U.S. president Donald Trump targeted Khamenei and other top Iranian officials with sanctions on Monday, taking an unprecedented step to increase pressure on Iran after Tehran's downing of an unmanned American drone.
"We call on the regime to abandon its nuclear ambitions, change its destructive behaviour, respect the rights of its people, and return in good faith to the negotiating table", Trump said in a statement.
Tensions between the two countries have escalated steadily since May 2018, when Mr Trump abandoned the landmark 2015 nuclear deal between Iran and six world powers, and began reinstating sanctions to force Iran to renegotiate the accord.
Meanwhile, Iran hinted on Monday that it could be willing to discuss new concessions with Washington if the United States were to lift sanctions and offer new incentives.
He signed the order in presence of Treasury Secretary Steven Mnuchin. "And here we are sitting with 150 dead people that would have taken place probably within a half an hour after I said, 'Go ahead.' And I didn't like it". After the downing of the drone, Trump pulled back from the brink of retaliatory military strikes but continued his pressure campaign against Iran.
Iran denies seeking nuclear weapons and refers to a decree issued in the early 2000s by Khamenei that bans the development or use of nuclear weapons.
Tensions have flared following the attacks on oil tankers in the Gulf, Iran's downing of the drone last week, and repeated attacks on Saudi airports and oil installations by Yemen's Iran-aligned Houthis.
He said Khamenei was ultimately responsible for what Trump called "the hostile conduct of the regime" in the Middle East.
The latest sanctions are aimed at denying Iran's leadership access to financial resources and blocking them from using the USA financial system or assets.
Moreover, any foreign financial institution that knowingly facilitates a significant financial transaction for entities designated under this Executive Order could be cut off from the USA financial system. "We don't even need to be there".
Mr Hook said a deal would address Iran's nuclear programme, regional aggression and detention of dual nationals.
"Freedom of navigation is tantamount", he said in a tweet after meeting King Salman bin Abdulaziz.
Iran has denied any involvement.
One of the Iranian president's top advisers indicated Iran was open to a new deal with the U.S. but said concessions beyond the 2015 nuclear deal would have to be met by the Americans.
The United States launched cyberattacks targeting Iranian missiles and rockets after the Islamic Revolution Guards Corps shot down a U.S. Navy RQ-4A Global Hawk drone last week, Iran media reported.
The Strait of Hormuz is a vital shipping line allowing access to the Arabian Gulf and has been the centre of deteriorating relations with Iran since April.
"Treasury will continue to aggressively target the senior leaders and the financial apparatus sustaining this malign activity".
"These measures represent a strong and proportionate response to Iran's increasingly provocative actions", Trump said.