Last weekend, Vice President Joe Biden said the United States was ready for one-on-one negotiations with Iran about its nuclear program “when the Iranian leadership, supreme leader, is serious.”

On Thursday, that supreme leader, Ayatollah Ali Khamenei, sounded seriously belligerent when he said that Iran isn’t interested in a direct dialogue with the U.S.

That rejection was a bit of a surprise. Earlier this week, both Iranian President Mahmoud Ahmadinejad and Foreign Minister Ali Akbar Salehi had expressed interest in Vice President Biden’s offer.

But as Khamenei’s “supreme leader” title shows, he’s the one in charge.

And after the U.S. further tightened economic sanctions against Iran on schedule Wednesday, the ayatollah was supremely peeved. As he put it Thursday during a speech to Iranian air force commanders:

“Does imposing, in your own words, ‘crippling sanctions’ show good will or hostility? Iran will not accept to negotiate with he who threatens us with pressure.”

However, Khamenei did indicate that Iran would move forward to another round of negotiations with the P5+1 group (the U.S., Britain, China, France and Russia — plus Germany), starting Feb. 26 in Kazakhstan.

Unfortunately, considering the futility of previous talks in that series, it would be naive to imagine Iran suddenly backing off from its nuclear-weaponry ambitions.

Indeed, President Ahmadinejad, during a visit to Egypt this week, boasted that Iran is “now a nuclear power” — though he added that it doesn’t plan to attack Israel.

It would be foolish to trust either assertion, especially in light of Ahmadinejad’s many past proclamations that the destruction of Israel looms.

At least Ahmadinejad’s efforts to mend Iranian fences with Egypt didn’t go well. Protesters even threw shoes at him Tuesday at a Cairo mosque.

But Khamenei and Ahmadinejad aren’t the only big shots who have recently sent mixed messages about U.S.-Iran relations.

Last week, Chuck Hagel, President Barack Obama’s nominee for Secretary of Defense, stunned the Senate Armed Services Committee by calling the Iranian regime an “elected, legitimate government.”

Hagel strangely added that he supported “the president’s strong position on containment” of Iran’s nuclear program.

Moments later, after somebody handed him a note, Mr. Hagel said: “I misspoke and said I supported the president’s position on containment. If I said that, I meant to say we don’t have a position on containment.”

Committee Chairman Carl Levin, D-Mich., tried to help the president’s Pentagon pick: “We do have a position on containment, and that is we do not favor containment. I just wanted to clarify the clarify.”

Mr. Hagel also clarified that Iran’s is not a “legitimate” government but a “recognized” member of the United Nations, explaining: “That’s what I should have said.”

Yet no clarification is needed for this all-too-clear pattern: Iran has long been playing for time in its relentless march toward a nuclear arsenal.

As for the effectiveness of those economic sanctions, Thursday’s Wall Street Journal reported: “Iranian banks have managed to bypass a ban imposed last year that was intended to cut its access to global financial transactions through the world’s most-used electronic-payment system, known as Swift, according to executives who run the system.”

The Obama team should keep that end run in mind as it assesses the chances of sanctions alone deterring Iran’s nuclear aims.

President Obama has repeatedly said the U.S. will never allow Iran to obtain nuclear weapons.

But the crucial question of how to prevent that chilling outcome remains unanswered.