US Secretary of State John Kerry said talks on Iran's nuclear programme would continue through the night in an effort to resolve
"tricky issues" as a deadline for a long-awaited deal looms.
"There still remain some difficult issues," Mr Kerry told a CNN reporter as he walked in his luxury lakeside hotel in the Swiss town of Lausanne.
"We are working very hard to work those through. We are working late into the night and obviously into tomorrow."
A deadline for the framework on a nuclear deal with Iran deal expires at midnight tomorrow and officials appealed to all parties to make a huge final effort.
For days Iran, the United States, Britain, France, Germany, Russia and China have been trying to break an impasse in negotiations, aimed at stopping Tehran having the capacity to develop a nuclear bomb, in exchange for an easing of United Nations sanctions that are crippling its economy.
But earlier, officials at the talks in the Swiss city of Lausanne said attempts to reach a framework accord, which is intended as a prelude to a comprehensive agreement by the end of June, could yet fall apart.
Negotiators from all parties appeared increasingly pessimistic.
"If we don't have some type of framework agreement now, it will be difficult to explain why we would be able to have one by June 30," said a Western diplomat.
He said three major sticking points must be resolved if Iran and the six powers are to secure the deal before 31 March, and it is unclear whether those gaps could be filled.
The diplomat said the most difficult issues related to the duration of any limits on Iranian uranium enrichment and research and development activities after an initial ten years, the lifting of the sanctions and the restoring of them in case of non-compliance by Iran.
"It seems that we have an accord for the first ten years, but with regard to the Iranians the question of what happens after is complicated," the official said on condition of anonymity, adding: "I can't say what the final result will be."
German Foreign Minister Frank-Walter Steinmeier said there had been "some progress and some setbacks in the last hours".
Highlighting the general mood, a diplomat quoted by Chinese news agency Xinhua said the atmosphere today had turned from "optimism" to "gloom" among negotiators.
An adviser to Iran's Supreme Leader Ayatollah Ali Khamenei criticised the powers.
"Our negotiating team are trustworthy and compassionate officials that are working hard, but they should be careful with the enemies' deceptive and skillful tactics," the adviser, Ali Akbar Velayati, told Fars news agency.
In addition to US Secretary of State John Kerry, Iranian Foreign Minister Mohammad Javad Zarif, Steinmeier, British Foreign Secretary Philip Hammond, French Foreign Minister Laurent Fabius, China's Wang Yi and Russia's Sergei Lavrov gathered at a 19th-century hotel overlooking Lake Geneva.
After the first meeting since November of all the ministers, Mr Lavrov returned to Moscow for an engagement, though officials said he would return if there was something to announce.
Israeli Prime Minister Benjamin Netanyahu, who has campaigned against the negotiations, said in Jerusalem that the agreement being put together in Lausanne sends the message "that Iran stands to gain by its aggression".