Measurement of the interaction of aqueous copper(II) with a model amyloid-β protein fragment — Interference from buffers
Bibliographic record
Abstract
For the formation of a complex of Cu2+ with the amyloid-β (Aβ) proxy N-α-dihydrourocanylhistamine (L) in unbuffered aqueous solution (pH ∼ 5.7, 25.0 °C), UV spectrophotometric measurements give a stability constant of 3.8 × 105 L mol–1. This stability constant is within the lower limit of the range of stability constants reported in the literature for complexes of Aβ with Cu2+ — as expected, in view of the smaller number of coordination sites in L. Computer modeling indicates that the Cu2+–L complex is CuL(H2O)22+, with terdentate L bound to Cu2+ via two Nπ atoms and the O atom of the peptide link. Attempts to make stability constant measurements for Cu2+ with L in aqueous solution buffered with Tris/TrisH+/ClO4– to pH near 7.2 were unsuccessful because the Tris base when in large excess over CuL2+ promoted its dissociation to Cu2+ + L by scavenging free Cu2+ as Cu(Tris)(TrisH–1)+, or when in roughly equimolar concentrations formed a ternary adduct, CuL(Tris)2+. The interactions of Cu2+ with Tris buffer were re-examined spectrophotometrically and with the aid of computations that show that the most stable Cu2+–Tris complexes are the syn- and anti-isomers of Cu(Tris)22+, but in the experimental pH ranges these are present as Cu(Tris)(TrisH–1)+. Since Cu2+(aq) is strongly complexed by almost any base capable of forming a buffer system with near-physiological pH, stability constants reported for Cu2+–Aβ complexes in any buffer solution should be regarded with skepticism unless interactions of the buffer with Cu2+ and with CuAβ2+ are taken quantitatively into account. Moreover, in vivo, biological buffers will reduce the physiological importance of Aβ–Cu2+ complexes by competing with Aβ for Cu2+.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".