Direct Bond Research Articles

Comparison of Bracket Placement Accuracy Between Direct and Indirect Bonding: A Literature Review

Comparison of Bracket Placement Accuracy Between Direct and Indirect Bonding: A Literature Review

Covalent vs. Dative Bonding in Carbon Monoxide and Other 10-Valence-Electron Diatomics.

Valence bond theory (VB) was used to determine the extent and driving forces for covalent vs. dative bonding in 10-valence-electron diatomic molecules N2, CO, NO+, CN-, P2, SiS, PS+, and SiP-. VBSCF calculations were performed at the CCSD(T)/cc-pVDZ optimized geometries. The full triply bonded system included 20 VB structures. A separation of the σ and π space allowed for a subdivision of the full 20 structure set into sets of 8 and 3 for the π and σ systems, respectively. The smaller structure sets allowed for a more focused look at each type of bond. In situ bond energies for σ bonds, individual π bonds, the π system, and triple bonds follow expected trends. Our data shows that N2 and P2 have three covalent bonds whereas CO and SiS contain two covalent and one dative bond, and charged species NO+, CN-, PS+, and SiP- are a mixture of N2 and CO type electronic arrangements, resulting in a nearly equal charge distribution. Dative bonds prefer to be in the π position due to enhanced σ covalency and π resonance. Both σ and π resonance energies depend on a balance of ionic strength, orbital compactness, σ constraints, and bond directionality. Resonance energy is a major contributor to bond strength, making up more than 50% of the π bonds in SiS and PS+ (charge-shift bonds), and is greater than charge transfer in dative bonds.

Asymmetric Proton-Exchange-Enhanced Lithium Niobate and Silicon Low-Temperature Direct Bonding with an Ultrathin Heterogeneous Interface.

The integration of lithium niobate (LiNbO3 or LN) and silicon (Si) has emerged as a promising heterogeneous platform for microelectromechanical systems (MEMSs) and photonic integrated circuits (PICs). Particularly, the lithium niobate on silicon (LNOS) architecture leverages the superior piezo-optomechanical properties of LN, making it compatible with superconducting circuits and quantum systems. This opens an avenue for the development of advanced quantum sensors and processors. However, existing LN and Si bonding methods suffer from inherent limitations, such as low interfacial strength and the formation of thick, amorphous interlayers. In this work, we present an asymmetric surface activation strategy to address these challenges. By employing proton-exchange-enhanced chemical activation on the LN surface and oxygen plasma treatment on the Si side, we have achieved remarkable bonding strengths of up to 10 MPa at a moderate annealing temperature of 150 °C. Notably, the bonding mechanism in our approach differs from that in conventional diffusion-based processes. Here, the dehydration condensation of surface functional groups results in an exceptionally thin interfacial layer, less than 2 nm thick, without the presence of amorphous LN. This innovative fabrication method for LNOS demonstrates superior reliability, piezoelectric performance, thermal management capabilities, and optical transmission qualities, paving the way for cutting-edge photonic and quantum applications.

Synthesis of Bimetallic Dinuclear Hydrido Complexes of Re and Rh/Ir Supported by a Direct M-M' Bond: The Role of the M-M' Bond in the Site Exchange of Hydrides.

Heterometallic tetrahydrido complexes [Cp*Re(H)2(μ-H)2MCp*] (5a: M = Ir, 5b: M = Rh) were synthesized by the reaction of [Cp*ReH6] and [Cp*M(sol)3]2+ (M = Ir, Rh) followed by deprotonation. Although 5 possesses four hydrides and adopts a 30-electron configuration as [Cp*Ru(μ-H)4RuCp*] (1) does, the positions of the hydrides in 5 differ from those in 1: two terminal and two bridging hydrides. In addition, adaptive natural density partitioning (AdNDP) analysis demonstrated that a direct Re-M bond is held in 5. Although cationic pentahydrido complexes [Cp*Re(H)2(μ-H)3MCp*]+ (4a: M = Ir, 4b: M = Rh) do not contain a direct Re-M bond, the formation of a Re-M bond in the intermediate of the hydride site exchange was also inferred by DFT calculations. DFT calculations suggested that the Re-M bond plays a crucial role in the site exchange of hydrides in 5 and 4. While μ-phosphido complex [Cp*(PPh3)Re(H)(μ-H)(μ-PPh2)Ir(H)Cp*] (6) was obtained by the reaction of 5a with PPh3, the treatment of 5a with PMe3 resulted in the formation of a 1:1 mixture of [Cp*Re(H)2(PMe3)2] and [Cp*Ir(H)2PMe3] via the rupture of the Re-Ir bond.

Glycerol Vapor Assisted Cu Direct Bonding: Implications for 3D Semiconductor Packaging

AbstractAs the scaling down of semiconductor devices reaches its physical limits, 3D stacking packaging technology is emerging as a new miniaturization solution. Among the various 3D packaging technologies, Cu direct bonding is widely adopted due to copper's excellent electrical conductivity and the absence of intermetallic compounds for solder bumps. Since copper readily undergoes oxidation, technologies that prevent Cu surface oxidation during Cu direct bonding are essential. However, current research suggests that the methods require additional pretreatment processes, which demand high costs. In this study, a Cu direct bonding method utilizing glycerol vapor is developed to effectively streamline the pretreatment steps. The potential of glycerol as a reducing agent and antioxidant for Cu is demonstrated using a silicon die sample with a size of 10 × 10 mm2, verified through the X‐ray photoelectron spectroscopy. The Cu direct bonding for 3D semiconductor packaging is successfully performed under glycerol vapor atmosphere, without any plasma pretreatment. The cross‐section of the bonded specimens is examined by scanning electron microscopy, and mechanical reliability is assessed by die shear testing.

Diverse Self-Assembled Molecular Architectures Promoted by C-H···O and C-H···Cl Hydrogen Bonds in a Triad of α-Diketone, α-Ketoimine, and an Imidorhenium Complex: A Unified Analysis Based on XRD, NEDA, SAPT, QTAIM, and IBSI Studies.

X-ray structural elucidation, supramolecular self-assembly, and energetics of existential noncovalent interactions for a triad comprising α-diketone, α-ketoimine, and an imidorhenium complex are highlighted in this report. Molecular packing reveals a self-assembled 2D network stabilized by the C-H···O H-bonds for the α-diketone (benzil), and the first structural report of Brown and Sadanaga stressing on the prevalence of only the van der Waals forces seems to be an oversimplified conjecture. In the α-ketoimine, the imine nitrogen atom undergoes intramolecular N···H interaction to render itself inert toward intermolecular C-H···N interaction and exhibits two types of C-H···O H-bonds in consequence to generate a self-assembled 2D molecular architecture. The imidorhenium complex features a self-aggregated 3D packing engendered by the interplay of C-H···Cl H-bonds along with the ancillary C-H···π, C···C, and C···Cl contacts. To the best of our knowledge, in rhenium chemistry, this imidorhenium complex unravels the first example of self-associated 3D molecular packing constructed by the directional hydrogen bonds of C-H···Cl type. The presence of characteristic supramolecular synthons, viz., R2 2(12), R2 2(16), and R2 2(14), in the α-diketone, α-ketoimine, and imidorhenium complex, respectively, has prompted us to delve into the energetics of noncovalent interactions. Symmetry-adapted perturbation theory analysis has authenticated a stability order: R2 2(14) > R2 2(12) > R2 2(16) based on the interaction energy values of -25.97, -9.93, and -4.98 kcal/mol, respectively. The respective average contributions of the long-range dispersion, electrostatic, and induction forces are 58.5, 32.8, and 8.7%, respectively, for the intermolecular C-H···O interactions. The C-H···Cl interactions experience comparable contribution from the dispersion force (57.9% on average), although the electrostatic and induction forces contribute much less, 28.0 and 14.1%, respectively, on average. The natural energy decomposition analysis has further attested that the short-range, interfragment charge transfer occurring via the lp(O/Cl) → σ*(C-H) routes contributes 17-25% of the total attractive force for the C-H···O and C-H···Cl interactions. Quantum theory of atoms in molecules analysis unfolds a first-order exponential decay relation (y = 8.1043e -x/0.4095) between the electron density at the bond critical point and the distance of noncovalent interactions. The distances of noncovalent interactions in the lattices are internally governed by the individual packing patterns rather than the chemical nature of the H-bond donors and acceptors. Intrinsic bond strength index analysis shows promise to correlate the electron density at BCP with the SAPT-derived interaction energy for the noncovalent interactions. Two factors: (i) nearly half the HOMO-LUMO energy difference for the imidorhenium complex (∼30 kcal/mol) compared to the organics, and (ii) ∼60% localization of HOMO over the mer-ReCl3 moiety clearly indicate an enhanced polarizability of the complex facilitating the growth of weak C-H···Cl H-bonds.

Impact of phosphonate and phosphoramidate in Si/P/triazine hybrid flame retardants on cotton flammability

Phosphorus and nitrogen-containing flame retardants are well-known for their high efficacy when used in combination, either as separate compounds or within the same molecule. However, a detailed examination of the chemical bonding of phosphorus is needed to understand the flame behavior. To this end, two different scenarios were examined and compared with a phosphorus-free benchmark. Both scenarios contain a triazine ring and a silane-based precursor. The first scenario involves a direct bond between phosphorus and triazine (phosphonate), while the second involves a bridging of phosphorus and triazine via nitrogen (phosphoramidate). This allowed to investigate the structural effect of phosphoramidate and phosphonate of triazine derivatives on the thermal and flame retardant behavior. The flame-retardant performance and mechanism of the treated samples were investigated by means of the vertical flame test (DIN EN ISO 15025), thermogravimetric analysis and microscale combustion calorimetry, amongst others. Our research shows that triazine-based phosphonate has a better flame retarding effect on cotton than phosphoramidate at the same phosphorus concentration. Self-extinguishing characteristics was observed at a low add-on value of 0.23 mmol/g for phosphonate-based flame retardant, while a higher add-one value of 0.24 mmol/g was required in the case of phosphoramidate. The comprehensive analysis demonstrated that both flame retardants undergo mechanisms in both the gas phase and condensed phase by releasing incombustible gases and promoting the carbonization of cotton fabrics.

Full Picture of Energy Transfer in a Trivalent Europium Complex with Bidentate β-Diketonate Ligand.

Trivalent europium (Eu(III)) complexes emit narrow-band luminescence as a result of energy transfer following the photoexcitation of antenna ligands. Bidentate β-diketonates are typically used as antenna ligands; however, their entire energy transfer mechanism to Eu(III) remains unknown. We used time-resolved photoluminescence spectroscopy and femtosecond transient absorption spectroscopy to map the complete intramolecular energy transfer process in the [Eu(hfa)3(TPPO)2] (hfa = hexafluoroacetylacetonate, TPPO = triphenylphosphine oxide) complex; hfa is a β-diketonate antenna ligand. Our analysis provides a "full picture" of energy transfer, tracing each step from initial photoexcitation to final relaxation: intersystem crossing in the ligands, energy transfer from the ligands to the metal center, and multiple internal conversion of Eu(III). We demonstrated that the direct bonds of the bidentate ligands enabled a quick and near-unity-efficiency energy transfer from the triplet state of the ligand to the 5D2 state of Eu(III). We also revealed that the loss of the ligand-centered intersystem crossing process reduces the overall sensitization efficiency. Our findings provide a foundation for the rational design of advanced luminescent materials, paving the way for advances in lanthanide-based luminescence research.

Dual-tuned floating solenoid balun for multi-nuclear MRI and MRS

Common-mode currents can degrade the RF coil performance and introduce potential safety hazards in MRI. Baluns are the standard method to suppress these undesired common-mode currents. Specifically, floating baluns are preferred in many applications because they are removable, allow post-installation adjustment and avoid direct soldering on the cable. However, floating baluns are typically bulky to achieve excellent common-mode suppression, taking up valuable space in the MRI bore. This is particularly severe for multi-nuclear MRI/MRS applications, as two RF systems exist. In this work, we present a novel dual-tuned floating balun that is fully removable, does not require any physical connection to the coaxial cable, and has a significantly reduced footprint. The floating design employs an inductive coupling between the cable solenoid and a floating solenoid resonator rather than a direct physical connection. Unlike the previous floating solenoid balun, this balun employs a two-layer design further to improve the mutual coupling between the two solenoids. A pole-insertion method is used to suppress common-mode currents at two user-selectable frequencies simultaneously. Bench testing of the fabricated device at 7 T demonstrated high common-mode rejection ratios at Larmor frequencies of both 1H and 23Na, even with a compact dimension (diameter 18 mm and length 12 mm). This balun's removable, compact, and multi-resonant nature enables light-weighting, allows more coil elements, and improves cable management for advanced multi-nuclear MRI/MRS systems.

Crystallographic Evidence for Bi(I) as the Heaviest Halogen Bond Acceptor.

Complexation of the green bismuthinidene (RBi) with two equivalents of a highly fluorinated aryl iodide at low temperature allows the crystallographic identification of an unstable red species that can be regarded as an intermediate in an overall Bi(I) → Bi(III) oxidation process. Both C-I bonds are orientated toward the filled 6p orbital of bismuth (Bi-I distances 3.44-3.52 Å), leading to an elongation of the C-I bonds by 0.05 and 0.07 Å. Density functional theory (DFT) calculations confirm that the Bi(I) center is indeed acting as an electron donor, establishing two strong and directional halogen bonds. The color change from green to red upon halogen bond formation is a consequence of the energetic stabilization of a Bi(I) lone pair by interactions with the sigma-holes of the halogen bond donors. Overall, this study presents the first structural proof of bismuth, and more generally of heavy organopnictogen(I) compounds, acting as halogen bond acceptors.

Mechanism Insight into Direct Amidation Catalyzed by Zr Salts: Evidence of Zr Oxo Clusters as Active Species.

The capricious reactivity and speciation of earth-abundant metals (EAM) hinder the mechanistic understanding essential to boost their efficiency and versatility in catalysis. Moreover, metal's solution chemistry and reactivity are conventionally controlled using organic ligands, while their fundamental chemistry in operando conditions is often overlooked. However, in this study, we showcase how a better understanding of in operando conditions may result in improved catalytic reactions. By assessing the composition and structure of active species for Zr-catalyzed direct amide bond formations under operating conditions, we discovered zirconium oxo clusters form quickly and are likely active species in the reactions. Formation of these clusters dismisses the use of additional organic ligands, inert atmosphere, anhydrous solvents, or even water scavenging to provide amides in good to excellent yields. More specifically, dodeca- and hexazirconium oxo clusters (Zr12 and Zr6, respectively) rapidly form from commercial, readily available Zr salts under reaction conditions known to afford amides directly from nonactivated carboxylic acid and amine substrates. Extended X-ray absorption fine structure (EXAFS) experiments confirm the presence of oxo clusters in solution throughout the reaction, while their key role in the mechanism is supported by an in-depth computational study employing density functional theory (DFT) and molecular dynamics (MD) methods. These results underline the value of (earth-abundant) metals' intrinsic solution chemistry to transformative mechanistic understanding and to enhance the sustainability of organic transformations.

Recycling Valuable Phenol from Polycarbonate Plastic Waste Via Direct Depolymerization and Csp2-Csp3 Bond Cleavage Under Mild Conditions.

Upcycling plastic waste into commodity chemicals is recognized as an environmentally benign solution and beneficial for the sustained growth of humanity. Nevertheless, transition metal-free catalysts and energy-efficient conditions pose significant challenges due to the robust mechanical properties of plastics. Here, a strategy for selective production of phenol by upcycling polycarbonate waste via direct depolymerization and Csp2-Csp3 bond cleavage in an aqueous medium under mild conditions is reported. The commercial zeolites efficiently catalyze the depolymerization, Csp2-Csp3 bond hydrolysis, and direct Csp2-Csp3 bond scission at Cα of PC. Among all evaluated zeolites, HY (Si/Al=15) showed excellent catalytic performance, attributed to the ~75 % yield of phenol and ~15 % of acetone. The approach also employs different municipal waste PC for upcycling. Studies reveal that HY (15) exhibits high catalytic efficiency and phenol yield due to its optimum acid sites and textual properties. A scale-up experiment demonstrated that 3.1 g of phenol was produced from 5.0 g of PC, and the mass balance was 90 %. A combination of control experiments, NMR analysis, and DFT studies proposed the reaction pathway. Our findings present a sustainable avenue for upcycling PC waste and offer a new way to produce phenol, contributing to the advancement of a circular economy.

Assessing thermal resistance in fusion bond layers of 3D heterogeneous electronics packaging

We investigated thermal management challenges in semiconductor devices that use fusion bonding, with a focus on measuring the thermal resistance of the bonded interface. Starting with two fusion-bonded silicon wafers, we thinned the top wafer to below 100 μm and used frequency domain thermoreflectance to measure the effective thermal boundary resistance of the fusion bond. We established the measurement uncertainty with a multilayer thermal diffusion model, considering the effects of the top Si layer thickness and laser spot size. The thermal boundary resistance was measured to be 0.2 and 0.5 m2K/MW for two types of bonded wafers, with total SiO2 film thicknesses of 200 and 470 nm at the fusion bond layer, respectively. We also created defects at the interface and imaged these defects with the thermal phase response at specific frequencies chosen according to a thermal model. The method described can be applied to other types of wafer-to-wafer or die-to-die bonding including direct, polymeric, and metallic bonds.

DNA Replication across α-l-(3'-2')-Threofuranosyl Nucleotides Mediated by Human DNA Polymerase η.

α-l-(3'-2')-Threofuranosyl nucleic acid (TNA) pairs with itself, cross-pairs with DNA and RNA, and shows promise as a tool in synthetic genetics, diagnostics, and oligonucleotide therapeutics. We studied in vitro primer insertion and extension reactions catalyzed by human trans-lesion synthesis (TLS) DNA polymerase η (hPol η) opposite a TNA-modified template strand without and in combination with O4-alkyl thymine lesions. Across TNA-T (tT), hPol η inserted mostly dAMP and dGMP, dTMP and dCMP with lower efficiencies, followed by extension of the primer to a full-length product. hPol η inserted dAMP opposite O4-methyl and -ethyl analogs of tT, albeit with reduced efficiencies relative to tT. Crystal structures of ternary hPol η complexes with template tT and O4-methyl tT at the insertion and extension stages demonstrated that the shorter backbone and different connectivity of TNA compared to DNA (3' → 2' versus 5' → 3', respectively) result in local differences in sugar orientations, adjacent phosphate spacings, and directions of glycosidic bonds. The 3'-OH of the primer's terminal thymine was positioned at 3.4 Å on average from the α-phosphate of the incoming dNTP, consistent with insertion opposite and extension past the TNA residue by hPol η. Conversely, the crystal structure of a ternary hPol η·DNA·tTTP complex revealed that the primer's terminal 3'-OH was too distant from the tTTP α-phosphate, consistent with the inability of the polymerase to incorporate TNA. Overall, our study provides a better understanding of the tolerance of a TLS DNA polymerase vis-à-vis unnatural nucleotides in the template and as the incoming nucleoside triphosphate.

Direct Conductive Bonding of Silver Electrodes on Ultrathin Polymer Films

Direct Conductive Bonding of Silver Electrodes on Ultrathin Polymer Films

Desulfonation-associated direct amide bond formation between N-sulfonyl-1,2,3-triazoles with carboxylic acids

We have developed a highly N2-regioselective method for direct construction of amide bond from N-sulfonyl-1,2,3-triazoles and carboxylic acids in the presence of bases at 60 °C in air. The developed reaction provides the corresponding products with high yields (up to 90 %) and a broad substrate compatibility including aryl acids, heterocyclic acids, and alkyl acids. Mechanistic studies show that the reaction proceeds through a direct nucleophilic attack of N-sulfonyl-1,2,3-triazoles to carboxylate anions via a base- and water-involved synergistic desulfonation process. This work presents an unusual water-involved example for direct synthesis of amides utilizing readily available starting materials under mild conditions.

Halogen Bonding on Water─A Drop in the Ocean?

Halogen bonding is a valuable interaction in drug design, offering an unconventional way to influence affinity and selectivity by leveraging the halogen atoms' ability to form directional bonds. The present study evaluates halogen-water interactions within protein binding sites, demonstrating that targeting a water molecule via halogen bonding can in specific cases contribute beneficially to ligand binding. In solving and examining the crystal structure of 2-cyclopentyl-7-iodo-1H-indole-3-carbonitrile bound to DYRK1a kinase, we identified a notable iodine-water interaction, where water accepts a halogen bond with good geometric and energetic features. This starting point triggered further investigations into the prevalence of such interactions across various halogen-bearing ligands (chlorine, bromine, iodine) in the PDB. Using QM calculations (MP2/TZVPP), we highlight the versatility and potential benefits of such halogen-water interactions, particularly when the water molecule is a stable part of the binding site's structured environment. While the interaction energies with water are lower compared to other typical halogen bond acceptors, we deem this different binding strength essential for reducing desolvation costs. We suggest that "interstitial" water molecules, as stable parts of the binding site engaging in multiple strong interactions, could be prime targets for halogen bonding. Further systematic studies, combining high-resolution crystal structures and quantum chemistry, are required to scrutinize whether halogen bonding on water is more than a "drop in the ocean".

Terpyridine-Based Metal-Organic Cage with Enhanced Emission via Coordination-Induced Rigidity.

Realizing the regulation of photophysical properties by precisely controlling the molecular composition and configuration, thereby obtaining high-performance optical materials, remains of great significance. Due to the directionality and reversibility of the coordination bond, coordination-driven self-assembly endows the molecule with customized thermodynamically stable structures and desired properties. In this paper, a luminous metal-organic cage [Zn12L6] (S) was elaborately designed and quantitatively synthesized by self-assembly of tetrapodal TQPP chromophore-containing terpyridine ligand L with Zn2+. Complex S possessed a rigid cage-like structure, which endows a higher fluorescence quantum efficiency both in solution (∼88%) and neat solid (16%) than the corresponding ligand L. Further, using complex S as the photoactive component, two light-emitting diodes (LEDs) were successfully fabricated and the emission of pure white light (CIE coordinates: 0.3341, 0.3300) was achieved. These results afford a method to obtain enhanced luminescence performance via the formation of rigid coordination-driven supramolecular architectures.

Electric field modulated configuration and orientation of aqueous molecule chains.

Understanding how external electric fields (EFs) impact the properties of aqueous molecules is crucial for various applications in chemistry, biology, and engineering. In this paper, we present a study utilizing molecular dynamics simulation to explore how direct-current (DC) and alternative-current (AC) EFs affect hydrophobic (n-triacontane) and hydrophilic (PEG-10) oligomer chains. Through a machine learning approach, we extract a 2-dimensional free energy (FE) landscape of these molecules, revealing that electric fields modulate the FE landscape to favor stretched configurations and enhance the alignment of the chain with the electric field. Our observations indicate that DC EFs have a more prominent impact on modulation compared to AC EFs and that EFs have a stronger effect on hydrophobic chains than on hydrophilic oligomers. We analyze the orientation of water dipole moments and hydrogen bonds, finding that EFs align water molecules and induce more directional hydrogen bond networks, forming 1D water structures. This favors the stretched configuration and alignment of the studied oligomers simultaneously, as it minimizes the disruption of 1D structures. This research deepens our understanding of the mechanisms by which electric fields modulate molecular properties and could guide the broader application of EFs to control other aqueous molecules, such as proteins or biomolecules.

Prediction of Flavor Potential of Ocimum basilicum L. Side-Stream Phytoconstituents, Using Liquid Chromatography–Tandem Mass Spectrometry Analysis and In Silico Techniques

Although post-distillation side-streams of basil (Ocimum basilicum L.) pose significant economic and environmental challenges, they also bring forth new opportunities in the flavor industry. Thus, the objective of the current study was to assess the phenolic profile of basil side-stream extracts to identify key compounds and to evaluate their taste properties, using liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis, flavor prediction tools and molecular docking. In particular, 52 phytoconstituents, mainly phenolic acids, salvianolic acids, flavonoids and fatty acids derivatives, were elucidated in the side-streams of two different basil varieties (Minimum and Genovese) harvested and distilled in early and late autumn, highlighting the effect of pre-harvest factors on basil’s phenolic fingerprint. Furthermore, the results of tests undertaken using taste prediction tools showed that most of the identified compounds were very likely to taste bitter, while six of them (caffeoylferuloyltartaric acid, isoquercetin, lithospermic acid A, sagerinic acid, salvianolic acids C and F) presented a high bitterant capacity (70–90%). Moreover, according to molecular docking studies, these compounds exhibited a stronger binding affinity to the hTAS2R46 bitter receptor compared to its known agonist, strychnine. This outcome and consequently their bitterness were mainly attributed to interactions with Glu265, Thr180 and/or Trp88 through the formation of direct hydrogen bonds. Therefore, the present results provide insights into the taste profiles of basil side-streams, leading to more sustainable and innovative uses of aromatic herbs residues.