr Obama told The New York Times.
He added that it is “personally difficult” for him to hear his administration accused of not looking out for Israel’s interests.
Now in his seventh year in office, Mr Obama cast the Iran talks as part of a broader foreign policy doctrine that sees American power as a safeguard that gives him the ability to take calculated risks.
"We are powerful enough to be able to test these propositions without putting ourselves at risk," he said, citing his overtures to Cuba and Burma as other examples of his approach.
The president’s comments come days after the US and other world powers reached a tentative agreement to curb Iran’s nuclear programme in exchange for sanctions relief.
The framework cleared the way for negotiators to work out technical details ahead of a June 30 deadline for a final deal.
Mr Obama argued that successful negotiations presented the most effective way to keep Iran from obtaining a nuclear weapon, but insisted he would keep all options on the table if Tehran were to violate the terms.
“I’ve been very clear that Iran will not get a nuclear weapon on my watch, and I think they should understand that we mean it,” he said.
“But I say that hoping that we can conclude this diplomatic arrangement — and that it ushers a new era in US-Iranian relations — and, just as importantly, over time, a new era in Iranian relations with its neighbours.”
The president said there are many details that still need to be worked out with the Iranians and warned there would be “real political difficulties” in implementing an agreement in both countries.
He reiterated his opposition to legislation that would give the US Congress final say in approving or rejecting a deal, but said he hoped to find a path to allow Congress to "express itself".
The White House plans an aggressive campaign to sell the deal to Congress, as well as to sceptical Arab allies who worry about Iran's destabilising activity in the region.
The president has invited leaders of six Gulf nations to Washington this spring and said he wanted to "formalise" US assistance.
On the substance of the Iran framework agreement, Mr Obama outlined more specifics of how the US would seek to verify that Tehran was not cheating.
He said there would be an “international mechanism” that would assess whether there needed to be an inspection at a suspicious site and could overrule Iranian objections.
The nuclear talks have marked a remarkable shift in the frozen relationship between the US and Iran.
It has become normal for officials from both countries to communicate and hold face-to-face meetings.
Mr Obama is yet to meet Iranian president Hasan Rouhani, though they did speak on the phone. He has also exchanged letters with Iran's supreme leader Ayatollah Ali Khamenei.