Whether the donations played any role in the approval of the uranium deal is unknown. But the episode underscores the special ethical challenges presented by the Clinton Foundation, headed by a former president who relied heavily on foreign cash to accumulate $250 million in assets even as his wife helped steer American foreign policy as secretary of state, presiding over decisions with the potential to benefit the foundation’s donors.

In a statement, Brian Fallon, a spokesman for Mrs. Clinton’s presidential campaign, said no one “has ever produced a shred of evidence supporting the theory that Hillary Clinton ever took action as secretary of state to support the interests of donors to the Clinton Foundation.” He emphasized that multiple United States agencies, as well as the Canadian government, had signed off on the deal and that, in general, such matters were handled at a level below the secretary. “To suggest the State Department, under then-Secretary Clinton, exerted undue influence in the U.S. government’s review of the sale of Uranium One is utterly baseless,” he added.

American political campaigns are barred from accepting foreign donations. But foreigners may give to foundations in the United States. In the days since Mrs. Clinton announced her candidacy for president, the Clinton Foundation has announced changes meant to quell longstanding concerns about potential conflicts of interest in such donations; it has limited donations from foreign governments, with many, like Russia’s, barred from giving to all but its health care initiatives. That policy stops short of a more stringent agreement between Mrs. Clinton and the Obama administration that was in effect while she was secretary of state.

Either way, the Uranium One deal highlights the limits of such prohibitions. The foundation will continue to accept contributions from foreign sources whose interests, like Uranium One’s, may overlap with those of foreign governments, some of which may be at odds with the United States.

When the Uranium One deal was approved, the geopolitical backdrop was far different from today’s. The Obama administration was seeking to “reset” strained relations with Russia. The deal was strategically important to Mr. Putin, who shortly after the Americans gave their blessing sat down for a staged interview with Rosatom’s chief executive, Sergei Kiriyenko. “Few could have imagined in the past that we would own 20 percent of U.S. reserves,” Mr. Kiriyenko told Mr. Putin.

“Should we be concerned? Absolutely,” said Michael McFaul, who served under Mrs. Clinton as the American ambassador to Russia but said he had been unaware of the Uranium One deal until asked about it. “Do we want Putin to have a monopoly on this? Of course we don’t. We don’t want to be dependent on Putin for anything in this climate.”

A Seat at the Table

The path to a Russian acquisition of American uranium deposits began in 2005 in Kazakhstan, where the Canadian mining financier Frank Giustra orchestrated his first big uranium deal, with Mr. Clinton at his side.

The two men had flown aboard Mr. Giustra’s private jet to Almaty, Kazakhstan, where they dined with the authoritarian president, Nursultan A. Nazarbayev. Mr. Clinton handed the Kazakh president a propaganda coup when he expressed support for Mr. Nazarbayev’s bid to head an international elections monitoring group, undercutting American foreign policy and criticism of Kazakhstan’s poor human rights record by, among others, his wife, then a senator.

Within days of the visit, Mr. Giustra’s fledgling company, UrAsia Energy Ltd., signed a preliminary deal giving it stakes in three uranium mines controlled by the state-run uranium agency Kazatomprom.

If the Kazakh deal was a major victory, UrAsia did not wait long before resuming the hunt. In 2007, it merged with Uranium One, a South African company with assets in Africa and Australia, in what was described as a $3.5 billion transaction. The new company, which kept the Uranium One name, was controlled by UrAsia investors including Ian Telfer, a Canadian who became chairman. Through a spokeswoman, Mr. Giustra, whose personal stake in the deal was estimated at about $45 million, said he sold his stake in 2007.

Soon, Uranium One began to snap up companies with assets in the United States. In April 2007, it announced the purchase of a uranium mill in Utah and more than 38,000 acres of uranium exploration properties in four Western states, followed quickly by the acquisition of the Energy Metals Corporation and its uranium holdings in Wyoming, Texas and Utah. That deal made clear that Uranium One was intent on becoming “a powerhouse in the United States uranium sector with the potential to become the domestic supplier of choice for U.S. utilities,” the company declared.

(In a statement issued after this article appeared online, Mr. Giustra said he was “extremely proud” of his charitable work with Mr. Clinton, and he urged the media to focus on poverty, health care and “the real challenges of the world.”)

Though the 2008 article quoted the former head of Kazatomprom, Moukhtar Dzhakishev, as saying that the deal required government approval and was discussed at a dinner with the president, Mr. Giustra insisted that it was a private transaction, with no need for Mr. Clinton’s influence with Kazakh officials. He described his relationship with Mr. Clinton as motivated solely by a shared interest in philanthropy.

As if to underscore the point, five months later Mr. Giustra held a fund-raiser for the Clinton Giustra Sustainable Growth Initiative, a project aimed at fostering progressive environmental and labor practices in the natural resources industry, to which he had pledged $100 million. The star-studded gala, at a conference center in Toronto, featured performances by Elton John and Shakira and celebrities like Tom Cruise, John Travolta and Robin Williams encouraging contributions from the many so-called F.O.F.s — Friends of Frank — in attendance, among them Mr. Telfer. In all, the evening generated $16 million in pledges, according to an article in The Globe and Mail.

“None of this would have been possible if Frank Giustra didn’t have a remarkable combination of caring and modesty, of vision and energy and iron determination,” Mr. Clinton told those gathered, adding: “I love this guy, and you should, too.”

But what had been a string of successes was about to hit a speed bump.

Arrest and Progress

By June 2009, a little over a year after the star-studded evening in Toronto, Uranium One’s stock was in free-fall, down 40 percent.

By June 2009, a little over a year after the star-studded evening in Toronto, Uranium One’s stock was in free-fall, down 40 percent. Mr. Dzhakishev, the head of Kazatomprom, had just been arrested on charges that he illegally sold uranium deposits to foreign companies, including at least some of those won by Mr. Giustra’s UrAsia and now owned by Uranium One.