Cyanide Research Articles

Catalytic Reductive Amination and Tandem Amination-Alkylation of Esters Enabled by a Cationic Iridium Complex.

Reported herein is a convenient and efficient method for one-pot, catalytic reductive amination, as well as the first multi-component tandem reductive amination - functionalization of bench-stable and readily available common carboxylic esters. This method is based on the cationic [Ir(COD)2]BArF-catalyzed chemoselective hydrosilylation of esters, followed by one-pot acid-mediated amination and nucleophilic addition. The reaction was conducted under mild conditions at a very low catalyst loading (0.1 mol% of Ir), which could be further reduced to 0.001 mol%, as demonstrated by a reaction at a 15 g scale. The method is highly versatile, allowing the use of esters with or without α-protons for the N-mono-alkylation of primary and secondary amines to produce diverse secondary and tertiary amines, as well as α-branched/functionalized amines. The method is highly chemoselective and tolerates a variety of functional groups such as bromo, trifluoromethyl, ester, and cyano groups. The value of the method was demonstrated by the one-step catalytic synthesis of two bio-relevant N-mono-methyl α-amino esters and the antiparkinsonian agent piribedil, as well as by the use oftwo shorter chain triglycerides as alkylating feedstock.

Structure-activity relationships between nitrile analogues and acaricidal activities against Haemaphysalis longicornis.

A recent increase in severe fever with thrombocytopaenia syndrome (SFTS) virus cases in Korea has been observed. This virus attacks humans and animals, and no drug is available for its treatment. This study is investigating potential control measures targeting the causative agent, Haemaphysalis longicornis. Lepidium meyenii oil was ≈8.3-, 4.2- and 4.1-fold more active than diethyltoluamide against H. longicornis larvae, nymphs and adults, respectively. The major components of L. meyenii oil were identified as benzyl nitrile (71.64%), followed by ethyl linoleic acid (13.32%), ethyl palmitate (7.81%) and 3-methoxybenzyl nitrile (2.10%). In testing individual components of the oil were tested against H. longicornis adults, the half-maximal lethal dose (LD50) values for benzaldehyde, benzyl nitrile and benzyl isothiocyanate were found to be 9.21, 9.19 and 18.26 μg cm-3, respectively. The acaricidal component was isolated and identified as benzyl nitrile. To establish the structure-activity relationships between nitrile analogues and acaricidal activities, benzyl nitrile (LD50: 0.56, 6.38 and 9.19 μg cm-3) exhibited the highest acaricidal activities against H. longicornis larvae, nymphs and adults, followed by benzoyl nitrile (3.24, 8.36 and 15.47 μg cm-3), phenyl nitrile (5.45, 9.35 and 17.48 μg cm-3) and diethyltoluamide (7.95, 14.81 and 22.12 μg cm-3). However, the presence of allyl, methyl or vinyl functional groups bound to the nitrile group abolished the acaricidal activity. These results demonstrate that L. meyenii oil, benzyl nitrile, benzoyl nitrile and phenyl nitrile represent suitable options for the secure management of H. longicornis. Nevertheless, additional research is essential to develop formulations that enhance the efficacy and safety of the aforementioned acaricides. © 2024 Society of Chemical Industry.

Conjugated phthalocyanine-based framework as artificial SEI for over 400 Wh kg−1 lithium metal battery

Abstract High-voltage lithium metal batteries (HVLMB) are appealing candidates for next-generation high-energy rechargeable batteries, but practical applications are still limited by the severe capacity degradation, attributed to the poor interfacial stability and compatibility between the electrode and electrolyte. In this work, a two-dimensional conjugated phthalocyanine framework containing single cobalt atoms (CoSAs-CPF) is developed as a novel artificial solid electrolyte interphase (SEI), where a large amount of charge is transferred to the CPF skeleton due to the Lewis acid activity of the Co metal sites and the strong electron-absorbing property of the cyano group (−CN), greatly enhancing the adsorption of Li+ and regulating Li+ distribution toward dendrite-free Li-metal batteries, superior to most of the reported SEI membrane. As a result, the Li||Li symmetrical cell with CoSAs-CPF modified Li-anodes (CoSAs-CPF@Li) exhibits a low polarization with an area capacity of 1.0 mAh cm−2 over 3500 h. The LiFePO4||CoSAs-CPF@Li (LFP: 20 mg cm−2) delivers an ultra-long cycling life up to 1000 cycles with a high-capacity retention of 98.6%. Remarkably, the high-voltage LiNi0.8Co0.1Mn0.1O2||Li@CoSAs-CPF (NCM811: 10 mg cm−2) demonstrates a long cycling life over 800 cycles with a high-capacity retention of 80%. Meanwhile, in-situ ultrasonic transmission technology confirms the admirable ability of artificial CoSAs-CPF SEI to stabilize the Li-anode interface in pouch cells during cycling. Remarkably, the NCM811||Li@CoSAs-CPF pouch cell exhibits an energy density of 421 Wh kg−1 and keeps 130 cycles with a low electrolyte/capacity ratio of 2.5 g Ah−1. The strategy of constructing CoSAs-CPF-reinforced Li-anode provides a promising direction for high-energy-density HVLMB with long-cycling stability.

Recasting the wobbling-in-a-cone model for the rotational anisotropy of phenylselenocyanate in poly(methyl methacrylate): Effect of internal bond rotation and polymer segmental motion.

The rotational anisotropy of a molecule in a constrained environment is modeled by wobbling-in-a-cone (WIAC) motion, which describes the angular space sampled by the molecule. Recent polarization-selective IR pump-probe measurements have applied this model to phenylselenocyanate in amorphous polymers, aiming to probe the surrounding free volume. A faster rotational timescale was hypothesized to reflect the angular space within the static voids of the polymer matrix, while a slower timescale relates to constraint release by the polymer backbones. To better quantify the contributions of internal bond rotation and polymer segmental motion, we conduct molecular dynamics simulations on two phenylselenocyanate variants with different internal rotational barriers, as well as on p-chlorobenzonitrile, which lacks such internal rotational freedom, within a polymer matrix. Our analyses reveal that the faster (∼10ps) component of the cyano group's anisotropy decay arises from concurrent angular sampling due to internal bond rotation and WIAC motion. Conversely, polymer segmental motion was found to have a minimal influence on the slow (∼200ps) anisotropy component. Based on these findings, we refine the WIAC model to better link rotational diffusion with the distinct free volume elements accessed by the probe molecule. This revised model allows the quantification of free volume elements associated with both internal bond rotation and wobbling motion within the polymer cage.

Three‐Component Alkylsulfonylation of 1‐Acryloyl‐2‐cyanoindoles with Hantzsch Esters through Sulfur Dioxide Insertion

A three‐component alkylsulfonylation/cyclization/ hydrolysis relay reaction of 1‐acryloyl‐2‐cyanoindoles with 4‐alkyl Hantzsch esters and Na2S2O5 to access a series of alkylsulfonyl pyrrolo[1,2‐a]indolediones derivatives involving in situ sulfur dioxide insertion is established. With this method, a variety of primary and secondary alkyl radicals can be used for trapping sulfur dioxide and in situ formed corresponding alkylsulfonyl radical intermediates, followed by alkyl sulfonyl radical addition, cyclization and hydrolysis. In addition, this reaction goes through once selective cleavage of σ carbon‐carbon bond and following successively formation of three new chemical bonds, in which cyano group acts as the dual roles, including the radical acceptor and carbonyl source.

Guidance on surface cyclization reactions through coordination structures.

Metal coordination structures, formed through interactions between metal atoms and active functional groups, are crucial in determining the reaction pathway and its products. This study examines 2,3-dibromo-6,7-dicyanonaphthalene (DDN), which contains cyano and halogen groups, deposited on Au(111) and Ag(111) surfaces, using scanning tunneling microscopy at room temperature. The reason for the formation of various cyclization products on the Au(111) surface is that the bromine of DDN and the cyano group have overlapping reaction temperature ranges. This overlap leads to the coexistence of C-C coupling products from the debromination sites and cyclization products from the cyano groups. In contrast, on the Ag(111) surface, the final cyclization reaction produces a single type of polymer directly induced by the metal-coordinated structures. The synergistic effects between coordination structures and the activation temperatures of molecular reaction groups are crucial factors in regulating polymerization reactions.

Dual Photoredox/Copper-Catalyzed Three-Component Alkylcyanation of Alkenes and 1,4-Alkylcyanation of 1,3-Enynes Employing Sulfoxonium Ylides as the Carbon Radical Precursors.

A novel dual photoredox/copper-catalyzed three-component alkylcyanation of alkenes and 1,4-alkylcyanation of 1,3-enynes have been developed. In this radical cyanoalkylation reaction, the photoredox induced alkyl radical from sulfoxonium ylides adds to the carbon-carbon double bonds of styrenes or 1,3-enynes, and the generated benzylic or allenyl radicals couple with a Cu(II) cyanide complex to achieve selective cyanation. The reaction exhibits high chemo- and regioselectivity and a wide substrate scope, providing an efficient method for the synthesis of alkyl nitriles and allenyl nitriles in a single step.

Inverse Electron Demand Diels-Alder Reaction of Pyrazines with 2,5-Norbornadiene as Acetylene Precursor

Herein, we report the reaction of pyrazines with 2,5-norbornadiene, an acetylene precursor, as a cascade of Diels-Alder reactions yielding substituted pyridines. In contrast to the known examples of intermolecular Diels-Alder type reaction of pyrazines with acetylene, which usually leads to a mixture of products, in our case the formation of a single isomer was observed. The proposed approach allows the conversion of pyrazines with different types of substitution, except those containing methyl and amino donor groups, to pyridines. In addition, highly functionalized aminonicotic esters were obtained, which can be used for the synthesis of bioactive compounds. An unusual course of the Diels-Alder reaction was found in the case of tetrasubstituted pyrazines, which cleave organic nitriles instead of HCN. Quantum-chemical modeling of possible transition states showed that this Diels-Alder reaction proceeds via cycloaddition of 2,5-norbornadiene to pyrazine with sequential elimination of HCN and cyclopentadene; the reaction pathway including initial formation of acetylene from norbornadiene and subsequent Diels-Alder reaction with the acetylene was rejected as kinetically unfavorable.

Pseudohalogen regulation of benzimidazole small molecule acceptor to optimize molecular crystallinity in Q-PHJ organic solar cells

The cyano group is a pseudohalogen with chemical properties similar to halogens. It has the ability to regulate the stacking and energy levels of molecules in organic solar small molecule non-fullerene acceptor materials. In this study, we introduce two novel alkylated derivatives, BMIC-CN-Me and BMIC-CN-iPr, featuring a cyano-modified benzimidazole core. This central nucleus design is reported for the first time, offering a unique approach to molecular engineering in organic photovoltaics. BMIC-CN-Me, in particular, enhances device performance by meticulously managing molecular stacking through steric hindrance. Analysis via single-crystal X-ray diffraction reveals five distinct stacking modes, with an average intermolecular distance of approximately 3.31 Å, optimizing the efficiency of charge transfer. This precise molecular arrangement elevates the photoconversion efficiency (PCE) of the non-fullerene acceptor, based on the benzimidazole core, to an impressive 17.6 %. Moreover, the material demonstrates exceptional stability, retaining over 80 % of its initial efficiency after 1200 h in a glove box and maintaining more than 80 % of its original efficiency after 500 h of continuous simulated solar irradiation. Compared to the 2-methylimidazole-derived molecules acceptor, devices prepared using BMIC-CN-Me demonstrate superior performance due to their better-matched energy levels and UV–Vis absorption spectrum. Furthermore, when contrasted with BMIC-CN-iPr, BMIC-CN-Me exhibits a more tightly packed molecular arrangement. These factors contribute to more effective exciton dissociation, accelerated charge transport, and the suppression of recombination, leading to an enhanced fill factor and overall photoelectric conversion efficiency. The quasi-planar heterojunction architecture further bolsters device stability. The cyano-modified benzimidazole structure provides additional non-covalent interaction sites, which augment the material’s stability. Our findings indicate that the cyano substitution of the benzimidazole core not only enhances material stability and molecular aggregation but also significantly improves the performance of organic solar cells. This innovative approach to molecular design holds promise for the development of high-performing and durable organic photovoltaic materials.

Comprehensive insight into the interfacial adsorption mechanism of pyridine derivatives by molecular dynamics simulations, GFN-xTB and first-principles calculations

The application of computational chemistry methods is becoming increasingly prosperous in the interfacial adsorption study of corrosion inhibitors. In this work, three typical computational chemistry methods, molecular dynamics (MD) simulations, GFN-xTB and first-principles calculations, were employed to investigate the interfacial adsorption processes of four pyridine derivatives (CP, ACP, DPA and ABOP) on Fe surface. With related to the measured corrosion inhibition efficiencies of the four pyridine derivatives for mild steel in HCl solution by weight loss and electrochemical tests, the calculated results by these three methods were compared in terms of the adsorption configurations, bonding mode, and the adsorption strength (adsorption energy). Based on the radical distribution function (RDF) from MD simulations, it is only roughly inferred that pyridine derivatives can chemically adsorb on Fe surface. While both GFN-xTB and first-principles calculations indicate that the adsorptions of the four pyridine derivatives are through the N and unsaturated C atoms. In particular, compared to DPA and ABOP molecules, the cyano groups (−CN) of CP and ACP molecules exhibit outstanding adsorption capacity, which endow CP and ACP with better inhibition performances.

Wave-transparent and eco-friendly flame-retardant phosphorus-based phthalonitrile/quartz composites by a synchronized self-curing strategy with cyano and alkynyl groups

The robust human–machine interaction systems of the aerospace industry necessitate the development of thermal resistant wave-transparent composites, with a pivotal focus on organic resin matrix. However, enhancing the heat resistance of such materials while preserving other critical attributes has been a formidable challenge. In this study, a novel designed strategy of a dual-curing functional phosphorus-based phthalonitrile monomer (P-ALK-PN) has been proposed. The optimized curing temperatures for intra- or intermolecular Diels-Alder reactions of alkynyl groups and polyaddition reaction of cyano groups resulted in a homogeneous and highly crosslinked N-enriched phthalonitrile system. After curing at 450 °C, the resin, namely P-ALK-PN-450 °C, demonstrated exceptional thermal stability (T5% = 644 °C), thermo-oxidative stability (T5% = 554 °C), and char yield at 800 °C (90.7 % in N2 and 67.5 % in air). Their quartz fiber reinforced composites (P-ALK-PN/QFs) were subsequently fabricated by the hot-pressing process. Upon post-curing at 420 °C, P-ALK-PN-420 °C/QF displayed elevated glass transition temperature (550 °C), flexural strength (319 MPa), and relatively low dielectric properties with a dielectric constant (Dk) of approximately 4.2 and a dissipation factor (Df) less than 0.02 across a wide temperature ranging from 25 °C to 600 °C. Especially, it exhibited excellent flame retardancy (only a 6.7 % weight loss at ambient temperatures exceeding 1300 °C for 200 s) as well, stemming from release of eco-friendly inert gases (NH3) and formation of a graphitized protective layer during pyrolysis. These promising results highlight the potential applications of P-ALK-PN resins in aerospace and high-performance engineering fields.

Improved property of block copolymer-based anion exchange membranes by attaching multi-ion flexible strings

To meet high conductivity and sufficient anti-swelling of anion exchange membranes (AEMs), a collaborative strategy of combining multi-ion flexible string and block backbone is adopted to construct membrane’s architecture. Then a series of adamantane-contained poly(arylether ketone nitrile)s block copolymers has been synthesized and grafted with multi-ion flexible strings to form hydrophilic domains. In addition, the hydrophobic segments with nitrile groups are aimed to enhance the entanglement between chains and limit swelling degrees of membranes. Along the steps, clear phase separation morphologies are formed for creating efficient ionic channels. The resulted AEMs exhibit improved conductivity and dimensional stability at low hydration levels, e.g. conductivity of 91.7−119.4 mS cm-1, swelling ratio (SR) of 14.4%−19.5%, water uptake (WU) of 38.3%−57.9% and λ values of 13.4−15.7 at 80 °C. Furthermore, the AEMs prepared exhibit excellent mechanical properties and good thermal stability below 180 °C. However, further optimization is required for a better alkaline stability.

Facile access to spirobifluorene-fused chiral multi-resonance materials with ultra-narrowband blue emission

Narrowband multiple resonance (MR) emitters with circularly polarized luminescence (CPL) hold significant promise for three dimension organic light-emitting diode (3D-OLED) displays. In this work, we present a simple method for developing a new type of 9,9’-spirobifluorene-based CP-MR emitters by a recrystallization resolution technology and chlorine (Cl)-directed electrophilic borylation reaction, both of which significantly enhances the efficiency and scalability for mass production. This approach allows for integrating an asymmetric 9,9’-spirobifluorene core between two MR frameworks to achieve optically active CP-MR emitters. The highly rigid spirobifluorene framework minimizes structural relaxation, and meanwhile, the introduction of a cyano (CN) group enhances the MR emission characteristics, leading to an ultra-narrowband blue emission with full width at half maximum (FWHM) of 14 nm. As a result, these molecules facilitate the assembly of narrowband blue CPL-OLEDs with a maximum external quantum efficiency (EQEmax) of 30.7% and an impressive narrow FWHM of 16 nm, representing the first instance of an FWHM below 20 nm in CPL-OLEDs.

Cyano-modified Potassium-Sodium Poly(Heptazine Imide) Nanosheets for Photocatalytic Hydrogen Peroxide Reduction Coupled with 5-hydroxymethylfurfural Oxidation

The efficacy of poly(heptazinonimide) (PHI) materials in photocatalytic applications is often constrained by limited visible light absorption and charge separation. In this study, we successfully synthesized cyano-modified potassium-sodium poly(heptazinonimide) (KNPHI) nanosheets using a molten salt method, which significantly enhances photocatalytic performance. The resulting KNPHI nanosheets achieve hydrogen peroxide (H₂O₂) concentrations up to 8.64mM, nearly 1.9 and 123 times greater than that achieved by KPHI and PCN respectively. Notably, integrating cyano groups and potassium-sodium ions within KNPHI enhances visible light absorption, intermediate adsorption and charge separation, as confirmed by experimental characterizations and DFT calculations, thereby improving the oxygen reduction reaction efficiency. Furthermore, the use of KNPHI for 5-hydroxymethylfurfural oxidation, coupled with oxygen reduction reaction pathway, was systematically investigated. These findings offer promising avenues for the development of advanced photocatalysts that support sustainable energy production and green chemical synthesis.

A new indanone based dyes bearing dicyanomethylene and salicylidene moieties for selective detection cyanide anion and aromatic amines

Novel chemosensors that are indan-1-one dyes bearing salicylidene moiety were synthesized with good yields and characterized by FT-IR, 1H NMR, 13C NMR, and HRMS methods. Moreover, the molecular structure of 7 was characterization by X-ray and Environmental scanning electron microscopy (ESEM) analyses. The chemosensor potential of dyes were examined in a variety of basic conditions that include various anions, organic amines, and pH ranges by absorption and fluorescence spectra. The naked-eye detection of instant color changes was also observed. The deprotonation mechanism between dyes and anions was investigated by reversibility and 1H NMR studies. pKa values were determined in buffer solution with pH 6–11. Furthermore, organic amines were investigated and found they have two different interaction mechanism, deprotonation and addition. Density Functional Theory (DFT) were used for supporting the experimental results. In addition, the second-order nonlinear optical property of dyes were investigated and showed moderate μβ values.

SYNTHESIS AND PHOTOPHYSICAL PROPERTIES OF NEW DIPHENYLACRYLONITRILE-BEARING ALDEHYDES

Background: The cyano group is well-known for its strong electron-withdrawing properties, Effective in producing acrylonitrile when added to ?-conjugated alkene structures. The twisted structures of acrylonitrile help avoid the ACQ phenomenon and induce AIE properties, making acrylonitrile units important in various applications. Aims: Synthesis of acrylonitrile units via cyano aldol condensation by temperature control and study of AIE activity. Methods: The synthesis of diphenyl acrylonitrile units took place in two steps: 1- By o-arylation, linear aldehydes were synthesized, 2- Gradually adding p-ansiyl cyanide to the linear aldehydes in a round flask containing methanol and KOH. Results: Diphenyl acrylonitrile units were synthesized, and their structures were identified using IR, 1HNMR, 13CNMR, and mass techniques. The photophysical results indicated that diphenylacrylonitrile-bearing aldehyde compounds have fluorescence with a wavelength ranging between 400-500 nm and moderate AIE activity. Discussion: The prepared diphenylacrylonitrile-bearing aldehydes units showed moderate AIE activity in the aggregation state, where the fluorescence intensity increases with increasing water percentage in the THF/H2O mixture and reaches its peak at 80%. The reason lies in the fact that the cyano group forms acrylonitrile with twisted structures, which avoids ACQ and enhances the AIE properties. Conclusions: by controlling the temperature and through a facile aldol condensation, phenylacrylonitrile units were synthesized in good yields. Their photophysical properties were studied, and they were found to have moderate AIE activity.

Nitrogen-defective protonated porous C3N4 nanosheets for enhanced photocatalytic hydrogen production under visible light

Defect engineering with morphology control is strategy to tailoring photocatalytic performance of carbon nitride (C3N4) for producing clean hydrogen (H2). Herein, a kind of protonated C3N4 porous nanosheets with nitrogen-defects of N1-vacancy and cyano group (named C3N4-ND) was simple synthesized. In the process, the strong oxidizing nitric acid was used skillfully to introduce N1-vacancy and -CN group into C3N4 and achieves protonation. The nitrogen-defects engineering can shorten band gap, improve the separation of photogenerated carriers. And the defect site, can used as active center and effectively adsorb H+ for efficient photocatalytic hydrogen evolution performance. Simultaneously, the porous nanosheets greatly increase specific area enhanced contact with light and reaction fluids and more reactive sites than bulk C3N4 (BCN). Thus, the C3N4-ND can obtain brilliant photocatalytic hydrogen evolution performance. Typically, C3N4-ND1.7 exhibits excellent photocatalytic H2 evolution rate up to 1.12 mmol·g−1·h−1 for photocatalytic water splitting (PWS) and 39.18 mmol·g−1·h−1 for photocatalytic hydrogen evolution (PHE, 0.5 vol% TEOA as sacrificial agent) under visible light, which has 22.4 and 75.34 times increase over BCN, respectively. This work confirmed the positive effect of defect and morphology engineering on improving the photocatalytic hydrogen evolution performance of C3N4.

Nickel-catalyzed cyanation of C—S bond using CO2 and NH3

Catalytic cleavage of C—S bonds is an important approach in the construction of functionalized molecules. Herein, we developed the catalytic synthesis of nitriles from thioethers, utilizing CO2 as the carbon source for the first time. This work addressed the challenge of avoiding toxic cyanides by generating the “CN” group via isocyanate intermediates from CO2 and NH3 with the aid of Ni-phosphine catalysts and hydrosilane. A wide range of aryl thioethers were efficiently converted into the corresponding aryl nitriles, demonstrating good functional groups tolerance including fluorine, morpholine, piperazine amide, and cyano group. Additionally, chloride anion played essential roles probably through facilitating the generation of Ni (I) species by promoting Ni—S bond cleavage, thus enhancing the overall reaction efficiency.

Molecular structures of residual solvent in polyacrylonitrile based electrolytes: Implications for conductivity and stability.

Lithium-ion batteries increasingly play significant roles in modern technologies; however, increased energy density also raises concerns about electrolyte safety. Traditional electrolytes that use volatile organic solvents face risks of thermal runaways and fires from electrode shorting. In response, polymer-based solid electrolytes have been developed for replacement. Polyacrylonitrile (PAN) is a promising fire-resistant component for electrolyte fabrication, but its limited solubility necessitates using low-volatility solvents, which are notoriously difficult to remove in subsequent drying processes. Here, we use femtosecond two-dimensional infrared spectroscopy to provide an in-depth understanding of how residual solvent from processing affects the molecular structures and dynamics within a polymer electrolyte. To this end, linear and nonlinear infrared spectroscopies are employed to interrogate the molecular interactions in PAN-based electrolytes containing various contents of N,N-dimethylformamide (DMF). We show that the amount of DMF within the PAN electrolyte affects the Li+ structure. The coordination can proceed through the carbonyl group and/or the amide nitrogen to form antiparallel structures with the nitrile groups of PAN through dipole-dipole interactions. The free motion of DMF is drastically inhibited upon interaction with Li+ and PAN, which decreases the ionic conductivity and potentially affects the stability (resistance toward removal and chemical decomposition). These findings have implications for the design and processing of solid polymer electrolytes.

Photochemical and Collision-Induced Cross-Linking of Asp, Glu, Asn, and Gln Residues in Peptide-Nitrile Imine Conjugate Ions in the Gas Phase.

Peptide conjugates furnished with a 2,5-diaryltetrazolecarbonyl tag at the C-terminal lysine, which we call peptide-tet-K, were found to undergo efficient cross-linking of Asp, Glu, Asn, and Gln residues to transient nitrile-imine intermediates produced by photodissociation and collision-induced dissociation (CID) of the tetrazole ring in gas-phase ions. UV photodissociation (UVPD) at 213 nm achieved cross-linking conversion yields of 37 and 61% for DAAAK-tet-K and EAAAK-tet-K, respectively. The yields for NAAAK-tet-K and QAAAK-tet-K were 29 and 57%, respectively. Even higher cross-link yields were found for CID-MS3 of stable denitrogenated ions, (peptide-tet-K-N2 + H)+, that were in the 69-83% range. Different types of cross-links were distinguished by CID-MSn that showed a distinct series of backbone fragment ions, loss of N-terminal groups, and loss of phenylhydrazine from the modified nitrile imines. The Asp and Glu side-chain carboxyl groups were major participants in cross-linking that resulted in proton and oxygen transfer to the nitrile imine group. Other types of cross-linking involved Asn and Gln CONH2 groups and backbone amides. Cyclic ion mobility-mass spectrometry was used to separate NAAAK-tet-K and QAAAK-tet-K conformers and products of their collision-induced denitrogenation. Linear nitrile-imine and cross-linked ion structures were identified by comparing the experimental collision cross sections (CCSexp) to those for structures obtained by combined Born-Oppenheimer molecular dynamics and density functional theory (DFT) calculations. The formation of cross-links was found to be energetically favorable and involved proton-facilitated nucleophilic attack at the nitrile-imine carbon atom.