Former US Secretary of State Hillary Clinton on Tuesday lashed out at Republican senators for sending a letter to Iran over ongoing nuclear talks, accusing them of attempting to either sabotage President Barack Obama or help Tehran.

Clinton, widely seen as the eventual frontrunner to lead the Democrats' challenge in the 2016 presidential election, lambasted signatories who included several possible rivals in a future battle for the White House.

"One has to ask, what was the purpose of this letter?" Clinton told reporters during remarks at the United Nations in New York.

"Either these senators were trying to be helpful to the Iranians or harmful to the commander-in-chief in the midst of high stakes, international diplomacy.

"Either answer does discredit to the letters' signatories," added Clinton, describing the letter as "out of step with the best traditions of American leadership."

Clinton was speaking after 47 Senate Republicans made the unprecedented move of directly and publicly addressing Iran's leaders in a bid to scupper talks between Western powers and the Islamic Republic over the country's disputed nuclear program.

Republicans warned in the letter that any deal agreed before Obama leaves office in 2017 is "nothing more than an executive agreement" that could be struck down by Congress at a later date.

But Clinton stressed that the Obama administration was "in the midst of intense negotiations" with Iran over its nuclear program.

"Their goal is a diplomatic solution that would close off Iran's pathways to a nuclear bomb and give us unprecedented access and insight into Iran's nuclear program," she said.

But Republican Senator Jim Risch, a signatory of the letter, hit back at Clinton's criticism.

"It's nonsense to say that any US senator is a friend of Iran. Iran has no friends in the United States Senate," Risch said.

"She's heard all of us criticizing the madmen who run that country over and over and over again."

Clinton's comments came after the White House strongly condemned the letter, with Vice President Joe Biden branding it "dangerous."

The US State Department also voiced dismay. Spokeswoman Jennifer Psaki said the Republican move was "harmful to American security."

"It inserts these members into the middle of very sensitive negotiations, negotiations that have historically, for not just decades, but centuries, taken place between the president, the executive branch and foreign countries," Psaki said.