Pyrrole Positions Research Articles

Unraveling the Remarkable Influence of Substituents on the Emission Variation and Circularly Polarized Luminescence of Dinuclear Aluminum Triple-Stranded Helicates.

This study explored the development of functional dyes using aluminum, focusing on aluminum-based dinuclear triple-stranded helicates, and examined the effects of substituent variations on their structural and optical properties. Key findings revealed that the modification of methyl groups to the pyrrole positions significantly extended the conjugation system, resulting in a red shift in the absorption and emission spectra. Conversely, the modification of methyl groups at the methine positions due to steric hindrances increased the torsion angle of the ligands, leading to a blue shift in the absorption and emission spectra. A common feature across all complexes was that in the excited state, one of the three ligands underwent significant structural relaxation. This led to a pronounced Stokes shift and minimal spectra overlap with high photoluminescence behaviors. Moreover, our research extended to the optical resolution of the newly synthesized complexes by analyzing the chiroptical properties of the resulting enantiomers, including their circular dichroism and circularly polarized luminescence. These insights offer valuable contributions to the design and application of novel aluminum-based functional dyes, potentially influencing a range of fields, from materials science to optoelectronics.

Enantioselective synthesis of α-(3-pyrrolyl)methanamines with an aza-tetrasubstituted center under metal-free conditions.

Construction of a chiral methanamine unit at the C3 position of pyrrole is highly desirable; nevertheless, it remains challenging due to its intrinsic electronic properties. Herein, we present an operationally straightforward and direct asymmetric approach for accessing α-(3-pyrrolyl)methanamines under benign organocatalytic conditions for the first time. The one-pot transformation proceeds smoothly through an amine-catalyzed direct Mannich reaction of succinaldehyde with various endo-cyclic imines, followed by a Paal-Knorr cyclization with a primary amine. Several N-H/alkyl/Ar α-(3-pyrrolyl)methanamines with an aza-tetrasubstituted center have been synthesized with good yields and excellent enantioselectivity.

Synthesis of four regioisomeric Ni(ii) azacorroles via oxidative ring-expansion of prefunctionalised norcorroles

We explored the synthesis and properties of four regioisomeric Ni(ii) azacorroles. The results revealed that the substituent at different pyrrole positions exerted different effects on the electronic structures.

β-Functionalized palladium(II) porphyrins: Facile synthesis, structural, spectral, and electrochemical redox properties

Two [Formula: see text]-substituted Pd(II) porphyrins, (PdTPP(NO[Formula: see text]Ph2 and PdTPP(Ph)[Formula: see text], were synthesized and characterized by various spectroscopic techniques, and their spectral and electrochemical redox properties were investigated with respect to PdTPP. The single-crystal X-ray structure of PdTPP(NO[Formula: see text]-Ph2 revealed saddle-shape conformation of the macrocyclic core of porphyrin. DFT studies revealed nonplanar saddle shape conformation of PdTPP(Ph)4 with an average deviation of [Formula: see text]-pyrrole carbon atoms from the porphyrin mean plane ([Formula: see text]C[Formula: see text] = ± 0.751 Å) and also 24 core atoms ([Formula: see text]24 = ± 0.368 Å) as compared to PdTPP(NO[Formula: see text]Ph2 ([Formula: see text]C[Formula: see text] = 0.649 Å and [Formula: see text]24 = ± 0.317 Å) due to more [Formula: see text]-pyrrole substitution. Both PdTPP(NO[Formula: see text]Ph2 and PdTPP(Ph)4 exhibited 13-19 nm and 49-59 nm red-shift in the Soret and Q[Formula: see text] bands as compared to PdTPP, respectively. PdTPP(NO[Formula: see text]Ph2 exhibited a very high dipole moment (7.32 D) as compared to PdTPP(Ph)4 (0.239 D) due to the “push-pull” effect of electron donor (phenyl) and acceptor (-NO[Formula: see text] groups at the [Formula: see text]-pyrrole positions of the macrocycle. The redox potentials of PdTPP(NO[Formula: see text]Ph2 anodically shifted ([Formula: see text]E = 0.2-0.4V) as compared to PdTPP and PdTPP(Ph)4 due to the presence of [Formula: see text]-phenyl groups and the strong electron-withdrawing effect of the nitro group. Hence the HOMO-LUMO energy gap of PdTPP(NO[Formula: see text]Ph2 decreased by 0.20 V and 0.28 V as compared to PdTPP(Ph)4 and PdTPP, respectively.

Co(II)-porphyrin complexes with nitrogen monoxide and imidazole: synthesis, optimized structures, electrochemical behavior and photochemical stability

UV-vis and 1H-NMR spectroscopy were applied to study axial coordination of imidazole (L1) and nitrogen monoxide (L2) with CoII-porphyrins (CoIIP) containing halogen substituents in the pyrrole and meso-phenyl positions of the macrocycle. The number and positions of bromine and chlorine atoms cause considerable deformation of the tetrapyrrole macrocycle. Cyclic voltammetry was used to determine the oxidation potentials of CoII/CoIII (Е1 ох) in the compounds. Both mono-axial complexes (CoII(L)) and diaxial complexes (CoIIIP(L)2) or CoIIP-π cation radicals could be the products of CoIIP interaction with L1 and L2, depending on the porphyrinate structure. The interconnection between halogen substitution in the porphyrin macrocycle and its ability to reversibly bind NO was established. The photochemical activity of the synthesized complexes in the presence of active oxygen forming (tert-butylperoxide) was investigated. The results extend our understanding of the valence state of cobalt cations in porphyrin molecules depending on the macrocycle structure and surrounding conditions (solvent, temperature, organic and inorganic impurities), and demonstrate the possibility of reversible binding of both the NO molecules and various imidazole-containing biomolecules and drug compounds based on them.

Tuning the Properties of Azadipyrromethene-Based Near-Infrared Dyes Using Intramolecular BO Chelation and Peripheral Substitutions.

Tetraphenylazadipyrromethenes (ADPs) are attractive near-infrared (NIR) dyes because of their simple synthesis and exceptional optical and electronic properties. The typical BF2 and less explored intramolecular BO coordination planarize the molecule, making them promising π-conjugated materials for organic electronic applications. However, their use has been mostly limited to vacuum-deposited devices. To improve the properties, we synthesized and characterized a series of ADP complexes and used density functional theory calculations to further explain the properties. Hexyloxy solubilizing groups increase the complexes' solubility in organic solvents and enable film formation from solution. Phenylethynyls at the pyrrolic positions extend π conjugation, red-shift absorption and emission peaks, and increase the ionization potential (IP) and electron affinity. When the properties of complexes with hexyloxy and phenyethynyl substitutions are compared, the BO complex is more planar and has a smaller IP than the corresponding BF2 complex because of increased electron density on the proximal phenyls. The BO complex has an unusual combination of properties: a solution λmax of 781 nm, emission at 805 nm, a small Stokes shift, and a quantum yield of 6%. It forms transparent films with a low optical gap of 1.22 eV. This new complex is a promising candidate for transparent solar cells and NIR photodetectors.

Effect of solvent on the electronic absorption spectral properties of mixed β-octasubstituted free base tetraphenylporphyrins

A near planar macrocycle containing 2,3,12,13-tetraphenylethynyl-5,10,15,20-tetrakis-(4[Formula: see text]-[Formula: see text]-butylphenyl)porphyrin, H2T(4[Formula: see text]-[Formula: see text]-Bu Ph)P(PE)4 and a series of antipodally mixed substituted nonplanar porphyrins, 2,3,5,10,12,13,15,20-octaphenyl-7,8,17,18-tetra(2[Formula: see text]-thienyl/phenylethynyl, PE)porphyrin, H2OPP(2[Formula: see text]-Th/PE)4 and 2,3,12,13-tetramethyl-7,8,17,18-tetra(2[Formula: see text]-thienyl/PE)-5,10,15,20-tetraphenylporphyrin, H2TPP(CH[Formula: see text](2[Formula: see text]-Th/PE)4were examined by electronic absorption spectroscopy in twenty different solvents. The presence of push-pull substituents at the antipodal [Formula: see text]-pyrrole positions of the nonplanar macrocycle induces varying degrees of orthogonal dipole moments to the porphyrin ring. The influence of different solvents on the degree of nonplanarity and electronic nature of the macrocycle on their electronic absorption spectral properties were examined. Generally, free base porphyrins showed dramatic solvent dependent absorption spectral band shifts and follow the order: H2OPP(PE)4 > H2OPP(2[Formula: see text]-Th)[Formula: see text] H2TPP(CH[Formula: see text](2[Formula: see text]-Th)4 >[Formula: see text]H2TPP(CH[Formula: see text](PE)4 > H2T(4[Formula: see text]-[Formula: see text]Bu Ph)P(PE)4. Absorption spectral data in different solvents was analyzed using selected solvatochromic parameters, ([Formula: see text] – 1)/(2[Formula: see text] + 1), [Formula: see text] (30),[Formula: see text], and [Formula: see text]*. The enhanced red-shift of the absorption bands of the mixed substituted porphyrins in polar solvents was influenced by solvent-core (porphyrin) interaction and is reflected from the 1H NMR chemical shift of the core imino-hydrogens in polar solvents relative that observed in less polar solvents. The magnitude of the difference in chemical shift ([Formula: see text], ppm) of imino-hydrogens in DMSO-d6 relative to that in CDCl3 follow the order: H2TPP(CH[Formula: see text](2[Formula: see text]-Th)4 (1.37 ppm) > H2OPP(PE)4 (1.17 ppm) > H2TPP(CH[Formula: see text](PE)4 (0.57 ppm). The large red-shift in B and Q bands in polar solvents relative to apolar (or less polar) solvents has been possible due to the combined effect of the electronic nature of the macrocycle, its nonplanarity, and solvent-porphyrin core interactions.

Thermochromic and highly tunable color emitting bis-tolane based liquid crystal materials for temperature sensing devices

The luminescent compounds based on the D-π-A system consisting of substituted pyrrole as acceptor, π conjugated bis-tolane and -OMe, -N(CH3)2, -N(Ph)2 at termini acting as donors have been synthesized. On heating, all the compounds exhibited distinct mesomorphic behavior depending upon donating groups and substituents at the acceptor unit. These luminescent liquid crystals exhibited emission from blue, green to reddish orange with high quantum efficiency in solid as well in solutions state. We discovered the rarely reported three membered ring interactions between the Br at alpha position of pyrrole and acetylene bond and their impact on luminescence efficiency via single crystal structure of 2Br–CN–N(CH3)2 and 2Br–CN–N(Ph)2. Furthermore, the thermochromic behavior of these LLCs compounds has been explored, especially CN–N(Ph)2, its reddish orange emission changed to blue at 240 °C–250 °C in pure state, while in dimethyl silicone polymer (PDMS) film, it switched to blue at 200 °C and completely vanished at 240 °C. These simple and highly emissive compounds display outstanding thermochromic properties above 200 °C, thus will be potentiality valuable for high temperature sensing devices.

Large Non-planar Conjugated Molecule with Strong Intermolecular Interactions Achieved with Homoleptic Zn(II) Complex of Di(5-quinolylethynyl)-tetraphenylazadipyrromethene.

Zinc(II) complexes of tetraphenylazadipyrromethenes are potential non-planar n-type conjugated materials. To tune the properties, we installed 5-quinolylethynyl groups at the pyrrolic positions. Compared to the complex with 1-napthylethynyl, we found evidence for stronger intermolecular interactions in the new complex, including much higher overlap integrals in crystals. X-ray analysis revealed unconventional C–H···N hydrogen bonding between two quinolyls of neighboring molecules, pointing to a new strategy for the development of non-planar molecular semiconductors with stronger intermolecular interactions.

Total Synthesis of Phorbazole B.

Phorbazoles are polychlorinated heterocyclic secondary metabolites isolated from a marine sponge and several of these natural products have shown inhibitory activity against cancer cells. In this work, a synthesis of the trichlorinated phorbazole B using late stage electrophilic chlorination was developed. The synthesis relied on the use of an oxazole precursor, which was protected with an iodine in the reactive 4-position, followed by complete chlorination of all pyrrole positions. Attempts to prepare phorbazole A and C, which contain a 3,4-dichlorinated pyrrole, were unsuccessful as the desired chlorination pattern on the pyrrole could not be obtained. The identities of the dichlorinated intermediates and products were determined using NMR techniques including NOESY/ROESY, 1,1-ADEQUATE and high-resolution CLIP-HSQMBC.

Side‐chain engineering of perylene diimide dimers: Impact on morphology and photovoltaic performance

AbstractMorphology evolution of conjugated organic molecular materials in the solid state has important implications for optoelectronic applications. Two aspects that have a large impact on materials self‐assembly in the film are the nature of the side‐chains and the processing conditions. Films of N‐annulated perylene diimide (PDI) dimer derivatives with different side‐chains at the pyrrolic and imide N‐positions are herein studied after solution processing using the solvent additives 1,8‐diiodooctane (DIO) or diphenyl ether (DPE). Branched or cyclohexyl side‐chains are investigated at the imide position (compounds 1 vs. 2) while linear, cyclic or branched alkyl side‐chains are investigated at the pyrrolic position (compounds 1 vs. 3 vs. 4). Film morphology of the four materials were examined using polarized light, fluorescence, and atomic force microscopy (POM, FM, and AFM, respectively). Organic photovoltaic (OPV) devices using the donor polymer PTB7‐Th with each PDI dimer as a non‐fullerene acceptor (NFA) were fabricated and tested to correlate morphology to electronic performances. Cyclohexyl side‐chains at the imide position reduced PDI dimer (2) solubility, gave flower like crystals in the film, and overall poor OPV performance regardless of processing. Cyclic alkyl side‐chains at the pyrrolic position impeded PDI dimer (3) crystallization and lead to moderate OPV performance. A combination of branched and linear side‐chains on the PDI dimer (compounds 1 and 4) provided sufficient solubility in non‐halogenated solvents and best OPV performance without the use of processing additives. For 1 with linear side‐chains at the pyrrolic position, processing with additives lead to moderate crystallization and improved OPV performance. For 4 with branched‐side chains, processing with additives lead to major crystallization and poor OPV performance. Side‐chain engineering is critical for controlling the self‐assembly of N‐annulated PDI dimers and it was shown that the choice and volume of processing additive must be evaluated systematically for maximizing electronic performance.

New spiro-borane and spiro-borate derived from dipyrromethane and their H/D exchange properties

The reaction between diethyldipyrromethane Et2C(C4H4N)2 and BH3·THF or the treatment of the lithium salt of dipyrromethane with BF3·OEt2 in THF gave a new four coordinate boron(III) compound 1 having the spiro structure formed by one dianionic and one monoanionic dipyrromethane units. Compound 1 contains one 2H-pyrrole ring and is acidic. Hence, it readily reacts with bases such as n-Bu4NOH, NaH, DMAP or Et3N to give the spiroborate complexes 2 containing two dianionic dipyrromethane moieties. The deprotonation of 1 gives back aromaticity to the pyrrole ring. Compound 1 is rigid, a rather well resolved 1H NMR spectrum was obtained in aromatic solvents compared to CDCl3 and peaks were assigned using 2D NOESY spectrum. Compound 1 showed fast hydrogen-deuterium exchanges at the pyrrolic positions in CDCl3/D2O or CD3CN/D2O mixture catalyzed by HBF4. However, the H/D exchange occurs in step wise fashion as shown by 1H NMR analysis. The structures of compound 1 and 2 were confirmed by spectroscopic and X-ray diffraction methods.

Synthesis, spectral and crystal structures of gem-dibromovinyl boron dipyrrins

A series of BODIPYs (boron-dipyrromethene dyes; 4,4-difluoro-5-aryl-4-bora-3a,4a-diaza-s-indacene) derivatives, bearing an aldehyde group at different pyrrole positions, were transformed into gem-dibromovinyl analogs using the Corey-Fuchs or Lautens olefination method. The gem-dibromovinyl moieties (one or two) are symmetric/asymmetric and attached at α- or β-positions of the pyrrole ring, directly or through the extension of a β-position substituted phenyl spacer ring. The molecular structures of the resultant dyes were assigned using MS, 1H, 13C, 19F NMR, X-ray diffraction and for some compounds 2D HSQC and 11B NMR. The absorption, fluorescence and solvatochromism properties were investigated in different solvents. The highest absorption and emission maxima were obtained for compounds having two gem-dibromovinyl groups attached directly at the α-positions. The best correlation (R-coefficient) of absorption between the solvents and spectral properties of the BODIPYs was obtained using the refractive index of the solvent. The R-coefficient of emission was obtained only for compounds having gem-dibromo vinyl moieties at α-positions. Their solid states clearly reveal distinct patterns of gem-dibromovinyl orientation, torsion angles of the 5-phenyl ring and the indacene plane. Hirshfeld surface analyses were used to visualize various intermolecular interactions.

Design of metalloporphyrins fused to imidazolium rings for binding DNA G-quadruplexes

Synthesis and characterization of nickel(II) meso-tetraarylporphyrins fused to imidazolium rings across [Formula: see text],[Formula: see text]-pyrrolic positions and X-ray structure of the porphyrin where two opposed pyrrole units are fused to an imidazolium ring are presented. The interactions between these mono-, bis-, tris- and tetrakis(imidazolium) porphyrins with human telomeric DNA G-quadruplexes (G4) were investigated using UV-vis absorption spectroscopy, Circular Dichroism (CD) spectroscopy and Fluorescence Resonance Energy Transfer (FRET) melting assay. Possible binding modes between cationic porphyrins and a selected G4 sequence (d[AG3(T2AG[Formula: see text]]), and relative stabilities of porphyrin/G4 complexes are discussed. Excepting porphyrins fused to one imidazolium ring, the other derivatives interact with G4 structures and their stabilization strongly depends on the porphyrin structure (number and localization of the imidazolium rings).

Push–Pull Porphyrins via β‐Pyrrole Functionalization: Evidence of Excited State Events Leading to High‐Potential Charge‐Separated States

A new set of free-base and zinc(II)-metallated, β-pyrrole-functionalized unsymmetrical push-pull porphyrins were designed and synthesized via β-mono- and dibrominated tetraphenylporphyrins using Sonogashira cross-coupling reactions. The ability of donors and acceptors on the push-pull porphyrins to produce high-potential charge separated states was investigated. The porphyrins were functionalized at the opposite β,β'-pyrrole positions of porphyrin ring bearing triphenylamine push groups and naphthalimide pull groups. Systematic studies involving optical absorption, steady-state and time-resolved emission revealed existence of intramolecular type interactions both in the ground and excited states. The push-pull nature of the molecular systems was supported by frontier orbitals generated on optimized structures, wherein delocalization of HOMO over the push group and LUMO over the pull group connecting the porphyrin π-system was witnessed. Electrochemical studies were performed to visualize the effect of push and pull groups on the overall redox potentials of the porphyrins. Spectroelectrochemical studies combined with frontier orbitals helped in characterizing the one-electron oxidized and reduced porphyrins. Finally, by performing transient absorption studies in polar benzonitrile, the ability of push-pull porphyrins to produce charge-separated states upon photoexcitation was confirmed and the measured rates were in the range of 109 s-1 . The lifetime of the final charge separated state was around 5 ns. This study ascertains the importance of push-pull porphyrins in solar energy conversion and diverse optoelectronic applications, for which high-potential charge-separated states are warranted.

Azadipyrromethene-based near-IR dyes with styryl substituents at the pyrrolic positions for organic photovoltaic applications

Azadipyrromethene dyes are attractive building blocks for the development of near-IR dyes, with applications ranging from biosensing, photodynamic therapy and solar energy conversion. In particular, Zn(II) bis(2,8-diphenylethynyl 1,3,7,9 tetraphenylazadipyrromethene) complexes are promising n-type non-fullerene electron acceptors for organic photovoltaics. Here, the triple bond in phenylethynyl pyrrolic substituents is replaced with a double bond. The UV–Vis absorption spectra were not significantly different, indicating that both the double and triple bond similarly extend the conjugation of ADP. Interestingly, the Zn(II) complex with styryl substituents (Zn(WS6)2) showed emission in the near IR, with a λmax of 773 nm. The BF2+ chelate also emitted in the near IR with a λmax of 815 nm, but the emission was very weak. Cyclic voltammetry revealed that double bond compounds were easier to oxidize than un-substituted ADP analogues, and unlike with triple bond, were not easier to reduce. In organic photovoltaics, the Zn(WS6)2 did not perform as well as the Zn(WS3)2 analogue, showing unfavorable film morphology when blended with P3HT and low blend electron mobility of 2 × 10−8 cm2V−1s−1 by SCLC, compared to 1 × 10−7 cm2V−1s−1 in neat film. The hole mobility of Zn(WS6)2 in neat films is 6 × 10−5 cm2V−1s−1, higher than its electron mobility, suggesting its potential as p-type material as well. Further work in finding an appropriate n-type polymer acceptor is required to confirm this hypothesis. Using a triple bond at the pyrrolic positions is therefore better than a double bond for the development of n-type materials based on ADP dyes.

Regioselectively Halogenated Expanded Porphyrinoids as Building Blocks for Constructing Porphyrin-Porphyrinoid Heterodyads with Tunable Energy Transfer.

Expanded porphyrins have been attracting increasing attention owing to their unique optical and electrochemical properties as well as switchable aromaticity. Toward material applications, regioselective functionalization of the expanded porphyrins at their periphery is indeed challenging due to the presence of multiple reactive sites. Herein, a set of regioselective halogenated isomers (L5-Br-A/B/C) of neo-confused isosmaragdyrin (L5) are synthesized by a combination of the halogenation reaction of L5 and sequential macrocycle-to-macrocycle transformation reactions of its halogenated isomers. On this basis, the regioselectively functionalized isosmaragdyrins are utilized as building blocks for constructing multichromophoric porphyrinoids, specifically, heterodyads L5-ZnP-A/B/C, in which a common zinc porphyrin is linked at three different pyrrolic positions of isosmaragdyrins, respectively, by Sonogashira coupling reactions. The highly efficient energy cascade from porphyrin to isosmaragdyrin is elucidated using steady-state/time-resolved spectroscopies and theoretical calculations. Notably, the energy transfer processes from the porphyrin to the isosmaragdyrin moieties as well as the excitation energy transfer rates in L5-ZnP-A/B/C are highly dependent on the linking sites by through-bond and Förster-type resonance energy transfer mechanisms. The site-selective functionalization and subsequent construction of a set of heterodyads of the expanded porphyrinoid would provide opportunities for developing new materials for optoelectronic applications.

Synthesis and crystallographic characterization of a brominated porphyrin with a nitrophenyl substituent and its iron derivative

2,3,7,8,12,13,17,18-Octabromo-5-(2-nitrophenyl)-10,15,20-triphenyl porphyrin (H[Formula: see text]OBP-NO[Formula: see text] and its metallic complexes have been designed and synthesized. Both the free-base porphyrin and its iron(III) complex have been characterized by X-ray crystallography. Structures confirm there are three phenyl groups and one 2-nitrophenyl at meso positions and eight bromine atoms at [Formula: see text]-pyrrole positions. The crowded substituents cause the porphyrin plane to be distorted and become saddle shaped. The complexes were also characterized by NMR and UV-vis spectra. The UV-vis spectrum of the free-base porphyrin shows that substitution by eight bromine atoms at [Formula: see text]-pyrrole positions leads to a red shift of the bands.

Theoretical Investigation of the Formation Mechanism of NH₃ and HCN during Pyrrole Pyrolysis: The Effect of H₂O.

Coal is a major contributor to the global emission of nitrogen oxides (NOx). The NOx formation during coal utilization typically derives from the thermal decomposition of N-containing compounds (e.g., pyrrolic groups). NH3 and HCN are common precursors of NOx from the decomposition of N-containing compounds. The existence of H2O has significant influences on the pyrrole decomposition and NOx formation. In this study, the effects of H2O on pyrrole pyrolysis to form NOx precursors HCN and NH3 are investigated using the density functional theory (DFT) method. The calculation results indicate that the presence of H2O can lead to the formation of both NH3 and HCN during pyrrole pyrolysis, while only HCN is formed in the absence of H2O. The initial interaction between pyrrole and H2O determines the N products. NH3 will be formed when H2O attacks the C2 position of pyrrole with its hydroxyl group. On the contrary, HCN will be generated instead of NH3 when H2O attacks the C3 position of pyrrole with its hydroxyl group. In addition, the DFT calculations clearly indicate that the formation of NH3 will be promoted by H2O, whereas the formation of HCN is inhibited.

Design and synthesis of neolamellarin a derivatives targeting heat shock protein 90

In this study, we designed and synthesized a novel family of neolamellarin A derivatives that showed high inhibitory activity toward heat shock protein 90 (Hsp90), a kinase associated with cell proliferation. The 3,4-bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N position of pyrrole are essential to the Hsp90 inhibitory activity and cytotoxicity of these compounds. Western blot analysis demonstrated that these compounds induced dramatic depletion of the examined client proteins of Hsp90, and accelerated cancer cell apoptosis. Docking simulations suggested that the binding mode of 9p was similar to that of the VER49009, a potent inhibitor of Hsp90. Further molecular dynamics simulation indicated that the hydrophobic interactions as well as the hydrogen bonds contributed to the high affinity of 9p to Hsp90.