Light In Near-infrared Region Research Articles

Recent advances of photoresponsive nanomaterials for diagnosis and treatment of acute kidney injury.

Non-invasive imaging in the near-infrared region (NIR) offers enhanced tissue penetration, reduced spontaneous fluorescence of biological tissues, and improved signal-to-noise ratio (SNR), rendering it more suitable for in vivo deep tissue imaging. In recent years, a plethora of NIR photoresponsive materials have been employed for disease diagnosis, particularly acute kidney injury (AKI). These encompass inorganic nonmetallic materials such as carbon (C), silicon (Si), phosphorus (P), and upconversion nanoparticles (UCNPs); precious metal nanoparticles like gold and silver; as well as small molecule and organic semiconductor polymer nanoparticles with near infrared responsiveness. These materials enable effective therapy triggered by NIR light and serve as valuable tools for monitoring AKI in living systems. The review provides a concise overview of the current state and pathological characteristics of AKI, followed by an exploration of the application of nanomaterials and photoresponsive nanomaterials in AKI. Finally, it presents the design challenges and prospects associated with NIR photoresponsive materials in AKI.

Mechanical and electrical properties of α-MoO3 belts under strain for flexible electronics applications

This study investigated a straightforward and cost-effective method for synthesizing α-MoO3 belts and evaluated their potential as substrates for flexible electronic devices. Transparent α-MoO3 belts, featuring millimeter-scale side lengths and micrometer-scale thicknesses, were produced through a one-step sintering process using metallic molybdenum powder. When affixed to stretchable substrates, the α-MoO3 belts demonstrated robust mechanical stability under continuous and sustained tensile strain in the longitudinal direction. The belts exhibited a transmittance exceeding 68 % in the visible and near-infrared light regions. The current between gold dots on belts fixed to a stretchable polydimethylsiloxane substrate increased with the application of tensile strain. Furthermore, a CoFe2O4 thin film deposited at elevated temperature onto an α-MoO3 belt exhibited significant magnetic anisotropy. These findings introduce a novel and efficient approach for fabricating highly crystalline thin films on stretchable and bendable substrates using α-MoO3 belts.

Growth and characterization of Sb2(SxSe1-x)3 thin films prepared by chemical-molecular beam deposition for solar cell applications

Antimony sulfide selenide, Sb2(SxSe1-x)3 (x = 0–1), is a tunable bandgap compound that combines the advantages of antimony sulfide (Sb2S3) and antimony selenide (Sb2Se3). This material shows great potential as a light-absorbing material for low-cost, low-toxicity, and highly stable thin-film solar cells. In this study, Sb2(SxSe1-x)3 thin films were deposited by chemical-molecular beam deposition on soda-lime glass substrates using antimony (Sb), selenium (Se), and sulfur (S) precursors at a substrate temperature of 420 °C. By independently controlling the source temperatures of Sb, Se, and S, Sb2(SxSe1-x)3 thin films with varying component ratios were obtained. Scanning electron microscopy revealed significant changes in the surface morphology of the films depending on the elemental ratio of [S]/([S]+[Se]). Crystallites shaped like cylindrical microrods with d = 0.5–2 µm diameter and l = 3–5 µm length were grown at a certain angle on the substrate. X-ray diffraction patterns showed peaks corresponding to the orthorhombic structures of Sb2Se3, Sb2S3 and their ternary compounds Sb2(SxSe1-x)3. The optical characterization revealed a high absorption coefficient of 105 cm−1 in the visible and near-infrared light regions. The band gap of the compounds changed almost linearly from 1.2 eV to 1.36 eV with a change in the ratio of elements [S]/([S]+[Se]) from 0.03 to 0.08.

Graphene with suitable-size nitrogen-doped cavity being an excellent photocatalyst for proton-coupled electron transfer in water splitting

Aiming to attain porous carbon nitride photocatalysts with high specific surface area, abundant active sites, broad absorption range and effective electron-hole separation, we remove carbon rings from graphene and replace all the edge carbon atoms of the cavity with nitrogen atoms. The accurate electronic structures and exciton properties of the proposed materials are revealed by the ab initio many-body Green's function theory. Computational results show that the absorption of the designed materials can cover both the visible and the near-infrared light region. The exciton binding energies of the materials are one order of magnitude lower than those of the typical two-dimensional photocatalyst graphitic carbon nitride. Due to the formation of hydrogen bonds between pyridinic nitrogen atoms and water molecules during water splitting, the key excited-state proton-coupled electron transfer reactions are barrierless. These findings could serve as guidelines for the realization of high-performance metal-free two-dimensional photocatalysts.

Ag nanoparticle-mediated LSPR effect and electron transfer for enhanced oxidative degradation process of g-C3N5 nanoflowers

The design of photocatalytic system with broad-spectrum response to sunlight and rapid electron transfer is critical for efficient destruction of diverse contaminants in various environmental situations. Herein, self-assembled supramolecular strategy was employed to anchor Ag nanoparticles on the nanoflower-like g-C3N5 surface to construct Schottky-type catalyst (ACN-1) for efficient degradation of organic contaminants. The localized surface plasmon resonance (LSPR) effect significantly improves photocatalytic activity of materials by boosting rapid transfer of interlayer energy and photogenerated electrons and extending the absorption edge of catalysts into near-infrared light region. In actual water samples, ACN-1 entirely eliminated tetracycline (k = 1.0787 min−1) within 40 min and maintained high degradation rate (more than 80 %) under various water quality parameters. Furthermore, ACN-1 demonstrated remarkable suitability to microcystin-LR (98.9 %, k = 0.08098 min−1), sulfamethoxazole (81.2 %, k = 0.02984 min−1), and methylene blue (91.4 %, k = 0.04072 min−1). Quenching experiments and ESR tests showed that main active species in system were 1O2, •O2−, and h+. Finally, five photodegradation pathways and 26 intermediates of TC were elucidated by combining ESR signals, LC-MS and Fukui index. After photodegradation treatment, the toxicity of solution was drastically reduced and the mineralization reached 62.48 %. This study provides new insights into the design and interaction mechanisms of novel g-C3N5-based catalysts and effectively contributes to remediation strategies for emerging pollutants in water.

Phase junction CdS decorated by plasmonic Cu1.8S: Realizing directed carriers transfer path and broad solar light-response for efficient photocatalytic water splitting

Phase engineering is an emerging strategy for tuning the electronic structure by manipulating atomic configuration and accumulating the carrier transfer, making it important in the field of photocatalysis. In this paper, Cu1.8S@phase junction CdS is successfully synthesized. Phase junction CdS (HCC) exhibits band bending to optimize the separation and transfer of photogenerated carriers. The introduction of plasmonic Cu1.8S not only endows CdS with a broad photoresponse ability to the near-infrared (NIR) light region and a photothermal effect but also forms the p-n junction to further accelerate the carrier separation rate. The synergistic effect of phase junction and p-n junction realizes an excellent photocatalytic hydrogen activity in the full spectrum. Cu1.8S@HCC exhibits an H2 production rate of 3.7 mmol·g−1·h−1 and 374 μmol·g−1·h−1 under Visible (Vis)-light (780 ≥ λ ≥ 420 nm) and NIR light (λ ≥ 780 nm) illumination, which is 31 times and 9 times higher than the Vis-light driven photocatalytic H2 rate of cubic CdS and HCC. Importantly, through detailed characterization and density functional theory (DFT) calculations, the migration pathway of charge carriers and the reactive active site in multiple interfaces are determined. This work presents an exploitation of advanced photocatalysts in multiple phases for excellent solar energy conversion.

A 700nm LED Light Activated Ru(II) Complex Destroys Tumor Cytoskeleton via Photosensitization and Photocatalysis.

Photoactivable chemotherapy (PACT) using metallic complexes provides spatiotemporal selectivity over drug activation for targeted anticancer therapy. However, the poor absorption in near-infrared (NIR) light region of most metallic complexes renders tissue penetration challenging. Herein, an NIR light triggered dinuclear photoactivable Ru(II) complex (Ru2) is presented and the antitumor mechanism is comprehensively investigated. The introduction of a donor-acceptor-donor (D-A-D) linker greatly enhances the intramolecular charge transition, resulting in a high molar extinction coefficient in the NIR region with an extended triplet excited state lifetime. Most importantly, when activated by 700nm NIR light, Ru2 exhibits unique slow photodissociation kinetics that facilitates synergistic photosensitization and photocatalytic activity to destroy diverse intracellular biomolecules. In vitro and in vivo experiments show that when activated by 700nm NIR light, Ru2 exhibits nanomolar photocytotoxicity toward 4T1 cancer cells via the induction of calcium overload and endoplasmic reticulum (ER) stress. These findings provide a robust foundation for the development of NIR-activated Ru(II) PACT complexes for phototherapeutic application.

Ligand-engineered Cu-based halide perovskite for highly efficient near-infrared photocatalytic CO2 reduction

A key challenge in harvesting solar energy for efficient chemical conversion is the lack of photocatalysts with wide activation wavelengths. Herein, we propose for the first time to utilize halide perovskite to absorb the full spectrum (200–2500 nm), including ultraviolet (UV), visible (Vis), and near-infrared (NIR) light, to directly power photocatalytic CO2 reduction. This full-spectrum light-responsive occurs on metal halide perovskite Cs2CuCl4 microcrystals (MCs), and the ligand soybean lecithin is applied to optimize the active phase of Cs2CuCl4 photocatalyst, such as morphology, particle size, crystal face and electronic structure. As revealed by optical absorption analysis, the Cs2CuCl4 and ligand soybean lecithin modified Cs2CuCl4 (SL-Cs2CuCl4) MCs exhibit significant optical absorption in the UV, Vis light and NIR light regions. The photocatalytic CO2 reduction performance was assessed under simulated sunlight (200–2500 nm), and the SL-Cs2CuCl4 MCs achieved a CO fuel yield of 254.46 µmol g−1, which increased the yield by 5 times relative to the initial sample. Based on in-situ Fourier transform infrared, electron spin resonance and X-ray photoelectron spectroscopy, the active substances and reaction intermediates at the active site of SL-Cs2CuCl4 MCs were dynamically monitored, and the photocatalytic mechanism was revealed together with density functional theory (DFT) calculations. The DFT calculation shows that the photocatalytic reduction of CO2 to CO by Cs2CuCl4 is proposed to involve the concerted action of both Cs and Cu sites.

Unveiling the potentiality of a self-powered CGT chalcopyrite-based photodetector: theoretical insights

The article demonstrates the design and modelling of CuGaTe2 direct bandgap (1.18 eV) chalcopyrite-based photodetector (PD), which has superb optical and electronic characteristics and shows remarkable performance on the photodetector. The photodetector has been investigated throughout the work by switching width, carrier and defect densities of particular layers and also the interface defect density of particular interfaces. The various layers have been optimized for the higher performance of the PD. Also, the impression of various device resistances has been analyzed. The JSC and VOC of the heterostructure photodetector is found to be 38.27 mA/cm2 and 0.94 V, in turn. The maximum responsivity, R and detectivity, D* are found to be 0.663A/W and 1.367 × 1016 Jones at a wavelength of 920 nm. The spectral response has a very high value in the range of 800 to 1000 nm light wavelength, which confirmed that this device is capable of detecting the near infrared (NIR) region of light. This work gives important guidance for the manufacture of CGT material-based photodetectors with higher performance.

Efficient tunable visible and near-infrared emission in Sb3+/Sm3+-codoped Cs2NaLuCl6 for near-infrared light-emitting diode, triple-mode fluorescence anti-counterfeiting and information encryption

Rare earth ions (RE3+)-doped double perovskites have attracted tremendous attention for its fascinating optical properties. Nevertheless, RE3+ generally exhibits poor photoluminescence quantum yield (PLQY) for their parity-forbidden 4f-4f transition and the low doping concentration. Herein, we reported Sb3+/Sm3+-codoped rare earth-based double perovskite Cs2NaLuCl6 that enables efficient visible and near-infrared (NIR) emission, which stems from self-trapped exciton (STE) and Sm3+, respectively. Benefit from up to 72.89% energy transfer efficiency from STE to Sm3+ and high doping concentrations due to similar ionic activity between Sm3+ and Lu3+, thus eruptive PLQY of 74.58% in the visible light region and 23.12% in the NIR light region can be obtained. Moreover, Sb3+/Sm3+-codoped Cs2NaLuCl6 exhibits tunable emission characteristic in the visible light region under different excitation wavelengths, which can change from blue emission (254 nm excitation) to white emission (365 nm excitation). More particularly, only the NIR emission can be captured by the NIR camera when a 700 nm cutoff filter is added. The excellent stability and unique optical properties of Sb3+/Sm3+-codoped Cs2NaLuCl6 enable us to demonstrate its applications in NIR light-emitting diode, triple-mode fluorescence anti-counterfeiting and information encryption. These findings provide new inspiration for the application of rare earth-based double perovskite in optoelectronic devices.

Self-powered polarization-sensitive photodetection and imaging based on Sb[formula omitted]Se[formula omitted] microbelt/Si van der Waals heterojunction with MXene transmittance window

Polarization-sensitive detection and imaging have many significant applications in target recognition, optical switches, industrial inspection, and so on. Herein, on-chip near-infrared photodetectors based on individual Sb2Se3 microbelt/Si van der Waals heterojunction with MXene transmittance window were designed. The fabricated Sb2Se3 microbelt/Si photodetector displays a broad spectral response that spans the visible to near-infrared light regions, as well as a peak photoresponse at a wavelength of 1000 nm. The optimized Sb2Se3 microbelt/Si photodetector exhibits excellent photovoltaic performance with an ultralow dark current of 10 pA, a high responsivity of 25 mA/W, a favorable detectivity of 1010 Jones, a fast response time of 1.7 ms/2.9 ms under near-infrared illumination with power density of 0.1 mW/cm2. The identified performance can be attributed to the heterojunction’s type-II band configuration, making it suited for the quick separation of photo-generated carriers. More importantly, polarization-sensitive photodetectors with an anisotropy ratio of 1.21 to 1.28 under the illumination of 940 nm light can be achieved. The Sb2Se3 microbelt/Si photodetector also demonstrates high-resolution single-pixel polarimetric imaging at zero bias. This work demonstrates an effective strategy for using anisotropic/isotropic Sb2Se3 microbelt/Si van der Waals heterojunction to realize high-performance, self-powered, and polarization-sensitive detection and imaging.

A temperature and electric field responsive flexible hybrid composite film containing CsxWO3 nanocrystals for energy efficient smart window

Smart windows, which can dynamically adjust solar radiation transmittance in accordance with people's requirements and the ambient temperatures, play an important role in solving the problem of energy consumption in buildings. However, the polymer-dispersed liquid crystals, one of the representatives of smart window, are generally only optically modulated in the visible region, but not sensitive to the near-infrared light region, which has a thermal effect. Herein, we reported a hybrid composite film with both light and heat management by introducing inorganic CsxWO3 nanocrystals into the organic PDLC system. The optical modulation effect of this film covers the solar irradiation in the range of 400–2500 nm, including visible light and invisible near-infrared light. In addition, the optical state of the film could be switched between transparent and opaque by electric field when the temperature was below the phase transition temperature (45 °C), while the film remained transparent when the temperature was above the phase transition temperature. Simultaneously, about 60% to 95% of the NIR irradiation range of 800–2500 nm can be screened under the variations of the thermal and electric fields due to the local surface plasmon resonance of the CsxWO3 nanocrystals. The thermal insulation effect demonstrated by the model house fitted with this film gives it the potential to be used in energy-efficient smart windows.

Fluorescence Tracking of Small Extracellular Vesicles In Vivo.

In this study, we employed organic and inorganic dyes that have fluorescence under visible or near-infrared light region to stain human umbilical cord (Huc) mesenchymal stem cell (MSC)-, HEK293T cell- and HGC cell-derived small extracellular vesicles (sEVs), and then tracked their fluorescence signals in human gastric cancer xenografted murine models. Several biological characteristics were examined and compared when different dye-stained sEVs in the same tumor model or the same dye-stained sEVs between different tumor models were applied, including sEVs circulation in the blood, biodistribution of sEVs in major organs, and time-dependent tumor accumulation of sEVs. The results demonstrated that distinct tumor accumulation features were presented by sEVs if labeled by different fluorescent dyes, while sEVs derived from different cell lines showed homologous blood circulation and tumor accumulation. To conclude, although fluorescence imaging remains a reliable way to trace sEVs, single staining of sEVs membrane should be obviated in future work when examining the biological fate of sEVs.

A Review on Multiple I-III-VI Quantum Dots: Preparation and Enhanced Luminescence Properties.

I-III-VI type QDs have unique optoelectronic properties such as low toxicity, tunable bandgaps, large Stokes shifts and a long photoluminescence lifetime, and their emission range can be continuously tuned in the visible to near-infrared light region by changing their chemical composition. Moreover, they can avoid the use of heavy metal elements such as Cd, Hg and Pb and highly toxic anions, i.e., Se, Te, P and As. These advantages make them promising candidates to replace traditional binary QDs in applications such as light-emitting diodes, solar cells, photodetectors, bioimaging fields, etc. Compared with binary QDs, multiple QDs contain many different types of metal ions. Therefore, the problem of different reaction rates between the metal ions arises, causing more defects inside the crystal and poor fluorescence properties of QDs, which can be effectively improved by doping metal ions (Zn2+, Mn2+ and Cu+) or surface coating. In this review, the luminous mechanism of I-III-VI type QDs based on their structure and composition is introduced. Meanwhile, we focus on the various synthesis methods and improvement strategies like metal ion doping and surface coating from recent years. The primary applications in the field of optoelectronics are also summarized. Finally, a perspective on the challenges and future perspectives of I-III-VI type QDs is proposed as well.

Synthesis and evaluation of curcumin-based near-infrared fluorescent probes for detection of amyloid β peptide in Alzheimer mouse models

The abnormal accumulation of amyloid β protein (Aβ) is one of the most important causes of Alzheimer's disease (AD) and is usually a detecting biomarker. Curcumin and its derivatives have potential Aβ aggregate targeting ability; we synthesized a series of curcumin-based near-infrared fluorescence probes in this study. By characterizing the excitation wavelength and emission wavelength, the imaging characteristics of the investigation in the near-infrared light region were determined; with an increase in the concentration of the probe compounds, the fluorescence intensity showed an upward trend, demonstrating ideal optical characteristics. In vivo, imaging results showed that the synthesized probe compounds could penetrate the blood–brain barrier (BBB) and specifically bind to Aβ in the brain of APP/PS1 mice. Especially for compound 3b, the maximum emission wavelength was around 667 nm, and the fluorescence signal intensity in the brain of the APP/PS1 mice model was more than twice that of the wild control group at 120 min after administration, which could display Aβ pathological changes. The fluorescent probes designed in this study can become an effective tool for early AD diagnosis and visual detection.

Polarization-sensitive near-infrared photodetectors based on quasi-one-dimensional Sb2Se3 nanotubes

In this work, we study the chemical vapor deposition growth of Sb2Se3 nanotubes and investigate their novel applications in polarization-sensitive near-infrared photodetectors. The grown Sb2Se3 nanotubes present a high crystal quality with an average length of 23.96 µm, an average width of 0.99 µm, and an average height of 315 nm. The fabricated singular Sb2Se3 nanotube-based photodetector exhibits a wide spectral response, ranging from visible to near-infrared light regions (400–980 nm), as well as a peak photo-response under the illumination of near-infrared (830 nm) light. At room temperature and standard atmospheric pressure, the Sb2Se3 nanotube photodetector presents a large photocurrent on/off ratio of 364, a high responsivity of 4.39 A W−1, a good specific detectivity of 9.63 × 1010 Jones, and a high external quantum efficiency of 655% under the illumination of 830 nm light. The identified performance can be attributed to intrinsic characteristics of this compound coupled with a highly uniform Sb2Se3 nanotube crystalline structure. The Sb2Se3 nanotube photodetector also exhibits excellent stability after> 200 photo-switching cycles. Most notably, the Sb2Se3 nanotube photodetector presents a large linear dichroic ratio of 3.95 under the illumination of 830 nm light, revealing its great potential in near-infrared polarized photodetection applications.

High-performance multiple-doped In2O3 transparent conductive oxide films in near-infrared light region

High-quality W, Mo, Ti, Zr, and Ga-doped indium oxide (multiple-doped In2O3) films are deposited at room temperature by direct current magnetron sputtering process under different oxygen proportion, with 200 °C annealing. A maximum Hall mobility of 71.6 cm2 V−1 s−1 is obtained at a middle oxygen proportion of 2%, thanks to the reduction of impurity scattering center, which is nearly three times higher than an ITO film of 23.6 cm2 V−1 s−1. The multiple-doped In2O3 films showed a remarkable 30% improvement of the optical transmittance (>80%) in the near-infrared (NIR) region compared to the ITO film (about 60%), which is mainly attributed to the decrement of free carrier absorption due to low carrier concentration (<2 × 1020 cm−3), an order magnitude lower than the ITO film (1.56 × 1021 cm−3). Additionally, x-ray diffraction results confirm that the films have a polycrystalline structure with preferential orientation growth in the <100> direction. In the NIR region, the multiple-doped In2O3 films have a superior figure of merit of 5.02 × 10−3 Ω−1, which is an order magnitude higher than the ITO film (5.31 × 10−4 Ω−1). This work reports a new In2O3-based material with both high electrical and optical performance, which is suitable for the application of advanced optoelectronic devices.

Theoretical study on a series of naphthalimide-contained two-photon fluorescent hypochlorite probe targeting endoplasmic reticulum: response mechanism and receptor effect.

The development of detecting hypochlorous acid (HClO) in living endoplasmic reticulum has attracted much attention in the fields of biology, medicine, and pharmacy. In the present work, the one-photon absorption (OPA), one-photon emission (OPE), and two-photon absorption (TPA) properties of a series newly synthesized chemosensors with naphthalimide as the fluorophore were systematically investigated using time-dependent density functional theory in combination with response theory. Special emphasis is placed on evolution of the probes' optical properties in the presence of HClO. These compounds show drastic changes in their photoabsorption and photoemission properties when they react with HClO, indicating them to be excellent candidates as fluorescent chemosensors. To further understand the mechanisms of the two probes, we have employed the hole and electron analysis to investigate the charge transfer process for the photoemission of the molecules. The receptor effect is found to play a dominant role in the sensing performance of these probes. Specifically, two-photon absorption properties of the molecules are calculated. We have found that all probes show significant two-photon responses in the near-infrared light region. And the maximum two-photon absorption cross section of probe 2 is greatly enhanced with the presence of HClO, indicating that probe 2 can act as a potential two-photon excited fluorescent HClO probe. The theoretical investigations would be helpful to build the structure-property relationships for the naphthalimide-contained probes, providing information on the design of efficient two-photon fluorescent sensors that can be used for biological imaging of HClO in endoplasmic reticulum.

Light to heat conversion efficiency of single-walled carbon nanotubes

Semiconducting single-walled carbon nanotubes (s-SWCNTs) have the potential as light to heat efficiency, recently known as photothermal conversion efficiency , for photothermal therapeutic applications since they exhibit strong absorption in the near-infrared region (NIR). We report experimental studies of light to heat efficiency of two classes of s-SWCNTs, including double chiralities (DC) and many chiralities (MC) of s-SWCNTs. The was obtained by using the results from the experimental heating of s-SWCNTs with NIR light at 808 nm. Interestingly, the of MC s-SWCNTs was 1.88-fold higher than DC s-SWCNTs, which leads to a 19% decrease in the heating rate of DC compared to the heating rate of MC s-SWCNTs. This study demonstrates that chirality dependence is an essential metric in the heating rate of s-SWCNTs and provides a validated framework to compare the heating capabilities between DC and MC.

An Approach to Developing Cyanines with Upconverted Photosensitive Efficiency Enhancement for Highly Efficient NIR Tumor Phototheranostics.

Upconverted reactive oxygen species (ROS) photosensitization with one-photon excitation mode is a promising tactic to elongate the excitation wavelengths of photosensitive dyes to near-infrared (NIR) light region without the requirement of coherent high-intensity light sources. However, the photosensitization efficiencies are still finite by the unilateral improvement of excited-state intersystem crossing (ISC) via heavy-atom-effect, since the upconverted efficiency also plays a decisive role in upconverted photosensitization. Herein, a NIR light initiated one-photon upconversion heavy-atom-free small molecule system is reported. The meso-rotatable anthracene in pentamethine cyanine (Cy5) is demonstrated to enrich the populations in high vibrational-rotational energy levels and subsequently improve the hot-band absorption (HBA) efficiency. Moreover, the spin-orbit charge transfer intersystem crossing (SOCT-ISC) caused by electron donated anthracene can further amplify the triplet yield. Benefiting from the above two aspects, the 1 O2 generation significantly increases with over 2-fold improved performance compared with heavy-atom-modified method under upconverted light excitation, which obtains efficient in vivo phototheranostic results and provides new opportunities for other applications such as photocatalysis and fine chemical synthesis.