Category Archives: Chemistry

National Organic Symposium. Tuesday Morning.

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Bad day for Th’ Gaussling to be away. The hounds are snapping at my heels at work.

I managed only to see Eric Jacobsen‘s talk on catalytic urea chemistry. Jacobsen’s system is pretty much a chiral proton ligand that can carry along a nucleophilic counter anion. Configured differently, urea’s and thiourea’s with BARF groups on the nitrogen can coordinate with chloride. This can lead to the abstraction of chloride to give a carbenium ion that can then participate in a enantioselective Pictet-Spengler type reaction. 

Jacobsen’s system resembles a radically stripped down enzyme in terms of 3-point binding interactions by hydrogen bonding.  Where Jacobsen went askew is the use of calculations to justify his mechanistic model. The models did not include solvent interactions when affording only 0-2 kcal/mol (!!) differences in energy. Naturally this did not set well with certain distinguished members of the Audience.  The ΔΔG’s did not correlate with the ee’s at all either.

A certain J.D. Roberts took great exception to Jacobsen’s molecular modeling results, resulting in the spectacle of a Harvard Professor frantically qualifying his slides and words as he back pedalled for all he was worth. There was some actual contrition there on the stage. It was quite a thing to see. There but for the grace of God go I.

National Organic Symposium. Monday Morning.

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The speakers for the morning of June 8th were Bob Grubbs and Magid Abou-Gharbia. As usual, Bobby Grubbs’ talk was concerned with the latest wonders of olefin metathesis. We saw ATM’s of molecular Cheerios. Pretty cool, actually. Grubbs got the trip to Stockholm for a reason and the work of his group continues to produce molecular wonders.  He was able to demonstrate the production of rings with degrees of polymerization in excess of 5000.  Using NMR and a carefully chosen ring monomer, they could sort out linear polymers from cyclic polymers. Linear polymers will thread a crown ether while the cyclic form will not. By attaching a crown ether (24-crown-8 ??) to polystyrene beads, they could collect and physically separate the linear from the cyclic forms. They were also producing brush polymers.

Prof. Magid Abou-Gharbia, Temple University, gave a talk with lots of fascinating insights into some current thinking on industrial drug discovery. At least from the point of view of a former Wyeth guy. I have been away from the pharma-related work for a number of years now and haven’t really missed it. But his talk has revived enthusiasms in me that have been in a long slumber. 

Anyway, he described the development of the anti-depressant Effexor and their efforts to keep the molecule simple and free of excessive stereocenters. Studies of the metabolism of Effexor lead to the discovery of the des-methyl analog, now called Pristiq.

Concerning High Throughput Synthesis (HTS)-

“… you’re going to get a lot of decorated molecules, but they are not going to be biopharmaceutically useful.”

Abou-Gharbia lamented the languishing of natural products chemistry. He gave some examples of Rapamycin work, which according to his presentation, was originally isolated from a soil sample from Easter Island.  Much productive work apparently has been derived from the modification of this macrocycle. It’s all in the literature.

One of the main take-away lessons from Abou-Gharbia is that workers shouldn’t get too focused on SAR. His advice was that structure-property relationships need an early examination as well. Dual optimization. If the bioavailability is low, then the in vivo activity will not match the in vitro activity- an expensive and time consuming realization.

Organic Symposium

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Despite my previous gritching about it and despite trying to stay below the radar at work, the boss has requested and required that I attend the Organic Symposium at CU Boulder. I’ll bop over there later today to register and walk the poster session. Maybe there will be some useful grist for the blogmill.

No better reminder of the scientific pecking order than to skuttle around in the shadows of the great grant writers of our time. A certain speaker with a Nobel Prize casts a shadow so large that it is reported to weigh nearly 5 kilograms. Fancy that!

Thermochemical Snipe Hunt

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Spent the better part of the day hunting snipe in the chemical literature. I’ve been looking for some English language literature relating to the Yoshida explosive potential correlation between DSC heat of formation and DSC onset temperature. I have some sketchy relationships from Yoshida in Chemical Abstracts CAN 108:58900 –

Shock Sensitivity = log (QDSC) – 0.72*log(TDSC-25) – 0.98

Explosive Potential = log (QDSC) – 0.38*log(TDSC-25) – 1.67

QDSC is the magnitude of the exotherm as measured by DSC (presumably in J/g, not J/mol), and TDSC is the onset temp also determined by DSC. A separate reference suggests that compositions with EP>0 are potentially explosive.

I want some better grounding in the assumptions going into the correlation before I pony up my own results. This is potentially a very useful relationship in reactive hazards work and something I can do in the lab myself.

It’s a pity I do not speak Japanese since much of the cited work is in Kogyo Kayaku and in Japanese.

Scheiss!!

Ever pondered the merits of mixing up a batch of N5 salt? Polynitrogen chemistry. Yikes. Check out this link (rather large).

May Linkfest

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A friend sent me the link to Wolfram|Alpha  just a while ago. So far it seems to be a bit lean in textbook-style content in the chemistry area. For instance, when you enter “aromatic solvents” into the dialog box, it returns with

Wolfram|Alpha isn’t sure what to do with your input.

But if you type in “toluene”, suddenly it is the CRC and is flush with data. The stated goals of the Wolfram|Alpha developers are-

Wolfram|Alpha’s long-term goal is to make all systematic knowledge immediately computable and accessible to everyone. We aim to collect and curate all objective data; implement every known model, method, and algorithm; and make it possible to compute whatever can be computed about anything. Our goal is to build on the achievements of science and other systematizations of knowledge to provide a single source that can be relied on by everyone for definitive answers to factual queries.

I do not yet know enough about this resource, but it seems to be a data engine rather than a prose engine.

Landscheidt Cycles Research is a site devoted to the Planetary Influence Theory. This theory pertains to the possible gravitational influence of the planets on solar cycles. it is worth a look.

Watts Up With That? is a blog concerned with global climate issues. The blogger and many of the commentors seem to have their facts straight about global climate change. The site is very data intensive.

If you are a scientist or manage scientists, it is worth considering the file drawer effect.

An online NMR predictor can be found at nmrdb. In my experience the splitting and chemical shifts seem to be in the “not too awful” range.

Biohackers

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A recent article in the WSJ solemnly described several amateur biologists who were doing simple molecular biology experiments in their homes. Naturally, this has not escaped the attention of certain authorities and certain deeply conservative establishment news corporations.

What is distressing is the reflexive conclusion that their activity is automatically dangerous and likely to be symptomatic of malevolent intent.  It is common for those in power to look over their ramparts and view the world as a spectrum of threats. And so it is in this case that distrust has arisen and reporters are using the words “weapons of mass destruction” or “ebola virus”. 

Could it not be that some people outside of the heavily in-bred fields of science have a genuine and scholarly interest in molecular biology but no interest in grad school?

The entrance to scientific activity is highly formalized with layers of degree requirements, preferred pedigree, institutional infrastructure, regulatory complications, and a mafia-like oligarchy that disperses the resources and opportunity that is so necessary for buoyancy in science.

How does a creative amateur scientist get to take a jouney of discovery in a field that is institutionally inaccessible to them? And how does an interested individual who is clever enough to conduct experiments deal with a government whose reflex is to see WMD and terrorists behind every lilac bush? There are serious civil liberties problems here that pit the brain stem against the frontal cortex.

It is in the nature of some people to be distrustful and find threats behind every shrub. It has been my observation that people who default into a distrustful posture are very often not trustworthy themselves. The distrustful often invoke slippery slope arguments as rhetorical devices to block their opponents move into new conceptual turf. What the distrustful and paranoid fail to see is that we live every minute of every day on multiple slippery slopes, yet we somehow survive and thrive.

Cresson Gold Mine, Part 3.

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The Cresson Mine in Cripple Creek contains a good deal of fluorite. I was able to casually collect a few samples just lying in the road bed. In the photo below, the rock on the top has the most pronounced blue/purple color indicating CaF2 (fluorite). These specimens are not collectors pieces and are entirely unremarkable other than as indications of fluorite.

Cripple Creek Fluorite Indications (Cresson Mine). Copyright 2009 Gaussling.

Cripple Creek Fluorite Indications (Cresson Mine). Copyright 2009 Gaussling.

The mine business model requires heap leaching as a means of extracting the gold value out of the ore. Given that the ore is peculiar in that it contains gold in the form of gold telluride which cannot be leached out by cyanide, approximately 40 % of the gold remains in the host rock. The cost per toz of gold produced must be kept as low as possible and the way you do that is economy of scale.

The heap sits atop multiple layers of clay barriers and the 14,500 gal per minute of extract that flows out of the heap 24/7 is passed through coconut husk charcoal to trap the gold cyanide and the raffinate is recharged to the desired 100 ppm titer of aq NaCN and pumped back onto the pile. pH adjustment is a constant chore. The crushed rock is mixed with calcuim oxide prior to being dumped on the heap to maintain a high pH.

Building the Heap. Cripple Creek Cresson Mine. Copyright 2009 Gaussling.

Building the Heap. Cripple Creek Cresson Mine. Copyright 2009 Gaussling.

Cresson Gold Mine, Part 2.

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We collected samples of the lamprophyre in the bottom of the pit. The formation appeared whitish green in on the weathered surface owing to oxidation. However, if a fresh surface was exposed, the rock was composed of sugary dark xtals with the occasional biotite phenocryst.

Outlined Lamprophyre at bottom of Cresson open pit mine

Outlined Lamprophyre at bottom of Cresson open pit mine. Copyright 2009 Gaussling.

Cresson Mine Lamprophyre Close-up

Cresson Mine Lamprophyre Close-up. Copyright 2009 Gaussling.

Mafic or ultramafic rocks are low in silicates and enriched in Fe and Mg oxides. The lamprophyre above is mafic in composition with a sugary xtal matrix with biotite and other phenocrysts.

Breccia from Cripple Creek Diatreme

Breccia from Cripple Creek Diatreme. Copyright 2009 Gaussling.

The breccia above is characteristic of the Cripple Creek diatreme. Relatively rounded clasts populate the mass of the aggregate, indicating that the clasts were rounded by some process prior to deposition.

The gold is generally too dispersed to see, however, you can see pyrite with a hand lense in many of the samples. Pyrite often accompanies gold.

A Massive Au/AuTe Deposit

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Th’ Gaussling attended a geology seminar thursday evening at the Colorado School of Mines. It was given by the chief geologist at the Cripple Creek & Victor gold mine (now AngloGold Ashanti) and was concerned with 3-D modeling of the volcanic formation that forms the center of the deposit.

What is unusual about the CC&V mine is the extent to which tellurium is present. There are a dozen or more tellurium minerals and many of them are present in the ore body. The CC&V load was discovered relatively late- about 1891. Due to the extensive fraction of AuTe and AuAgTe minerals, the presence of the ore body was not detected by placer prospecting. 

Prospectors panning for gold in local streams had no way of knowing that extensive gold was present because AuTe(Ag) minerals do not have a gold-like appearance.  Legend has it that it was discovered by a drunken cowboy who noticed some native gold in an outcropping in the area and took a sample down for assay. As I have mentioned before, the Cripple Creek district has produced about half of all the g0ld to come out of Colorado.

What is key to the formation is the fact that it has zones of extensively altered volcanic rock disturbed both mechanically in the form of fractures and faulting, and chemically in the form of its potassic-alkali nature. The formation has strongly brecciated zones and is desribed as “vuggy”, meaning that there are extensive voids. Native gold and gold telluride mineralization can be found on the surfaces of the vugs. The mineralization was deposited by hydrothermal streams extracting Au and Te from unknown source rock.

Presently the operation is surface mining which feeds to a cyanide leach field for gold extraction. The surface pit mine is working downward, digging through the extensive network of mineshafts. In the early days at Cripple Creek the mining was limited to underground activity. Miners would follow the extensive subsurface network of gold-rich veins in whatever direction they might go. The result is a very complex and extensive matrix of tunnels and shafts that extend downward to as low as 3000 ft. In the early days, the economics of subsurface vein mining were attractive enough to sustain the operation. Today, the economy of scale dominates and pit mining with heap leaching of the lower grade ore is what sustains the operation.

The gold is recovered by a cyanide leach field that is 800 ft thick in places. This method produces ca 300,000 toz/yr. The process does not recover Au from AuTe. It is left untouched in the leach heap and constitutes ca 1/3 of the total gold present.

Curiously, during the many eruption cycles in the distant past (~32 ma), debris from the surface has washed back deep into the formation. Bits of woody debris have been recovered within cementitious rock hundreds of feet below the surface. The CC&V geologist showed a core sample with a wood fragment imbedded within it. For a time reference, the current episode of Rocky Mountains (the Laramide Orogeny) began ~65 ma.

Chemist Gaussling will blend in with a group of geologists tomorrow morning and take an extensive geology tour of the mine site. Hopefully, there will be pictures to share. We’ll be going up to ~10,000 ft, so it will be chilly.

LC Dreamin’

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When I get to work this morning I’ll be greeted with a brand spankin’ new Agilent 1200 HPLC sitting on the bench in my lab. It has a diode array detector (no flippin’ MS this time). Pretty sweet.  Gosh, early 1990’s LC capability- already!

It is interesting how the installer assumed I’d be doing reverse phase work. Must be what most of the weenies in pharma are using. Carbon-heteroatom-carbon-heteroatom-carbon-heteroatom-carbon=heteroatom-carbon-heteroatom- … maleate.