Stepwise Substitution Research Articles

Expression of influenza A H1N1 and H3N2 viruses Mosaic-HA1 antigens and evaluation of its immunogenicity in mice

Vaccination is the most effective measure for reducing and preventing influenza and related complications. In this study, we analyzed the mutation trend and the antigen dominant site changes of the amino acid sequence of hemagglutinin subunit 1 (HA1) of human influenza A virus (IAV) in the northern hemisphere from 2012 to 2022. According to the HA1 sequences of A/Darwin/6/2021 (H3N2) and A/Wisconsin/588/2019 (H1N1) recommended by the World Health Organization in the 2022 influenza season in northern hemisphere, we employed the mosaic algorithm to design three Mosaic-HA1 antigens through stepwise substitution. Mosaic-HA1 was expressed and purified in 293F cells and then mixed with the alum adjuvant at a volume ratio of 1:1. The mixture was used to immunize BALB/c mice, and the immunogenicity was evaluated. Enzyme-linked immunosorbent assay showed that Mosaic-HA1 induced the production of IgG targeting two types of HA1, the specific IgG titers for binding to H3 protein and H1 protein reached 105 and 103 respectively. The challenge test showed that Mosaic-HA1 protected mice from H3N2 or H1N1. This study designs the vaccines by recombination of major antigenic sites in different subtypes of IAV, giving new insights into the development of multivalent subunit vaccines against influenza.

Facile Access to Phosphorus Ylide-fused Heteroarenes Possessing Tunable Optoelectronic Properties and High Nonlinear Optical Performances.

We report here a novel family of ylidic P-heteroarenes (P1-P6), structurally featuring unique phosphonium cyclopentadienylide (P-Cp)-fused π-skeletons and synthetically prepared via an unexpected one-pot [2+3]/[3+3] phospha-annulation reaction. While the facile and modular synthesis allows the fine-tuning of their optical absorptions and redox properties, single-crystallographic and theoretical analysis of these P-heteroarenes further reveal that the fusion of P-Cp moiety leads to substantial intramolecular charge-separated features with high ylidic character values of up to 84 %. Benefitted from such dipolar structures, these P-heteroarenes not only allows stepwise electrophilic substitution reaction for further structural π-expansions, but also exhibit excellent nonlinear optical (NLO) responses and optical limiting (OL) performances comparable to or exceed those of C60. As a model compound, the persistent radical-anion salt of P5a was also prepared through chemical reduction, thus offering valuable insights into the electronic structures of reduced P-ylidic species. Our work not only established a highly efficient synthetic method toward new P-heteroarenes, but also provide fundamental understanding of those fused-ring ylidic P-heterocycles with promising NLO/OL applications.

Facile Access to Phosphorus Ylide‐fused Heteroarenes Possessing Tunable Optoelectronic Properties and High Nonlinear Optical Performances

AbstractWe report here a novel family of ylidic P‐heteroarenes (P1–P6), structurally featuring unique phosphonium cyclopentadienylide (P−Cp)‐fused π‐skeletons and synthetically prepared via an unexpected one‐pot [2+3]/[3+3] phospha‐annulation reaction. While the facile and modular synthesis allows the fine‐tuning of their optical absorptions and redox properties, single‐crystallographic and theoretical analysis of these P‐heteroarenes further reveal that the fusion of P−Cp moiety leads to substantial intramolecular charge‐separated features with high ylidic character values of up to 84 %. Benefitted from such dipolar structures, these P‐heteroarenes not only allows stepwise electrophilic substitution reaction for further structural π‐expansions, but also exhibit excellent nonlinear optical (NLO) responses and optical limiting (OL) performances comparable to or exceed those of C60. As a model compound, the persistent radical‐anion salt of P5a was also prepared through chemical reduction, thus offering valuable insights into the electronic structures of reduced P‐ylidic species. Our work not only established a highly efficient synthetic method toward new P‐heteroarenes, but also provide fundamental understanding of those fused‐ring ylidic P‐heterocycles with promising NLO/OL applications.

2-(Butylamino)-6-chloro-4-[3-(7-chloro-4-quinolylamino)propylamino]-1,3,5-triazine

We herein report the synthesis of a 7-chloro-aminoquinoline triazine conjugate. The s-triazine library was generated by stepwise nucleophilic substitution of cyanuric chloride with butylamine. The structure of the compound was comprehensively determined using various analytical techniques, including proton nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR), heteronuclear single quantum coherence (HSQC), and Distortionless Enhancement by Polarization Transfer (DEPT-135) experiments. Additionally, ultraviolet (UV) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and high-resolution mass spectrometry (HRMS) were employed for full characterization. Preliminary studies explored the potential interaction of the molecule with dihydrofolate reductase (DHFR) using molecular modeling. Furthermore, its drug-likeness was assessed by predicting relevant pharmacokinetic properties.

Abstract A035: Mutation of NOTCH1 is selected within normal esophageal tissues, yet leads to selective epistasis suppressive of further evolution into cancer

Abstract Sequencing of tissues from histologically normal esophagus, among other organs, has revealed that normal tissues acquire somatic variants that are also found in cancers arising from the same tissue types. Our understanding of how somatic mutations that are commonly found in normal tissue can contribute to tumorigenesis is limited: common somatic mutations may or may not confer phenotypes compatible with oncogenesis. However, the strength of selection for somatic variants that appear in both normal and cancer tissues can be quantified in each context using evolutionary modeling approaches. We studied the evolutionary trajectory from normal esophageal tissue to esophageal squamous-cell carcinoma (ESCC) by analysis of sequencing data from previous studies on normal esophageal epithelium and ESCC to reveal the stepwise contributions of somatic mutations to increased cellular division and survival. We also analyzed pairwise selective epistasis between somatically mutated genes that may lead to stepwise substitution patterns. We found that NOTCH1 substitutions are at high prevalence in normal tissue, and scaled selection coefficients indicate that NOTCH1 mutations are highly selected in normal esophageal tissue. In contrast, there is little to no positive selection for NOTCH1 mutations in ESCC, suggesting that NOTCH1 substitutions do not drive tumorigenesis. Indeed, NOTCH1 mutations have recently been shown to favor clonal expansion in normal esophageal tissue. Furthermore, we calculate that mutations in NOTCH1 exhibit antagonistic epistasis with well-known cancer drivers, including TP53, reducing selection for progressive mutations in tumorigenesis. This antagonistic epistasis likely underlies the low likelihood of tumor progression in the presence of NOTCH1 mutations in the esophagus. Citation Format: Kira A. Glasmacher, Vincent L. Cannataro, Jeffrey D. Mandell, Mia Jackson, J. Nic Fisk, Jeffrey P. Townsend. Mutation of NOTCH1 is selected within normal esophageal tissues, yet leads to selective epistasis suppressive of further evolution into cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A035.

Site dependent strategy for B/C/N homo and heteroatom co-doping in governing the optoelectronic behavior of MgO monolayers

Density functional theory calculations are carried out to investigate the effects of homo- and hetero-type co-doping of B, C and N on structural and electronic properties of MgO monolayers (MLs). The co-doping sites considered here are the possible equivalent and non-equivalent positions of a hexagon in a pristine MgO ML. The planarity of the monolayers is found to be governed by the site selectivity of the dopant atoms as well as the positions of doping. Planar monolayers have a higher likelihood of formation than the non-planar monolayers. In case of non-equivalent doping, the doping atoms always prefer positions that are closer. Stepwise substitution is more likely to occur than simultaneous substitution in formation of the co-doped monolayers. Most of the co-doping combinations introduce magnetism to the pristine MgO ML. Hetero-type monolayers prefer to be in magnetic states and even exhibit higher magnetic moments than homo-type MLs, with a maximum value of 4 μB for B–N co-doping. Almost all the monolayers are semiconducting with significantly reduced band gaps, while few hetero-type monolayers are metallic in nature. The electronic energy band gaps of the monolayers are compatible with the IR and visible regions of the electromagnetic spectrum. The overall tuning of the electronic properties renders the co-doped MgO monolayers effective for applications in spintronics and optoelectronics.

Advancing energy safety via stepwise nucleophilic substitution on tetrazine

This study presents a feasible approach to synthesizing hydrazine/nitroamine and amino/nitroamine substituted tetrazine derivatives.

Liking and Description of Pasta Sauces with Varying Mealworm Content.

Entomophagy is directly connected with culture, explaining why it is commonly rejected in Western countries. Due to increased meat consumption in recent years with its associated negative impacts on health and sustainability, the development of products based on alternative protein sources has become urgent. The larval form of Tenebrio molitor (mealworm) has the potential to substitute meat as it requires less resources and produces less emissions compared to other forms of meat production. Therefore, in this project we have aimed to develop pasta sauces with differing mealworm contents based on a common meat sauce and to test the acceptance with 91 consumers in Austria. Three sauces (100% mealworm, 50% mealworm and 50% meat, 100% meat) were developed and tested using a 9-point hedonic scale for acceptance, and the CATA (Check-All-That-Apply) method was integrated to also receive descriptive information. The analysis of the liking data revealed that the liking for the hybrid sauce with meat and mealworm content was comparable to the meat sauce (6.9 ± 1.8. vs. 6.5 ± 1.8, p > 0.05). Less liked was the sauce with the highest mealworm content (5.7 ± 1.8, p < 0.05). The CATA analysis demonstrated the strongest positive effects on the mean in terms of how much the products were liked for the attribute "fleshy" (0.8). On the other hand, the attributes "brownish" (-0.9) or "mushy" (-1.0) had the strongest negative effects on the mean of the liking of products. We have seen that meat cannot be substituted by mealworm immediately and completely. The results suggest a stepwise substitution and the further adaptation of products regarding the (negative and positive effecting) attributes to increase consumer acceptance.

Interaction of the Bipyridyl Gold(III) Complex with Anions of Thiol-Containing Acids in Aqueous Solution

The equilibria of stepwise substitution Au(bipy)+ OH– = Au(bipy)ClOH+ + Cl– and Au(bipy)+ 2OH– = Au(bipy)+ 2Cl– in aqueous solution at T = 25°C and I = 0.2 M (NaCl), log β1 = 9.22, log β2 = 16.61 have been studied. For bipyridyl complexes Au(bipy)(X = Cl, OH) at pH 2.0 and 7.4, redox interactions with anions of thiol-containing acids (glutathione, cysteine, thiomalate) have been studied. In all cases, at the initial stage, a rapid reduction of gold(III) to gold(I) was observed with the simultaneous release of bipyridyl. A detailed analysis of UV spectra showed that the main products of gold(III) reduction are highly stable gold(I) thiolate complexes. The presence of further slower steps depends on the initial ratio of thiol to gold.

Pleistocene aragonite crust diagenesis mimics microbialite fabrics (Danakil Depression, Ethiopia)

Fibrous aragonite crusts occur in two consecutive Pleistocene successions in the Danakil Depression (Afar, Ethiopia). Lateral transitions between pristine and altered fibrous aragonite crusts document changes in texture associated with diagenesis. Crusts formed as essentially abiotic seafloor precipitates at the transition from marine to evaporitic conditions. Diagenesis started with the dissolution of aragonite fans at the interface between single fans in non-laminated crusts and along lamination planes in isopachous, irregular, or crudely laminated crusts. Incomplete dissolution resulted in the development of secondary porosity within a matrix of undissolved aragonite fibers. Subsequently, the porosity was filled with calcite that systematically encased remaining aragonite crystals. This was followed by the dissolution of remnant aragonite fibers, producing a network of elongated inter- and intracrystalline pores that were eventually filled with low-Mg calcite. The stepwise substitution of fibrous aragonite by low-Mg calcite resulted in sparry, sparry-cloudy, sparry-micritic (including clotted micrite), and peloidal textures, which obscure the fibrous nature of the original deposits. Stable C- and O-isotope compositions suggest that early diagenesis was driven by meteoric and evaporative fluids. These observations unequivocally demonstrate destructive diagenesis, resulting in secondary textures, which mimic micritic and grumous (peloidal and clotted) textures associated with sparry microfabrics.This suggests that these textures, classically interpreted as primary microbial precipitates and used as evidence of biogenicity in ancient microbialites, might be diagenetic products in some cases, even though at some stage, microbial processes and/or degradation of organic matter could have been involved in the diagenetic process.

Ionic mononuclear [Fe] and heterodinuclear [Fe,Ru] bis(diphenylphosphino)alkane complexes: Synthesis, spectroscopy, DFT structures, cytotoxicity, and biomolecular interactions

Iron(II) and Ru(II) half-sandwich compounds encompass some promising pre-clinical anticancer agents whose efficacy may be tuned by structural modification of the coordinated ligands. Here, we combine two such bioactive metal centres in cationic bis(diphenylphosphino)alkane-bridged heterodinuclear [Fe2+, Ru2+] complexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(η5–C5H5)Fe(CO)2(κ1–PPh2(CH2)nPPh2)]{PF6} (n = 1–5), compounds 1–5, and heterodinuclear [Fe2+, Ru2+] complexes, [(η5–C5H5)Fe(CO)2(μ–PPh2(CH2)nPPh2))(η6–p–cymene)RuCl2]{PF6} (n = 2–5) (compounds 7–10), were synthesized and characterised. The mononuclear complexes were moderately cytotoxic against two ovarian cancer cell lines (A2780 and cisplatin resistant A2780cis) with IC50 values ranging from 2.3 ± 0.5 μM to 9.0 ± 1.4 μM. For 7–10, the cytotoxicity increased with increasing Fe⋅⋅⋅Ru distance, consistent with their DNA affinity. UV–visible spectroscopy suggested the chloride ligands in heterodinuclear 8–10 undergo stepwise substitution by water on the timescale of the DNA interaction experiments, probably affording the species [RuCl(OH2)(η6-p-cymene)(PRPh2)]2+ and [Ru(OH)(OH2)(η6-p-cymene)(PRPh2)]2+ (where PRPh2 has R = [−(CH2)5PPh2–Fe(C5H5)(CO)2]+). One interpretation of the combined DNA-interaction and kinetic data is that the mono(aqua) complex may interact with dsDNA through nucleobase coordination. Heterodinuclear 10 reacts with glutathione (GSH) to form stable mono- and bis(thiolate) adducts, 10-SG and 10-SG2, with no evidence of metal ion reduction (k1 = 1.07 ± 0.17 × 10−1 min−1 and k2 = 6.04 ± 0.59 × 10−3 min−1 at 37 °C). This work highlights the synergistic effect of the Fe2+/Ru2+ centres on both the cytotoxicity and biomolecular interactions of the present heterodinuclear complexes.

Multistep synthesis, reactivity and X-ray structure of the anisole-terminated iron(II) polyhalogenoclathrochelates and their monoribbed-functionalized macrobicyclic derivatives

Multistep synthetic pathway towards a series of the anisoleboron-capped ribbed-functionalized iron(II) cage complexes was developed. Their hexachloroclathrochelate precursor was obtained by the template condensation of three dichloroglyoximate chelating ligand synthons with two molecules of 4-methoxyphenylboronic acid as a Lewis-acidic cross-linking agent on the iron(II) ion as a matrix. It easily underwent a stepwise nucleophilic substitution with S2- and O2-dinucleophilic aliphatic (ethanedithiolate) or aromatic (pyrocatecholate) agents, forming the stable X2 (X = S or O)-six-membered ribbed substituent(s) at a quasiaromatic cage framework. Performing these reactions under the different reaction conditions (i.e., at various hexachloroclathrochelate-to-nucleophile molar ratios, a wide range of temperatures and a series of the solvents) allowed to control a predominant formation of its mono-, di- or triribbed-substituted macrobicyclic derivatives. Thus obtained iron(II) di- and tetrachloroclathrochelates can undergo their post-synthetic transformations with active nucleophilic agents. The latter complexes underwent a further nucleophilic substitution with the anionic derivative of n-butanthiol, thus giving the hexasulfide macrobicyclic compound with two functionalizing n-alkyl substituents in one of its three chelate α-dioximate fragments and two apical biorelevant anisole substituents. The obtained iron(II) clathrochelates, possessing a low-spin electronic d6 configuration, were characterized using elemental analysis, MALDI-TOF mass spectrometry, UV–Vis, 1H and 13C{1H} NMR spectroscopies, and by the single-crystal X-ray diffraction experiments for the hexachloroclathrochelate precursor, its dichlorotetrasulfide macrobicyclic derivative and the monoribbed-functionalized hexasulfide cage complex. In all their molecules, the encapsulated iron(II) ion is situated in the centre of its FeN6-coordination polyhedron, the geometry of which is intermediate between a trigonal prism and a trigonal antiprism with the distortion angles φ from 21.4 to 23.4°. Halogen bonding between the polyhalogenoclathrochelate molecules in their crystals is observed.Graphical abstract

Property‐Driven Development of Passively Permeable Macrocyclic Scaffolds Using Heterocycles**

AbstractPassive membrane permeability is a fundamental challenge in the development of bioactive macrocycles. To achieve this objective, chemists have resorted to various strategies, the most common of which is deployment of N‐methylated amino acids and/or D‐amino acids. Here we investigate the effect of heterocyclic grafts on the passive membrane permeability of macrocycles and report the structural consequences of iterative amino acid replacement by azole rings. Through stepwise substitution of amino acid residues for heterocycles, we show that lipophilicity and PAMPA permeability of a macrocycle can be vastly improved. Overall, changes in permeability do not scale linearly as more heterocycles are incorporated, underscoring the subtleties of conformation‐property relationships in this class of molecule. NMR analysis and molecular dynamics simulations provide insights into the structural consequences of the added heterocycles and these frameworks can now be applied as macrocyclic scaffolds for drug discovery.

Property-Driven Development of Passively Permeable Macrocyclic Scaffolds Using Heterocycles.

Passive membrane permeability is a fundamental challenge in the development of bioactive macrocycles. To achieve this objective, chemists have resorted to various strategies, the most common of which is deployment of N-methylated amino acids and/or D-amino acids. Here we investigate the effect of heterocyclic grafts on the passive membrane permeability of macrocycles and report the structural consequences of iterative amino acid replacement by azole rings. Through stepwise substitution of amino acid residues for heterocycles, we show that lipophilicity and PAMPA permeability of a macrocycle can be vastly improved. Overall, changes in permeability do not scale linearly as more heterocycles are incorporated, underscoring the subtleties of conformation-property relationships in this class of molecule. NMR analysis and molecular dynamics simulations provide insights into the structural consequences of the added heterocycles and these frameworks can now be applied as macrocyclic scaffolds for drug discovery.

Monoribbed‐Functionalized Macrobicyclic Iron(II) Complexes Decorated with Terminal Reactive and Vector Groups: Synthetic Strategy, Chemical Transformations and Structural Characterization

Comprehensive SummaryGeneral and straightforward synthetic strategy towards the iron(II) clathrochelates with functionalizing substituents in their apical capping and one of the three chelate ribbed fragments was developed. Their hexachloroclathrochelate precursors were prepared by the direct template condensation of dichloroglyoxime with a suitable boronic acid on the Fe2+ ion as a matrix and underwent a stepwise nucleophilic substitution with S2‐, N2‐ or O2‐bis‐nucleophiles, forming the alicyclic or aromatic N2‐, S2‐ or O2‐six‐membered fragments. Depending on the reaction conditions and precursor‐to‐dinucleophile molar ratios, iron(II) clathrochelates with one (S, O and N), two (S, O and N) or three (S and O) X2‐six‐membered ribbed substituent(s) were obtained. Their reactivity substantially decreases in a row: Cl6‐Cage &gt; Cl4X2‐Cage (where X = S, O or, especially, N) &gt; Cl2X4‐Cage (where X = S or O). The reactive monoribbed‐functionalized clathrochelates underwent further chemical transformations giving the target macrobicyclic complexes with terminal vector groups. As follows from the single crystal XRD data, their FeN6‐coordination polyhedra possess the geometry intermediate between a trigonal prism and a trigonal antiprism (φ = 21.3°—25.20°). Fe—N distances vary from 1.887(6) to 1.933(8) Å. Their 3D‐molecules, the hydrophobic–hydrophilic balance in which can be tuned using a ribbed functionalization, form in the crystals the intermolecular specific halogen bonds and/or hydrophobic interactions.

An Orthogonal Synthetic Approach to Nonsymmetrical Bisazolyl 2,4,6-Trisubstituted Pyridines.

A three-step synthetic route giving access to nonsymmetrical bisazolyl 2,4,6-trisubstituted pyridines with different substituents on the pyrazole, indazole, and pyridine heterocycles is described. From the readily available 4-bromo-2,6-difluoropyridine, both fluorine atoms allow for easy selective stepwise substitution, and the bromine atom provides easy access to additional functionalities through both Suzuki and Sonogashira Pd(0) cross-coupling reactions. These synthons represent optimal structures as building blocks in complexation and metalloorganic structures for the tuning of their chelating and photophysical properties.

Unconventional mechanism and selectivity of the Pd-catalyzed C\u2013H bond lactonization in aromatic carboxylic acid

The search for more effective and highly selective C–H bond oxidation of accessible hydrocarbons and biomolecules is a greatly attractive research mission. The elucidating of mechanism and controlling factors will, undoubtedly, help to broaden scope of these synthetic protocols, and enable discovery of more efficient, environmentally benign, and highly practical new C–H oxidation reactions. Here, we reveal the stepwise intramolecular SN2 nucleophilic substitution mechanism with the rate-limiting C–O bond formation step for the Pd(II)-catalyzed C(sp3)–H lactonization in aromatic 2,6-dimethylbenzoic acid. We show that for this reaction, the direct C–O reductive elimination from both Pd(II) and Pd(IV) (oxidized by O2 oxidant) intermediates is unfavorable. Critical factors controlling the outcome of this reaction are the presence of the η3-(π-benzylic)–Pd and K+–O(carboxylic) interactions. The controlling factors of the benzylic vs ortho site-selectivity of this reaction are the: (a) difference in the strains of the generated lactone rings; (b) difference in the strengths of the η3-(π-benzylic)–Pd and η2-(π-phenyl)–Pd interactions, and (c) more pronounced electrostatic interaction between the nucleophilic oxygen and K+ cation in the ortho-C–H activation transition state. The presented data indicate the utmost importance of base, substrate, and ligand in the selective C(sp3)–H bond lactonization in the presence of C(sp2)–H.

Regioselective Stepwise Bromination of [14]Triphyrins(2.1.1) and Their Effects on Structural, Spectral, and Redox Properties.

Regioselective stepwise bromination of meso-tetraaryl [14]triphyrins(2.1.1) was explored to investigate the effect of bromine substitution at the β-pyrrole carbons of triphyrin(2.1.1) on the structural, spectral, photophysical, and redox properties. A series of β-monobromo to β-hexabromo triphyrins(2.1.1) 2-7 were synthesized by treating triphyrin(2.1.1) 1 with appropriate equivalents of N-bromosuccinimide at ambient temperature in decent yields. The regiochemistry of bromines in β-brominated triphyrins(2.1.1) 3-5 and 7 was confirmed by X-ray crystallography, and the analysis revealed the effect of bromination of triphyrin(2.1.1) on the structural framework was significant in the case of hexabromotriphyrin(2.1.1) 7 compared to other macrocycles. Absorption spectroscopy showed that stepwise substitution of bromines at β-pyrrole carbons of triphyrin(2.1.1) resulting in bathochromic shifts of absorption bands relative to triphyrin(2.1.1) 1 and hexabromotriphyrin(2.1.1) 7 exhibited absorption bands at longer wavelengths. The redox studies revealed that compounds 2-7 were easier to reduce than triphyrin(2.1.1) 1, and the first reduction potential wave shifted anodically with an increase in the number of bromine substituents at β-pyrrole carbons of triphyrin(2.1.1) 1 from one to six. These structural, spectral, and electrochemical properties were also predicted by density functional theory calculations, and the analysis was consistent with the experimental observations.

Synthesis of Multifunctional Charge-Transfer Agents: Toward Single-Walled Carbon Nanotubes with Defined Covalent Functionality and Preserved π System

The attachment of well-defined charge transfer agents to the surface of nanomaterials is an efficient strategy to control their charge density and also to tune their optical, electrical, and physicochemical properties. Particularly interesting are charge transfer agents that either donate or withdraw electrons depending on the arrangements of their building units and that promise a non-destructive attachment to delicate nanomaterials like sp$^2$ compounds. In this work, we rationally synthesize molecular moieties with versatile functionalities. A reactive anchor group allows to attach them to carbon nanotubes as defined charge transfer agents while preserving the tube $\pi$-conjugation. The charge transfer agents were synthesized through the stepwise nucleophilic substitution of either one (monosubstituted series) or two chlorine (disubstituted series) atoms of cyanuric chloride by aniline derivatives containing one, two or three methoxy groups in the para and meta positions. Variation in the number and position of methoxy as an electron transferring group help us to manipulate the electronic and optical properties of the molecular probes and their charge transfer to the SWNTs systematically. The correlation between the optical properties of these molecular probes and their functionality was investigated by experiments and quantum chemical calculations. While the optoelectronic properties of the conjugated charge transfer agents were dominated by the aniline segments, the triazine warrants the ability to nondestructively attach to the surface of SWNTs. This study is one step ahead towards the production of SWNTs with desired optical and electrical properties by covalent $\pi$-preserving functionalization.

Stepwise Li Substitution Induced Structure Evolution and Improved Nonlinear Optical Performance for Diamond-like Sulfides.

One of the key scientific issues for exploration of novel infrared nonlinear optical (NLO) crystals is to obtain ones with good hybrid NLO behaviors. Herein, we report four diamond-like Ag-based sulfides via stepwise Li substitution of Ag in Ag2ZnSnS4, including Ag2ZnSnS4 (1), (Li1.22Ag0.78)ZnSnS4 (2), (Li1.58Ag0.42)ZnSnS4 (3), and Li2ZnSnS4 (4). With the increase of Li content, the sulfide's noncentrosymmetric crystal structure changes from tetragonal I42m for 1, to orthorhombic Pmn21 for 2 and 3, and to monoclinic Pn for 4. Accordingly, their NLO responses are improved along with the increase of Li content, viz. from non-NLO-active for 1, to non-phase-matchable for 2 and 3, and to phase-matchable for 4. Their optical band gaps also increase regularly. The relationship between their chemical compositions, crystal structures, and NLO activities is investigated by means of chemical structural analysis and theoretical calculation. This work offers a new systematic case for designing promising NLO-active compounds via rarely adopted cation's stepwise partial substitution and understanding the chemical composition-structure-NLO property relationship.