9 Ligands Reveal How Tricopper(I) Clusters Bond

Nine tailored β-thioketiminate ligands show that changing one substituent’s size — not its electron-withdrawing strength — decides whether copper atoms in a tricopper(I) cluster bond to each other.

Copper(I) ions have an odd habit: pack them close enough together — inside the 2.4–3.0 Å window — and they attract each other even with no bonding electrons to share, a closed-shell d¹⁰–d¹⁰ effect chemists call cuprophilicity. It shows up in luminescent copper clusters, in catalytic copper thiolate motifs, and in the copper-thiolate binding sites of real proteins like metallothioneins and copper chaperones, where clusters of exactly this kind help cells store and shuttle copper safely. Whether a given synthetic copper(I) cluster displays this short-contact bonding, or doesn’t, has mostly been reported after the fact — a crystal structure shows Cu···Cu distances in the cuprophilic range, or it doesn’t, with little explanation of why one ligand produces it and a near-identical one doesn’t.

The Obstacle

Tricopper(I) thiolate clusters — three copper(I) ions bridged by sulfur into a six-membered ring — are one of the best-studied families for cuprophilic short contacts, and the literature already has plenty of crystal structures showing them. What it doesn’t have is a clean answer to why: existing studies discuss cuprophilic interactions between copper(I) ions in tricopper(I) thiolate clusters, but they lack clear conclusions and primarily rely on crystallographic data on the Cu···Cu short contacts as the main evidence, largely because most of those structures come from one-off ligands rather than a matched series designed to isolate a single variable at a time. Without that kind of series, there’s no way to tell whether Cu···Cu bonding is a steric effect (how much physical room the ligand leaves around the copper centers), an electronic effect (how electron-rich or electron-poor the ligand makes the copper), or some tangle of both.

The Innovation

Venkata Sai Sashankh Penki, Yu-Ting Chu, Hsing-Yin Chen, Sri Sudewi, Chien-Hung Li, Genin Gary Huang, and Sodio C.N. Hsu (Kaohsiung Medical University, National Sun Yat-sen University, and Universitas Sam Ratulangi) built exactly that matched series, published in Dalton Transactions (Penki et al., 2024, DOI: 10.1039/D4DT01549E).

The team synthesized nine β-thioketiminate (“SacNac”) ligands — a sulfur-for-oxygen swap on the well-known β-diketiminate (NacNac) ligand family — and reacted each with copper(I) tert-butoxide to form the corresponding [LCu^I]₃ tricopper clusters. Critically, the ligand set was built to separate two variables cleanly: substituents at the ortho-position of the N-aryl ring (H, NO₂, F, Cl, or bulky isopropyl/methyl groups) test steric bulk right next to the copper centers, while CF₃ groups placed on the ligand’s NCCCS chelating backbone, well away from the copper, test electronic effects in isolation. Five of the resulting clusters — [L^NO2Cu]₃, [L^F3Cu]₃, [^CF3L₂Cu]₃, [L^Cl2Cu]₃, and the bulkier [L₁Cu]₃ — were solved by X-ray crystallography, giving a direct, side-by-side structural comparison across the steric and electronic spectrum.

Key Results

Across the nine-ligand series, structural and spectroscopic evidence converge on the same conclusion: Cu···Cu bonding tracks how much room the ligand leaves around the copper centers, not how electron-rich it makes them. Bond distances shrink into the cuprophilic range when the ortho-substituent is small and open back up when it’s bulky, CO and isocyanide stretching frequencies shift most with backbone electronics rather than aryl-ring sterics, and independent DFT calculations reproduce the same ordering — three separate lines of evidence pointing the same direction.

Cu···Cu Distance Tracks Substituent Size Almost Like a Dial

[L^NO2Cu]₃ (no ortho-substituent, just H) measured 2.75±0.15 Å; [L^F3Cu]₃ (small fluorine at ortho) measured 2.78±0.13 Å — both squarely inside the 2.4–3.0 Å cuprophilic window. [L^Cl2Cu]₃ (bulkier chlorine) opened up to 3.04±0.13 Å, and [L₁Cu]₃ (bulky N-aryl isopropyl groups) landed at 3.59±0.74 Å — outside the cuprophilic range entirely, tracking van der Waals radii (H 1.20 Å, F 1.47 Å, Cl 1.75 Å, methyl-sized groups 2.0 Å) almost like a dial. A fifth cluster, [^CF3L₂Cu]₃, shows this table isn’t just about ortho-bulk: with CF₃ groups on the ligand backbone instead, it lands at an intermediate 2.95±0.05 Å — not from direct crowding, but from a “buttressing effect” where the CF₃ groups push the N-aryl rings themselves closer to copper, measurably widening the ∠N(amide)–Cu–S(inward) angle to 105° and the ∠C(amide)–N–C(aryl) angle to 122°.

Electronics and Sterics Turned Out to Be Almost Fully Decoupled

Probing the same nine LCuI fragments with CO showed that CF₃ groups on the backbone caused by far the biggest electronic shift (νCO down to 2111–2115 cm^-1, a swing of –28 to –32 cm^-1 from free CO), while F or Cl substitutions on the N-aryl ring — the same substituents driving the steric/Cu···Cu story above — caused only a minor electronic shift (νCO 2088–2091 cm^-1, essentially matching the unsubstituted L₁/L₂ clusters at 2085 cm^-1).

Isocyanide Adducts Confirm the Same Electronic Pattern

Switching to 2,4,6-trimethylphenyl isocyanide (CNR) as the probe ligand gives the identical picture: backbone CF₃ substitution again produced the largest shift (ν_CNR up to 2150 cm^-1, Δν +36 cm^-1 from free CNR), while the N-aryl ortho-substituted clusters shifted by a smaller, roughly uniform +21 to +25 cm^-1 — confirming the CO-based finding above through a second, independent probe.

Crystal Structures Confirm the Isocyanide Adduct’s Core Geometry

ORTEP structures of the CF₃L₁ (A) and CF₃L₂ (B) copper–isocyanide adducts show the same N,S-chelated Cu(I) core seen throughout this series, confirming that the ν(CNR) data above comes from a single, well-defined structural motif rather than a mix of binding geometries.

CO and Isocyanide Track Each Other Closely Enough to Swap One for the Other

Plotting Δν_CO against Δν_CNR across all nine complexes gave a clean linear fit (R² = 0.98), meaning the more experimentally awkward CO adducts (CO binds reversibly and resisted every attempt to isolate a solid) can be replaced with the far more stable, crystallizable isocyanide adducts for future electron-density studies.

One more line of evidence doesn’t show up as a figure here: DFT (Mayer bond order calculations at two levels of theory) independently reproduced the same Cu···Cu distance ordering seen by X-ray. Digitally stripping the isopropyl groups off [L₁Cu]₃ to build a hypothetical, sterically bare [L^HCu]₃ and re-optimizing its geometry predicted a Cu···Cu distance of just 2.67 Å — even shorter than the real fluorine- or hydrogen-substituted clusters — reinforcing that steric bulk, not electronics, is what’s actually setting the Cu···Cu distance.

Why ProTrusTech Is Featuring This Research

This one is a change of scenery. Every other MRID case study in this series has come out of a biosensing, photovoltaic, or thin-film lab; this paper comes out of a synthetic inorganic chemistry lab asking a fundamental bonding question that has nothing to do with detecting a molecule or harvesting light. The Methods section notes that Raman spectra were measured using a micro Raman spectroscopy system (MRID, ProTrusTech, Taiwan) equipped with a 633 nm diode laser, used here as one of several structural characterization tools — alongside X-ray crystallography, FTIR, cyclic voltammetry, and NMR — to help confirm the formation of these Cu···Cu short contacts, cross-checked against the Mayer bond order calculations.

Two things are worth calling out rather than overselling. First, this is squarely a supporting role for Raman: the paper’s central conclusions rest on X-ray crystallography and DFT, with Raman contributing corroborating evidence rather than driving the headline finding. Second, and more interesting to us: this is the same Kaohsiung Medical University group’s second consecutive Dalton Transactions paper built on MRID data, following their 2023 paper on denticity effects in related tricopper(I) and mono-copper(I) complexes (Penki et al., Dalton Trans., 2023, 52, 7652–7663) — a repeat-user relationship, not a one-off. And the 633 nm configuration used here is the same swappable second-laser option we’ve described in MRID’s architecture elsewhere on this site, this time serving a synthetic organometallic chemistry lab rather than a biosensing one.

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Why This Matters

The generalizable claim here goes beyond copper thiolates specifically: sterics and electronics don’t have to be tangled together as design variables. By placing one set of substituents at the ortho-position of a coordinating aryl ring and a chemically distinct set (CF₃) on the ligand backbone, this study shows a ligand can be tuned along two nearly independent axes — one that controls whether neighboring metal centers physically approach each other, and a separate one that controls how electron-rich the metal center is. That’s a genuinely useful design principle for anyone building luminescent Cu(I) cluster materials, copper thiolate catalysts, or synthetic models of cysteine-rich copper protein active sites, where both the metal-metal geometry and the electron density at the metal matter, often for different reasons.

Worth noting in the interest of scientific transparency: the paper itself flags, in a reviewer-response footnote, that one peer reviewer disagreed with treating the ∠Cu-S-Cu / Cu···Cu correlation as more than “a simple geometric relationship” — a reminder that even a well-supported structural trend like this one is still an active point of interpretation in the field, not a closed case.

What’s Next

• Isocyanide as the practical stand-in for CO. With Δν_CO and Δν_CNR now shown to track linearly (R² = 0.98), future electron-density studies on related LCu^I fragments have a stable, crystallizable alternative to working with reversible, hard-to-isolate CO adducts.
• Extending the steric/electronic split to other ligand backbones. The same ortho-substituent-versus-backbone-substituent logic used here could be applied to other chelating S,N- or S,S-donor ligand families to test how general this decoupling really is.
• A link back to biology. The paper’s own introduction frames tricopper(I) thiolate clusters as relevant to cysteine-rich copper(I) proteins — metallothioneins, copper chaperones, phytochelatins — suggesting this steric-tuning logic could inform synthetic models of those biological copper sites.

Working with copper, silver, or other d¹⁰ metal clusters and need Raman characterization alongside your X-ray and electrochemical data? Get in touch with our team to talk through whether our Raman systems are the right fit for your structural chemistry work.

Key Takeaways

• A matched series of nine β-thioketiminate ligands, varying N-aryl ortho-substituents and backbone CF₃ groups independently, let researchers separate steric from electronic control over tricopper(I) cluster formation.
• Cu···Cu distances ranged from 2.75 Å (cuprophilic, small ortho-substituent) to 3.59 Å (no interaction, bulky isopropyl substituent) — tracking van der Waals radii, not electron density.
• CF₃ groups on the ligand backbone, not the N-aryl ring, drove the largest electronic shifts in CO and isocyanide adduct stretching frequencies, confirming sterics and electronics as largely independent design levers.
• DFT (Mayer bond order) and a hypothetical sterically-stripped ligand model independently confirmed sterics as the dominant factor governing Cu···Cu short contacts.
• Raman spectra supporting this work were collected on ProTrusTech’s MRID system (633 nm configuration), per the paper’s Methods section — the same research group’s second consecutive Dalton Transactions paper built on MRID data.

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