Thursday, August 31, 2023

MolDx Summarizes 4600 word LCD in 600 words.

Chat GPT summarizes RA LCD (4600 words) in 600 words.

Main Blog

https://www.discoveriesinhealthpolicy.com/2023/08/busy-day-at-moldx-new-draft-lcd-for.html

Summary of RA LCD L39427:


Certainly, I've received all three parts of the document. I'll provide a detailed summary of the content you've shared.

Summary:

The document addresses the use of predictive biomarker tests for therapy selection in Rheumatoid Arthritis (RA), discussing the limitations, evidence, and potential utility of such tests. The primary focus is on a specific test known as the molecular signature response classifier (MSRC), developed by Scipher Medicine, which aims to predict non-response (NR) to Tumor Necrosis Factor-alpha inhibitors (TNFis), a common class of biologic therapies for RA.

  1. Background and Context: The document highlights the challenges of treating RA, an inflammatory autoimmune disease that can lead to significant morbidity and mortality if inadequately managed. Traditional treatments include conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but a substantial portion of patients do not respond adequately to these therapies. Hence, biologic and targeted synthetic DMARDs (b/tDMARDs) like TNFis are often employed.

  2. Coverage Indications and Limitations: The coverage policy discussed pertains to molecular biomarker tests designed to guide targeted therapy selection in RA. The criteria for coverage include confirmed diagnosis, prior therapy failure, absence of prior biologic therapy, predictive ability of the test for targeted therapy response, and validation according to specific criteria.

  3. Discussion of Predictive Biomarker Tests: The document reviews various predictive biomarker tests that have been proposed to aid in predicting response or non-response to specific classes of drugs in RA treatment. One test, the MSRC, developed by Scipher Medicine, is focused on predicting NR to TNFis. This test combines genetic markers, gene transcripts, laboratory tests, and clinical parameters to generate a predictive score. Studies have evaluated the accuracy and efficacy of the test in guiding therapy decisions.

  4. Study Findings and Limitations: Several studies have explored the effectiveness of predictive biomarker tests. The MSRC, in particular, demonstrated potential in identifying patients who are likely to be non-responders to TNFis. The studies suggest that the test's predictive accuracy is superior to individual clinical features, providing a valuable tool to guide treatment decisions.

  5. Challenges and Considerations: Despite the potential benefits, there are challenges associated with the adoption of predictive biomarker tests. The document discusses the limitations of available evidence, including the heterogeneity of RA and treatment response, the lack of external validation for some tests, and the influence of various clinical and non-clinical factors on treatment decisions.

  6. Clinical Application and Future Implications: The document acknowledges the potential utility of predictive biomarker tests in informing targeted therapy decisions for RA. However, it also emphasizes that the current tests, including the MSRC, have limitations in terms of predicting non-response to specific classes of drugs, such as TNFis. The document highlights the need for further research and the development of more accurate tests that can better predict treatment responses in a broader range of RA patients.

  7. Coverage Policy and Recommendations: The coverage policy outlined in the document suggests that, despite the limitations of the current predictive biomarker tests, there is a pragmatic value in their limited use for a specific subset of RA patients who are likely to be non-responders to TNFis. The policy also underscores the importance of evidence-based testing and treatment decisions.

  8. Monitoring and Future Changes: The document concludes by stating that the contractor will continue to monitor the evidence and may modify coverage policies based on new information and evolving recommendations from the medical community.

In summary, the document extensively explores the use of predictive biomarker tests, primarily focusing on the MSRC, in guiding targeted therapy selection for RA patients. It discusses the challenges, evidence, and implications of such tests, highlighting both their potential benefits and limitations. The document emphasizes the need for continued research to develop more accurate predictive biomarker tests that can enhance treatment outcomes for a broader range of RA patients.

MolDx Changes Its Mind (R.A. Tests)

 MolDx converted a draft non coverage LCD on RA GEP tests, to a limited coverage policy.

Blog here:

https://www.discoveriesinhealthpolicy.com/2023/08/busy-day-at-moldx-new-draft-lcd-for.html

The key decision rationale is in the Q&A document A59519 here:

During the comment period, we received many letters supporting a coverage policy for Molecular Biomarker Testing to Guide Targeted Therapy Selection in Rheumatoid Arthritis. 

  • Of note, we have acknowledged the need for testing to help physicians and patients avoid a trial-and-error based approach to care. 
  • However, we have also acknowledged the limitations of the currently available clinical and laboratory tools to support this effort, as noted in the draft policy that evaluated the data available in the published literature. 
    • For example, the molecular biomarker tests had not adequately demonstrated that they can reliably identify responders and/or non-responders to a particular class of therapies beyond what is already known at baseline (i.e. uninformed by the test), given that 
    • (a) the overall prevalence of non-response to TNF inhibitors (TNFi), a mainstay of therapy, is so high in this population (~60-70%) and 
    • (b) multiple clinical and laboratory data also provide some information regarding the likelihood of response to these therapies. 
  • Since then, additional data/newer publications addressing these issues have been published and were provided during the comment period. The policy was therefore modified as an outgrowth of the comments received.

We appreciate the many comments received in support of a coverage policy. We agree that despite the many limitations of predictive biomarker tests, a review of the evidence supports their limited use given their demonstrated validity and utility. 

  • Specifically, when a non-response (NR) signature is obtained by the molecular signature response classifier (MSRC), nearly 90% of those patients will prove to not clinically respond to TNFi therapies using multiple validated disease response criteria including the ACR50 and CDAI. 
  • For these patients, a change in management would ultimately serve to avoid time on an unnecessary therapy and shorten the time to an appropriate therapy.

However, we also highlight some important points about the evidence regarding these tests to-date: 

1. They have only demonstrated their utility in a subset of the RA population (only half of the TNFi non-responders), 

2. They are only informative about one particular class of therapies (TNFis), 

3. The use of this testing does not guarantee improved disease activity and/or remission outcomes (because many of these patients will also not initially respond to the alternate therapies) and 

4. It is not appropriate that patients continue classes of therapy that they have already failed due to payor preference and/or lack of consideration of national guidelines (that support switching over cycling). 

As a result, it is likely that future tests will add substantially more benefit than the current services offered and reviewed by this contractor, and we will continue to monitor new evidence as it becomes available.


###
AI CORNER
We ask ChatGPT 3.5 about the change of heart shown above.

Regarding specifically the R.A. or rheumatoid arthritis test, MolDx took the unusual (but not impossible) step of converting a draft non coverage policy to a final coverage policy.  They explained their rational in section that we will paste below.   Discuss whether the change of mind was difficult for the author, and what his ongoing reservations are.

The decision by MolDx to convert a draft non-coverage policy for the Molecular Biomarker Testing to Guide Targeted Therapy Selection in Rheumatoid Arthritis to a final coverage policy appears to have been a nuanced and considered process. The rationale provided suggests that the change of mind was driven by a combination of factors, including the receipt of numerous letters supporting coverage during the comment period and the emergence of additional data and newer publications addressing the limitations raised in the initial draft policy.

The change of mind may not have been easy for the author or the organization, as it required reevaluating the evidence, acknowledging new information, and potentially reassessing their initial reservations. The author's ongoing reservations are outlined in the provided section. These reservations seem to revolve around the following points:

  • Subset of RA Population: The author notes that the molecular biomarker tests have demonstrated utility only in a subset of the rheumatoid arthritis (RA) population, specifically among non-responders to TNF inhibitors (TNFis). This suggests that the tests might not be universally applicable to all RA patients.
  • Specific Class of Therapies: The tests are informative about a particular class of therapies, namely TNFis. This implies that the coverage policy change is not a blanket endorsement for all treatment options but is focused on a specific subset of treatments.
  • Uncertain Improvement in Outcomes: The author emphasizes that while the tests can help identify patients who are unlikely to respond to TNFis, their use does not guarantee improved disease activity or remission outcomes. This underscores the complexities of RA treatment and the potential limitations of relying solely on these tests for decision-making.
  • Consideration of National Guidelines: The author points out that patients should not continue therapies they have already failed due to payer preference or the lack of consideration of national guidelines. This raises a broader issue of treatment continuity and adherence to established medical guidelines.
  • Future Developments: The author acknowledges the potential for future tests to offer greater benefits than the current ones. This implies that the current coverage policy is based on the available evidence and may evolve as more data become available.

In conclusion, the change from a draft non-coverage policy to a final coverage policy for Molecular Biomarker Testing to Guide Targeted Therapy Selection in Rheumatoid Arthritis suggests a careful consideration of the evidence and feedback received during the comment period. The author's ongoing reservations highlight the complexities of implementing such tests in clinical practice and the need for continuous monitoring of emerging evidence to ensure the best possible patient outcomes.


ChatGPT 3.5 rewrites my MolDx LCD's Blog

 Rewritten by Chat GPT. Trimmed from 1000 words to 650.

https://www.discoveriesinhealthpolicy.com/2023/08/busy-day-at-moldx-new-draft-lcd-for.html


On Thursday, August 31, 2023, MOLDX, a medical diagnostics organization, had a busy day announcing new draft and final Local Coverage Determinations (LCDs) related to various genetic and molecular tests for different medical conditions.

New Draft LCDs:

  1. Advanced Prostate: MOLDX introduced a new draft LCD related to gene expression profile (GEP) tests for decision-making in castration-resistant and metastatic prostate cancers. This LCD is a revised version based on a letter from Dr. Davincioni of Decipher/Veracyte from February 2022. Unlike previous versions that focused on early diagnosis and management, this LCD is intended for patients facing multiple therapy options of varying severity. It aims to help physicians make informed treatment choices. The LCD doesn't specify covered or non-covered tests, but it is associated with billing article DA59462, listing 81479 as a potentially covered code. Notably, the Veracyte Decipher collaboration with Duke University was highlighted in the field.

  2. Lung Nodules: Another draft LCD, DL39654, discusses molecular biomarkers for risk stratification of indeterminate pulmonary nodules following bronchoscopy. While it appears to be related to tests like the Veracyte Percepta test, it is framed for patients post-bronchoscopy. The LCD differentiates between "first generation" and "second generation" Percepta tests. The billing article DA59476 provides complementary information and lists 81479 as a possible billing code. Additionally, an LCD for the "XL2" test from Biodesix is mentioned for cases of incidental lung nodules.

  3. Thyroid Nodules: LCD DL39646 addresses risk stratification for thyroid nodules based on a letter from Veracyte (Dr. Gerrard) from January 2022. It applies to patients with Bethesda III or IV indeterminate nodules or Bethesda V nodules where molecular testing can aid in decision-making. The LCD emphasizes the importance of avoiding unnecessary thyroid surgeries and highlights the potential benefits of molecular tests in guiding clinical decisions. A billing article (DA59470) provides information on covered codes, including 81479 and 81546 (Veracyte GSC Genomic Sequencing Classifier).

New Final LCD:

MOLDX released a new final LCD concerning Rheumatoid Arthritis (RA). LCD L39424 was based on a letter from SCIPHER, discussing the PRISM-RA test. The original draft in October 2022 stated that molecular biomarker tests for guiding therapy selection in RA were non-covered. However, the final LCD now offers limited coverage based on new evidence and specific criteria. Patients with a history of failure or contraindication to first-line DMARD treatments considering alternate therapies (TNF, JAK, etc.) are eligible for coverage. The LCD references the appropriate validation and design of the test. The billing article (A59529) mentions 81599 as a possible billing code. A detailed "response to comments" document (A59519) accompanies this change in coverage status.

Coordination and Comment:

This batch of draft and final LCDs demonstrated better coordination in terms of posting, likely to speed up the finalization of drafts. The draft LCDs are open for comments from August 31 to October 14.

Convergent Evolution of LCD Text:

LCDs for indeterminate nodules (such as those in the lung and thyroid) show a trend toward using similar language for coverage and performance rules. These rules often emphasize that tests must be appropriately designed for the target population.

Challenges for Academics and Publications:

Despite efforts to document and publish payor policies, the lack of specific coverage details in LCDs or articles poses challenges for policy experts. While databases like DEX can provide some information, they often lack coverage dates and historical records, limiting the ability of academics and consultants to analyze coverage issues systematically.

PAMA Impact:

The widespread use of "unlisted codes" for billing for genetic and molecular tests can potentially bypass the pricing system established by the CMS and Congress, potentially affecting the effectiveness of the PAMA (Protecting Access to Medicare Act) pricing system. This is particularly significant as genomics plays an increasing role in laboratory spending.

Overall, this day marked significant activity in the realm of genetic and molecular diagnostic testing policies, reflecting ongoing developments in medical technology and healthcare coverage.

Wednesday, August 30, 2023

Air Conditioning Funny Sounds: Chat GPT4 Can Discuss

 

We live in Los Angeles, and our air conditioner is on the roof of our house. 

It has been working normally this summer, when it runs is it typically on for 10 minutes and off for 10 minutes. I take this is normal. 

Tonight it seems like it’s going on and off every 30 seconds. What could this mean?

ChatGPT

If your air conditioner is cycling on and off every 30 seconds, it's not operating normally. This rapid cycling is often called "short cycling," and it can be caused by several issues:

1.     Thermostat Issues: If your thermostat is malfunctioning or is placed in a location where it's getting rapid temperature changes (like near a vent or in direct sunlight), it might cause the system to short cycle.

2.     Oversized AC Unit: If your AC unit is too large for the space it's cooling, it might cool the area too quickly and shut off. However, since you mentioned it has been working normally this summer, it's less likely to be the cause in this case.

3.     Low Refrigerant: If the refrigerant levels are too low, the AC might not be able to sustain a cooling cycle, causing it to turn off prematurely.

4.     Dirty or Clogged Filter: A dirty or clogged filter can restrict airflow, causing the unit to shut down quickly to prevent a freeze-up.

5.     Dirty or Iced Evaporator Coils: Similar to a dirty filter, if the coils are dirty or iced over, they can't transfer heat effectively, leading to short cycling.

6.     Electrical Issues: Problems with wiring, corroded terminals, or other electrical components can cause the system to shut down unexpectedly.

7.     Safety or Pressure Switches: Modern AC units have various safety and pressure switches to prevent damage. If one of these switches is tripped due to some underlying issue, it could cause short cycling.

8.     Compressor Issues: The compressor is the heart of the AC system. If it's malfunctioning, it can result in short cycling.

It's essential to address short cycling as soon as possible because it can lead to increased wear on the system, higher electricity bills, and reduced comfort in your home. I would recommend contacting a licensed HVAC technician to diagnose and fix the problem.

Top of Form

 

Henry Adams vs Henry Clay: ChatGPT Explains the Difference

 

Please explain Henry Adams and Henry Clay, and the difference between them

ChatGPT

Certainly!

Henry Adams (1838-1918)

  1. Occupation: Historian, journalist, and novelist.
  2. Noteworthy Works: "The Education of Henry Adams" - an autobiography that traced his own intellectual development and is considered a classic in American literature.
  3. Background: He was a member of the Adams political family. He was the great-grandson of John Adams (2nd U.S. President) and grandson of John Quincy Adams (6th U.S. President).

Henry Clay (1777-1852)

  1. Occupation: Politician and statesman.
  2. Political Roles: He served as Speaker of the House of Representatives, U.S. Senator from Kentucky, and was the Secretary of State under John Quincy Adams.
  3. Major Achievements: He was known as the "Great Compromiser" for his role in negotiating compromises in the U.S. Senate, most notably the Missouri Compromise and the Compromise of 1850, which aimed to maintain a balance between slave and free states.
  4. Presidential Runs: Clay ran for president multiple times but never won.

Difference Between Them:

  • Time Period: While their lifetimes overlapped, Henry Clay's prominence was in the early 19th century, while Henry Adams' main contributions were towards the end of the 19th and early 20th centuries.
  • Occupation: Clay was primarily known for his political career, while Adams was known for his work as a historian and writer.
  • Family Background: Adams was from the distinguished Adams family, which produced two U.S. presidents, while Clay, though from a prominent political family in Kentucky, did not have presidential lineage.

I hope this provides a clear distinction between the two!

User

Both first names are Henry, which is confusing.

ChatGPT

I understand the confusion! Historical figures with the same first name can sometimes be hard to keep apart, especially when they both made significant contributions in their respective fields.

To simplify:

Henry Adams

  • Historian, journalist, novelist.
  • Known for his autobiography, "The Education of Henry Adams."
  • Part of the Adams political family (related to two U.S. Presidents).

Henry Clay

  • Politician and statesman.
  • Known as the "Great Compromiser" for his role in key political compromises.
  • Held positions such as Speaker of the House and Secretary of State.

Remembering the key roles they played and their last names can help distinguish them. Adams was more in the literary and historical realm, while Clay was deeply embedded in politics.

User

Focusing on Henry Adams, what works is he actually known for, period. I'm fairly well educated, but I could not name one, period.

ChatGPT

Of course! Henry Adams is best known for his historical writings and his autobiography. Here are some of his works:

  1. "The Education of Henry Adams" (1907) – This is his most famous work, an autobiography that's less about his personal life and more about his intellectual development. It reflects on the rapid changes in the world from the 19th to the early 20th century.
  2. "Mont Saint Michel and Chartres" (1904) – A study of medieval culture, presenting the history of the 11th, 12th, and 13th-century France through the architecture, sculpture, and stained glass of cathedrals, especially Mont Saint Michel and Chartres.
  3. "History of the United States of America (1801–1817)" (9 volumes, 1889–1891) – This work covers the presidencies of Jefferson and Madison and is still cited by historians for its thoroughness and accuracy.
  4. "The Degradation of the Democratic Dogma" (1919, posthumously published) – A collection of essays.
  5. "Esther" (1884) – A novel.

While "The Education of Henry Adams" is his most widely read and acclaimed work, earning him a posthumous Pulitzer Prize, his other writings also had a significant influence on historical and intellectual thought. However, to your point, he might not be as widely recognized in popular culture as some other historical figures.

User

Regarding point number four, what are some of the topics of his essays.

ChatGPT

"The Degradation of the Democratic Dogma" is a collection of Henry Adams' essays, and its main theme revolves around his thoughts on the evolution of democracy, the role of education, and his theories on history and societal change. Here are some topics and themes explored in his essays:

  1. The Rule of Phase Applied to History: Adams presents his theory about history following a set path or phases, somewhat drawing from the Second Law of Thermodynamics. He postulates that societies, like physical systems, might move from states of order to disorder.
  2. A Letter to American Teachers of History (1910): This essay expresses his views on the role of education and the responsibilities of teachers in shaping the nation's intellectual trajectory. He emphasizes the importance of understanding history in a rapidly changing world.
  3. The Tendency of History: Explores the patterns and movements of history, especially in relation to democratic societies.
  4. The Decay of England: Examines the decline of British power and its implications.

These essays, combined, showcase Adams' often pessimistic view on the trajectory of democracy and society, especially in the face of rapid technological and societal changes. He questioned traditional notions of progress and believed that society might be heading towards increased complexity and potential chaos.

User

But he lived through great changes in standard of living through technology an increase in the gross domestic product. He would remember the world of 1850 but lived in the world of 1910, which is a mind-boggling technological difference. He found this depressing?

ChatGPT

You're absolutely right in noting the vast technological and societal changes that occurred during Henry Adams' lifetime. And yes, while many people viewed these changes as signs of progress and celebrated the advancements, Adams had a more nuanced and often ambivalent perspective.

Henry Adams recognized the immense progress and the benefits that came with it. However, he was also deeply introspective and often pondered the broader implications of such rapid change on society, culture, and the human psyche.

  1. Complexity and Loss of Individual Control: Adams noted that as society became more complex, individuals had less control over the forces that shaped their lives. The rise of vast industrial systems, large corporations, and powerful governments meant that individual agency was diminished.
  2. Educational Challenges: In "The Education of Henry Adams", he discussed the inadequacy of traditional education in preparing individuals for the modern world. He felt that educational systems hadn't kept pace with the rapid changes in society.
  3. Historical Cycles: Drawing inspiration from his understanding of the Second Law of Thermodynamics, Adams theorized that civilizations might follow a trajectory of rise and fall. Just as energy dissipates in a closed system, he pondered if societal energy and dynamism might similarly dissipate over time.
  4. Cultural and Moral Implications: Adams also questioned the cultural and moral implications of rapid technological change. For instance, the advancements in warfare technology made conflicts deadlier, and the pace of change sometimes outstripped society's moral compass.

It's important to understand that Adams' reflections weren't just a reaction to the negative aspects of change. Instead, they were a deep philosophical inquiry into the nature of progress, the role of individuals in a rapidly changing society, and the challenges and uncertainties brought about by unprecedented advancements. He wasn't simply "depressed" by change but was critically analyzing its broader implications.

 ####

Sadly, his wife committed suicide.

ChatGPT

Yes, that's true. The suicide of Clover Hooper Adams, Henry Adams' wife, in 1885 was a profound tragedy in his life. Marian "Clover" Hooper Adams, a talented photographer, took her own life by ingesting potassium cyanide, a chemical she used in her photography work.

Henry Adams was deeply affected by her death, and his grief was palpable. He did not write explicitly about this traumatic event in his autobiography, "The Education of Henry Adams," but its impact is evident in the somber tone of certain sections.

In her memory, he commissioned the famous sculptor Augustus Saint-Gaudens to create a memorial for her grave. The result, known as the Adams Memorial or "Grief" monument, is a haunting and powerful sculpture located in Rock Creek Cemetery in Washington, D.C. The statue captures the profound sense of sorrow and loss that Adams felt, and it remains an iconic representation of grief.

User

Was ingestion of potassium cyanide by photographers in this way, common?

ChatGPT

2 / 2

Ingesting potassium cyanide was not a common method of suicide among photographers. However, potassium cyanide was a chemical used in the photography process, particularly in the development of photographs during the 19th century. It was employed as a fixing agent to stabilize and remove unreacted silver from the photographic plate, making the image permanent.

Given its presence in photographic studios, it would have been accessible to photographers and those involved in the photographic process. Potassium cyanide is highly toxic, and even small amounts can be lethal if ingested.

Clover Hooper Adams' use of potassium cyanide for her suicide can be understood in the context of her access to the chemical due to her work in photography, rather than a trend or commonality among photographers. It's important to approach the topic with sensitivity and recognize that her reasons for taking her own life would have been deeply personal and complex.

User

Potassium cyanide must have been replaced by something, for removing the free silver.

ChatGPT

Yes, indeed. Potassium cyanide was used in the earlier days of photography as a fixing agent, but due to its high toxicity, it was replaced by safer alternatives.

The most common replacement for potassium cyanide in the photographic process was sodium thiosulfate, which came to be commonly known as "hypo." Sodium thiosulfate is much less toxic than potassium cyanide and effectively removes unreacted silver from photographic plates and films, making the image permanent.

As photography evolved and newer methods and materials were introduced, the need for chemicals like potassium cyanide and even sodium thiosulfate reduced, especially with the advent of digital photography. However, in traditional film processing, sodium thiosulfate remains a standard fixing agent.

User

Doesn't "thio" mean "sulfate"?

ChatGPT

You're close, but there's a distinction to be made:

  • "Thio-" typically indicates the replacement of an oxygen atom by a sulfur atom in certain compounds.
  • "Sulfate" refers to the anion or ester containing the anionic form of sulfuric acid, ��42−SO42−.

So, in the compound sodium thiosulfate, "thio" indicates that one of the oxygen atoms in the sulfate ion has been replaced by sulfur. The chemical formula for sodium thiosulfate is ��223Na2S2O3, with the 232−S2O32− ion representing the thiosulfate anion.

To summarize, while "thio-" involves sulfur, it specifically denotes the substitution of oxygen with sulfur, and doesn't mean "sulfate" by itself.

User

S1O4 becomes S2O3.

ChatGPT

Yes, you're correct in noting the difference between the two ions.

��42−SO42− is the formula for the sulfate ion.

232−S2O32− is the formula for the thiosulfate ion.

In the thiosulfate ion, one of the oxygens in sulfate is replaced by a sulfur atom, leading to the 232−S2O32− structure. This is why it's named "thiosulfate," with "thio-" indicating the presence of the additional sulfur atom.

User

Is there also an S3O2 form?

ChatGPT

No, there isn't an 322−S3O22− ion. The thiosulfate ion 232−S2O32− is the well-known species with a structure derived from the sulfate ion by replacing an oxygen with a sulfur atom.

Chemistry, especially inorganic chemistry, is governed by a complex interplay of factors such as electron configurations, bond strengths, bond angles, and steric effects. Not all combinations of atoms result in stable compounds, and 322−S3O22− is not among the known stable ions.

That said, the realm of sulfur-oxygen compounds is vast and includes various combinations, but 322−S3O22− is not one of them to the best of current knowledge (as of 2021).

User

Write a vignette about a grad student who is fascinated by the transition from S1O4 to S2O3 and sees it as a great challenge - his Moby Dick, his beckoning Anapurna - to create S3O2.

ChatGPT

The Quest for S₃O₂

In the heart of the university's chemistry department, surrounded by glassware and the hum of machines, Julian was on the cusp of an obsession. To most, the world of inorganic chemistry was a labyrinth of complex reactions and myriad compounds. But to Julian, a diligent grad student, it was a realm of endless possibility. His recent dive into sulfur-oxygen compounds, especially the transition from 14S1O4 to 23S2O3, had ignited a spark in him.

Julian saw in 32S3O2 not just a mere chemical compound, but a metaphor for his own aspirations. It represented the unknown, the unconquered—a challenge that beckoned him like the mythical siren's call. He often likened his pursuit to Captain Ahab’s chase of the elusive Moby Dick or a mountaineer's relentless ambition to summit the treacherous Annapurna.

The corridors of the department would often echo with Julian's contemplative murmurs. "If 14S1O4 can become 23S2O3," he would muse, "then why not 32S3O2? Why does it resist formation? What's the secret behind its instability?"

His peers admired his passion but couldn’t fathom his obsession. "Why chase a ghost, Julian?" they would ask, to which he'd reply, "Because, my friends, in that ghost lies the future of inorganic chemistry. There’s an elegance in the unseen, a beauty in the unachieved."

Months turned into years. Julian's workbench became littered with failed experiments and scribbled notes. But every setback, every explosion or unwanted byproduct, only fueled his determination. The compound became a puzzle, with each failed attempt a clue bringing him closer to the answer.

One late winter evening, with snow blanketing the world outside and the lab's lights casting long, thoughtful shadows, Julian felt he was on the brink of a breakthrough. A new approach, a slight alteration in temperature and pressure, a dash of a catalyst—he could feel the pieces falling into place.

And as dawn broke, casting the first golden rays of the sun on the frosty windows, Julian held up a vial, its contents shimmering in the morning light. Whether he had truly created 32S3O2 or found another piece of the puzzle was yet to be seen. But in that moment, it wasn’t just about the compound; it was about the journey, the relentless pursuit of knowledge, and the passion that drives one to chase their own personal Moby Dick.

Top of Form

 Remarkably there is a REDDIT short thread on S3O2 and it links to a German 1982 paper (apparently it can be just momentarily stabilized with molybdenum).   I am including the links here just for my own future reference in this dialog.   https://www.reddit.com/r/chemistry/comments/hc2jwj/what_about_dithiosulfate_s3o22/?onetap_auto=true       and   https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.198207961   and  Fixation of the Dithiosulfate Ion S3O2; Preparation, Crystal Structure, and ESCA Spectrum of (PPh4)2[(S2)OMoS2MoO(S3O2)]   Prof. Dr. Achim Müller, Uta Reinsch-Vogell, Erich Krickemeyer, Dr. Hartmut Bögge.


That's fascinating! The world of inorganic chemistry often brings about surprises, and the stabilization of unstable or previously unobserved species with transition metals (like molybdenum) is a testament to the intricate and multifaceted nature of chemical bonding.


The mention of molybdenum acting as a stabilizing agent for the 

3

2

2

3

 O 

2

2−

  ion shows how inorganic chemistry can push the boundaries of what's considered possible. Transition metals, with their ability to form multiple bonds and engage in a variety of coordination environments, have a history of stabilizing otherwise elusive species.


This discovery highlights the importance of continuous exploration in chemistry. While theoretical predictions and chemical intuition can guide us, empirical experimentation often reveals the unexpected. Your find on Reddit and the linked paper emphasizes the fact that there's always more to learn, and chemistry never ceases to surprise.


Thank you for sharing this interesting tidbit. It's a great reminder of the ever-evolving nature of scientific knowledge.





User

Can you interpret the original chemistry paper?   Fixation of the Dithiosulfate Ion S30f-; 

Preparation, Crystal Structure, and ESCA Spectrum 

of (PPh~)zI(Sz)OMoSzMoO(S,Oz)l 

By Achim Miiller*, Uta Reinsch- VogeN, Erich Krickemeyer. 

and Hartmut Bogge 

Previous attempts to isolate S30:- as the salt, or to sta- 

bilize it by complexation, have not met with success. We 

have now been able to fix by complexation the SiO; 

formed on oxidation of St- ligands in a metal complex 

with oxygen. Such reactions are relevant to the metabolism 

of phototrophic microorganisms which oxidize So or S’- 

and are effective in the sulfur cycle[’].The reaction is, how- 

ever, also of interest for an understanding of the oxidation 

of simple ‘‘sulfur species”. 

When a solution of (PPh4),MoOS3 and sulfur in acetoni- 

trile [Reaction (a)] or of (PPh4)2MoS4i n dimethylformam- 

ide [Reaction (b)] is exposed to oxygen, gradual formation 

of brown, crystalline (PPh4)2[(Sz)OMoSzMoO(S,0,)] 1 i s 

observed. As shown by an X-ray structure analysis [Cc, 

a =2082.4(9), b = 1364.6(8), c = 1885.7(8) pm, 

p= 108.98(3)”, V = 5066.9 x 106 pm3, Z=4; R =0.062 for 

4124 reflections] an S i - as well as the bidentate dithiosul- fate ligand &Of- are coordinated to the known central 

OMoS,MoO unit“] in the complex anion of 1 (cf. Fig. I 

with atomic distances). As expected, the average SS dis- 

tance in the dithiosulfate ligand is longer, the average SO 

distance somewhat shorter than in the “isolated” S20: - 

2 (ca. 200 and 146 pmiIh1, respectively). The OSS angles 

[110.5(7), 110.2(6), I10.6(6), 112.1(6)”] have values about 

the same as in the regular tetrahedron or as in 2, whereas 

the SSS angle [96.2(2)”] is expectedly smaller and the OSO 

angle [ I 15.6(9)”] correspondingly larger than the OSS bond 

angles. Asymmetrically coordinated complexes containing 

the OMoS2Mo0 moiety are already known.   method: besides an S-2p signal at 162.7 eV (for a total of 

six “sulfidic” sulfur atoms in 1, i.e. two from the dithio- 

sulfate and four others) a signal is observed at 168.6 eV 

(for s+”‘) 


in the intensity ratio 6 : 1; ~ ? ~ ( M o - s da~p/p~e)a rs 

at 230.3 eV (all values relative to &,(C-lsl/2)=285.0 eV). 

The ligand also shows characteristic IR bands in the solid 

state spectrum (KBr pellet) of 1 : vaS(SO2)= 


1255, 

v,,(SS2)/6(S02)=598, 557 c m - ’ ; v(Mo0)=955 cm-’. 

Very little is known about the oxidation of S:- ligands 

(x= 1-5). In the present case, S30:- could be schemati- 

cally formed in reaction (a) (without considering redox 

processesi2“];i . e. reduction of Mo”’) according to 

0. 


(Mo(S’-)J 5( Mo(S:-)] (Mo(S:-)J - (Mo(S,Oi-)} 

(by activation of S:- and stabilization of S30:- on Mo), 

since the complex [(S,)OMOS~MOO(S,)]~- 


is formed (to- 

gether with [OMo(S,),J2-) in the same reaction-but under 

Nz[*”]. In reaction (b), MoSj- could furnish the fragment 

(Mo(S:-)), which should react further according to (a)“]. 

In the sulfur cycle, which is important for the biosphere 

and our ecosystem, microorganisms are effective which re- 

duce SO:- (by assimilatory reduction but also in “sulfate 

respiration”), or which oxidize reduced species such as 

S’- or So, like the phototrophic prokaryotes Chromatia- 

ceae and Chlorobiaceae. Possibly, not only sulfur-rich an- 

ions such as S 2 0 < - 1 ’a1r e formed in the photosynthetic 

processes, but also previously undetected species such as 

S30:- (e. 


g. as intermediates). 


Received: May 19, 1982 [Z 40b IE] 

German version: Angew. Chem. 94 (1982) 784 

ChatGPT

Certainly! This paper describes a complex inorganic chemistry study, but let's break it down into its key points:


Objective and Background:


The team attempted to isolate or stabilize the 

3

2

3

 O 

2−

  ion, which had been elusive in prior attempts. They were driven by the fact that understanding the reactions involving these sulfur species could have implications in understanding the metabolism of phototrophic microorganisms, which play roles in the sulfur cycle.

These microorganisms are known to oxidize 

0

0

  or 

2

2−

 , and understanding these reactions can also help in grasping the oxidation of simple sulfur species.

Experiments:


They found that when a solution of 

(

4

)

2

3

(PPh 

4

 ) 

2

 MoOS 

3

  and sulfur in acetonitrile or 

(

4

)

2

4

(PPh 

4

 ) 

2

 MoS 

4

  in dimethylformamide is exposed to oxygen, a brown crystalline compound is formed: 

(

4

)

2

[

(

2

)

2

(

3

2

)

]

(PPh 

4

 ) 

2

 [(S 

2

 )OMoS 

2

 MoO(S 

3

 O 

2

 )].

An X-ray structure analysis of the compound showed an 

2

2−

  and the sought-after 

3

2

3

 O 

2−

  ion coordinated to a central 

2

OMoS 

2

 MoO unit in the complex anion. There were comparisons of bond lengths and angles to expected and known values.

Characterization:


The Electron Spectroscopy for Chemical Analysis (ESCA) spectrum of the compound displayed signals that confirmed the presence of the sulfur species in the complex.

The infrared (IR) spectrum of the complex also showed characteristic bands that corresponded to the vibrations of specific bonds, further confirming the compound's structure.

Discussion:


The paper discusses possible reactions that might lead to the formation of the 

3

2

3

 O 

2−

  ion. They propose possible mechanisms for the ion's formation and stabilization on molybdenum.

They note that in the sulfur cycle, essential for the biosphere, specific microorganisms reduce or oxidize sulfur species. Some of these reactions might lead to the formation of 

3

2

3

 O 

2−

  or other related species, especially during photosynthetic processes. This information is crucial as it ties back to the relevance of their research in a broader ecological and biological context.

Conclusion:


The researchers successfully stabilized the elusive 

3

2

3

 O 

2−

  ion by complexation, paving the way for further studies on its behavior and relevance in biological and ecological processes.

In essence, the paper describes a significant accomplishment in inorganic chemistry — the stabilization of a previously elusive sulfur-oxygen species, providing insights into potential reactions in the sulfur cycle and their broader implications.

....  ion in terms of seconds or minutes. However, it's worth noting that the researchers were able to isolate and characterize the compound using X-ray structure analysis and Electron Spectroscopy for Chemical Analysis (ESCA), which implies that the compound was stable enough to undergo these analytical procedures.

Typically, X-ray crystallography requires a stable sample, meaning the compound must remain unchanged during the time it takes to collect the data, which could be hours. Furthermore, the compound was observed as a brown crystalline material, suggesting it had some level of stability.

For the precise stability duration or conditions that maintain its stability, one would need to delve deeper into the original paper or supplementary materials which might provide additional experimental details.


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