Ferrocenophanes undergo ring-opening polymerization

duces polymer strands with molecular weights on the order of 80,000.

The poly(ferrocenylethylenes) have potential as electroactive materials and as preceramic polymers, Manners says. Their electrical properties, for instance, indicate that the metal atoms, separated as they are by two-atom spacers, interact much less than in the poly(ferrocenylsi-lanes). The poly(ferrocenylethylenes) thus might be useful as redox polymers. Manners also is interested in replacing the -CH2CH2- bridge with an olefinic group to increase the metals7 interaction.

If s too early to know what uses the new polymers may find, but Manners' experience with the silicon analogs may be instructive. He says the poly(ferro-cenylsilanes) have already attracted "sig­nificant industrial interest" because of their ease of preparation from simple starting materials and their potentially useful high-performance properties. For example, Manners notes that they can be reversibly oxidized and reduced, and they change color in the process. This might lead to their application in elec­trode modification or display devices.

They also seem to have potential as precursors to metal-containing ceram­ics. When pyrolyzed at 500 °C under nitrogen, the silicon-ferrocene poly­mers yield iron silicon carbide ceramics that are magnetic [/. Chem. Soc, Chem. Commun., 1993, 523].

One potential problem with this antici­pated use is that cyclopentadienyl groups tend to decompose at elevated tempera­tures, according to chemistry professor Harry R. Allcock of Pennsylvania State University, University Park, who has had some experience in this area. The upshot, he says, is that "you get a hodgepodge of

decomposed species in the solid state, rather than a dis­crete ceramic, which is what people are looking for." Al­though some polymers can be converted into ceramics, he tells C&EN, "I don't think there's any evidence that useful ceramics [can be made] from materials that have ferrocene units in them."

Allcock believes that if Manners' polymers show evidence of having useful electronic properties, that's most likely where their technological future will lie.

In any case, a consortium of Canadian companies has awarded Manners and his Toronto collaborator, polymer scien­tist G. Julius Vancso, a grant to explore the properties and applications of these polymers. Thus far, Manners' work has been funded by the Petroleum Research

The 20th century lies in the middle of an interglacial period—the relatively warm interval between two ice ages. The present interglacial, called the Holocene, is one of great climatic stability.

However, surprising information from a new ice core drilled in the thickest part of Greenland's ice sheet indicates that the stability of the Holocene—the past 10,000 years—may have been the excep­tion rather than the rule. Evidence pre sented in two articles in Nature [364, 203 and 218 (1993)] indicates that except for the Holocene, the past 260,000 years had a highly unstable climate. This evidence comes from analyses of chemical and physical properties of the 3000-meter ice core.

What most surprises scientists is that the previous interglacial period, long' thought to have had relatively even tem­peratures, seems to have been punctuat­ed by episodes of severe cold, which be­gan extremely rapidly and lasted from decades to centuries.

According to James W. C. White of the Institute of Arctic & Alpine Research at the University of Colorado, Boulder, it would be difficult to exaggerate the im­portance of the new ice core data. These data are from what is called the Green­land Ice-core Project (GRIP).

Fund, the Natural Science & Engineer­ing Research Council of Canada, and the Ontario Center for Materials Re­search.

In his search for strained organome-tallic monomers that will undergo ring-opening polymerization, Manners is now looking beyond ferrocene deriva­tives. His group has found, for exam­ple, that some ruthenocenophanes fit the bill. Because of the larger size of a ruthenium atom compared to iron, these sandwich compounds have even greater ring-tilt angles. The group's record thus far is 29.6° for the unsubsti-tuted ruthenocenophane with an ali­phatic two-carbon bridge.

To be sure, using ring strain to poly­merize metallocenophanes is "a good idea," Allcock agrees. If s such a good idea, in fact, that other groups, both in­dustrial and academic, have begun to explore it. So Manners' monopoly of the area, as reflected in the chemical litera­ture, may not last much longer.

Ron Dagani

For many years, scientists believed that, during glacial eras, sharp tempera­ture swings took place over decades, triggered by massive glaciers or sea ice. They also assumed from the meager available data that previous interglacial eras, like the current interglacial Ho­locene period, were stable. But evidence from the GRIP ice core, which has much higher resolution than previous data, in­dicates that in the North Atlantic region, at least, average temperatures during the Eemian—the previous interglacial peri­od 115,000 to 135,000 years agc^-varied as much as 10 °C in a decade or two.

According to GRIP ice core data, aver­age global temperatures during the warm part of the Eemian were 4°C higher than today. During those warm years, England was tropical, with hippo­potamuses wallowing as far north as the River Tees. But the Eemian was punctu­ated by sudden and intense cold spells, when temperatures in the North Atlantic region plunged in a decade or two to levels typical of a midglacial period and stayed that way sometimes for decades, sometimes for centuries. The persistence of these cold events "indicates that shifts in ocean circulation were involved," ac­cording to the GRIP team members.

The only other ice core that has pro-

Ice core data show earlier climatic instability

AUGUST 2,1993 C&EN 23

vided information about the Eemian is the Vostok core drilled in Antarctica in the mid-1980s. Because very little snow fell in Antarctica during the Eemian (or at any other time), the Vostok layers for that period are thin and have been re­solved for only centuries, not decades. Therefore, Eemian temperatures de­duced from the Vostok data are smooth and relatively stable, although high-resolution sampling in the future may yield information on the decadal scale.

At least two periods of unusual cli­mate have occurred during the Ho-locene, one called the Little Ice Age

from 1550 to 1850, when the canals in the Netherlands froze over for most of the winter and Alpine glaciers ad­vanced, and the other, known as the medieval warm period, when the Vi­kings settled the coast of Greenland. But these climate changes were very moderate compared with the wild tem­perature swings that seem to have oc­curred during the Eemian.

The two international groups of scien­tists who published articles about the GRIP ice core data deduced tempera­tures from four types of measurements. They used the ratios of 18Q to 16Q iso­

topes in the ice layers as one indication. The higher the temperature when polar ice is formed, the higher the ratio. It is expressed as δ180, the relative deviation of the 180:160 ratio in an ice sample from the ratio in standard mean ocean water.

They employed the calcium(II) ion content of the ice layer as another clue to past temperatures. The higher the calci­um ion content, the lower the tempera­ture. Calcium ion levels go up as Earth's atmosphere becomes more dusty. The atmosphere grows more dusty as Earth cools, causing the temperature difference between the poles and the equator to widen and winds to increase. Also, dur­ing glacial periods as ocean water.is tak­en up into glaciers and ice caps, sea lev­el falls and exposes the soil on continen­tal shelves to the wind.

A third indication of past tempera­tures the scientists used is the conductiv­ity of the ice layer. This depends mostly on the free acid levels in the ice, which in turn depend on the buffering provided largely by calcium carbonate in atmo­spheric dust. The acid is primarily sulfu­ric acid from marine phytoplankton. The GRIP team members found that the δΊ80 values and the conductivity levels in the ice layers were highly correlated and that calcium ion concentrations showed a strong anticorrelation with these data.

The GRIP team also used the levels of methane trapped in air bubbles in the ice layers as clues to temperature and to demonstrate the global nature of the cli­mate changes. When Earth grows warm­er, marshes, which are sources of meth­ane, become more extensive. So far, very few measurements of methane have been completed for the GRIP ice core. All of these techniques are standard methods of deducing past climate from ice core data.

The GRIP team dated the ice layers by counting layers for the first 14,500 or so years. Deeper than that the layers are in­distinct and cannot be counted. So for the years from 14,500 to 260,000 before present, the team used ice flow model­ing to relate ice core depth to year of for­mation.

Team members verified the time scale deduced from modeling by comparing major climatic events in their new data with important events found in other measures of climate, such as data from the Vostok ice core; pollen records that go back 60,000 years and are dated with carbon-14; and ocean sediment cores, which give indications of climate through

24 AUGUST 2, 1993 C&EN

SCIENCE/TECHNOLOGY

Three measures show Eemian period correlation

Reprinted with permission from Nature [364, 204 (1993)]; ©1993 Macmillan Magazines Ltd.

The δ180 measurements for the Eemian era in the Greenland Ice-core Project ice core correlate fairly directly with conductivity measurements. And as ex­pected, calcium(II) ion concentration data show nearly the opposite trend. The δ180 data give a measure of Greenland's temperature when the ice was formed. Higher (less negative) values indicate higher temperatures. (To calcu­late δ180, the 180:160 ratio in the ice layer is divided by the 180:160 ratio in mean standard ocean water; one is subtracted from the quotient and the result is multiplied by 1000.) Because of the physics of ice formation, ocean water always has a higher 180:160 ratio than ice. Calcium ion concentrations, mea­sured in micromoles, depend on the dustiness of the atmosphere when the ice was formed and tend to increase with cooler temperatures. The conductivity of the ice core layer, measured in microsiemens per meter, depends largely on the amount of free acid in the ice. This, in turn, depends largely on the amounts of sulfuric acid produced by marine phytoplankton and the amount of dust (mainly calcium carbonate) available to buffer the acid. Consequent­ly, the conductivity of the ice goes down as the dustiness and calcium ion levels go up. As the depth of the ice core increases, each meter represents a longer time span because the weight of ice above compresses the ice layers.

many glacial and interglacial periods. Be­cause benthic life and ocean currents scramble the layers of sediment on the sea bottom, ocean cores have a resolution of only about 1000 years, and therefore give only broad indications of average climate over millennia.

Another ice core, the GISP2 core, has been drilled about 20 miles from the GRIP ice core, but has not yet been ful­ly analyzed. Oxygen-18 data from the GISP2 core, which will be complete in about six months, will help verify the temperatures and time scale deter­mined for the GRIP core.

The new results from the GRIP ice core show that the Holocene has had es­sentially only one climate state, whereas the Eemian had three distinct states, White says. 'The middle [temperature] state matches our own Holocene climate, but a significantly colder and a signifi­cantly warmer state existed in the Eemi­an," and its climate made quantumlike leaps between these states, he says.

White compares these climate states to the energy levels that are possible for electrons in an atom. Electrons can leap from one level to another but cannot change their energy gradually and lin-

A new synthetic technique that com­bines chemical and enzymatic aspects could ease one of the most difficult con­struction jobs in chemistry—making gly-copeptides and glycoproteins on a large scale.

Glycopeptides and glycoproteins (car-bohydrate-peptide and carbohydrate-protein conjugates) are among the most complex natural compounds. They play a vital role in virology, immunology, bi­ological recognition, biomolecular trans­port, and other processes.

But laboratory synthesis of glycopep­tides and glycoproteins is a formidable undertaking, requiring chemical protec­tion and subsequent deprotection of nearly all functional groups on the pep­tide, and almost all hydroxyl groups on the carbohydrate as well. Small amounts of the conjugates can be made syntheti­cally, but larger quantities that would be useful for biomedical research are diffi­cult to obtain.

Large-scale synthesis is still largely impractical because of the tediousness of the many protection and deprotec­tion steps required.

early. Eemian temperatures were simi­lar. Rather than increasing or decreasing gradually, they seemed to leap from one preferred state to another. "We don't know which is the norm for interglacial periods: the stable, one-state Holocene or the multiple-state, rapidly changing Ee­mian," White writes in Nature [364, 186 (1993)]. "These new data show we're still learning the fundamentals of how climate works," he adds.

The average global temperature dur­ing the Eemian was 2 °C warmer than it is today. If the additional warmth of the Eemian triggered climate instability, this raises questions about whether current global warming might push the present climatic regime into an unstable state, White says. "Given our ongoing 'global experiment' of increasing greenhouse gas concentrations via fossil fuel burn­ing, is the Eemian warm state a glimpse at our future climate?" White asks.

The new information suggests that if present greenhouse gas emission trends continue, Earth's climate could be thrown into wild swings that would make the on­going Mississippi River flood look like child's play.

Bette Hileman

Now, chemistry professor Chi-Huey Wong, postdoctoral researchers Peng Wang and Matthias Schuster, and grad­uate student Pamela Sears of Scripps Research Institute, La Jolla, Calif., pro­pose that enzymatic formation of pep­tide bonds be combined with chemical

Wong: chemical-enzymatic synthesis

steps to ease the task of glycopeptide synthesis considerably [/. Am. Chem. Soc., 115, 5893 (1993)].

There is a major problem in achieving such a marriage of techniques. Enzymes such as proteases, which normally cleave peptides in aqueous solution, work in reverse in organic solvents and can thus be used to form peptide bonds in organic solution. But nobody has used proteases for glycopeptide synthesis be­cause glycosylated peptides are not sol­uble in organic solvents.

To skirt this dilemma, Wong and co­workers "engineered" an enzyme so it would catalyze peptide synthesis in wa­ter without the need for protecting group chemistry. This decidedly non-trivial effort yielded two variants of the protease enzyme subtilisin BPN'.

To construct glycopeptides with the engineered enzymes, the researchers first synthesize a core glycopeptide structure by conventional chemical meth­ods. They elongate the peptide chain with the modified subtilisin BPN's, using the enzymes to add peptide or glycopeptide fragments to the core structure via new peptide linkages. The sugar chain can also be extended, either prior to or after pep-tide-chain extension, by using glycosyl-transferase enzymes.

Wong points out that the subtilisins have very broad specificity, accepting almost every amino acid as a sub­strate—except proline, which can be positioned inside a glycopeptide frag­ment, if necessary, prior to enzymatic coupling. Hence, there are few restric­tions on the versatility of the technique, he says.

The glycopeptides described in the paper are not very big. But Wong's group has since gone on to synthesize a glycopeptide containing the tetrasac-charide sialyl Lewisx and 10 amino ac­ids.

Perhaps the leading researcher in chemical synthesis of glycopeptides has been organic chemist Horst Kunz of Johannes Gutenberg University, Mainz, Germany. Kunz and coworkers developed protecting group techniques that have made glycopeptide synthesis feasible, and have used these tech­niques to synthesize peptide-T deriva­tives and other glycopeptides.

Other key contributions have been made by chemistry professors Bertram O. Fraser-Reid of Duke University, Sam­uel J. Danishefsky of Memorial Sloan-Kettering Cancer Center and Columbia

Glycopeptide synthesis uses engineered enzymes

AUGUST 2,1993 C&EN 25