Perylene‐based Solution‐processable Conjugated Molecules for Optoelectronic Applications: Synthesis and Comparison of Different Substituents on the Optical,Thermal, and Electrochemical Properties

A series of small organic molecules were synthesized by exploiting the bay and imide positions of the perylene nucleus. The synthesized compounds 1 – 11 were characterized by spectroscopic and elemental analyses. These molecules show yellowish color in solution and are highly soluble in dichloromethane. Compound 7 shows a bandgap of 1.7 eV and a Stokes shift of 27. From these results, we infer that this compound can serve as structural template in the design of organic electronics. Moreover, compound 7 shows higher T_d (370°C) and T_g (132°C) values, which reflect its high thermal stability.     

Remarkable Enhancement of Hole Mobility of Novel DA-D’-AD Small Molecules by Thermal Annealing: Effect of the D’-Bridge Block.

Conjugated small molecules are advanced semiconductor materials with attractive physicochemical and optoelectronic properties enabling the development of next-generation electronic devices. The charge carrier mobility of small molecules strongly influences the efficiency of organic and hybrid electronics based on them. Herein, we report the synthesis of four novel small molecules and their investigation with regard to the impact of molecular structure and thermal treatment of films on charge carriers’ mobility. The benzodithiophene-containing compounds (BDT) were shown to be more promising in terms of tuning the morphology upon thermal treatment. Impressive enhancement of hole mobilities by more than 50 times was found for annealed films based on a compound M4 comprising triisopropylsilyl-functionalized BDT core. The results provide a favorable experience and strategy for the rational design of state-of-the-art organic semiconductor materials (OSMs) and for improving their charge-transport characteristics.     

Identification of a Lead Candidate in the Search for Carbene‐Stabilised Homoaromatics

The effect of carbenes as Lewis donor groups on the homoaromaticity of mono‐ and bicyclic organic molecules is surveyed. The search for viable carbene‐stabilised homoaromatics resulted in a large amount of rejected candidates as well as nine promising candidates that are further analysed for their homoaromaticity by using a number of metrics. Of these, five appeared to show modest homoaromaticity, whereas another compound showed a level of homoaromaticity comparable with the homotropylium cation benchmark compound. Isoelectronic analogues and constitutional isomers of the lead compound were investigated, however, none of these showed comparable homoaromaticity. The implications of these calculations on the design of donor‐stabilised homoaromatics are discussed.     

Heats of immersion of active carbon in organic compounds. 1. Heat effects upon immersion of dry and moist active carbon in organic compounds

Heats of immersion (wetting) in organic liquids are determined experimentally for active carbon samples, dry and wet to various degrees. It is shown that the heat of immersion of dry active carbon is related to the degree of accessibility of the depth of the micropores of the sorbent to the molecules of an organic compound. It is suggested that during immersion of moist active carbon the degree of displacement of water from the micropores by molecules of the wetting liquid is related to a steric factor, the ratio between the critical diameter of the adsorbate molecule and the size of the micropore. A method is proposed for calculating heat effects during wetting of active carbon with liquids to various degrees of wetness. The calculated values were compared with experimental data.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1733–1736, August, 1991.     

The Symbiotic Relationship Between Drug Discovery and Organic Chemistry

All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high-quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity-, biology-, lead-, or fragment-oriented syntheses; and DNA-encoded libraries) are critically surveyed.     

Controlling ultralong room temperature phosphorescence in organic compounds with sulfur oxidation state

Sulfur oxidation state is used to tune organic room temperature phosphorescence (RTP) of symmetric sulfur-bridged carbazole dimers. The sulfide-bridged compound exhibits a factor of 3 enhancement of the phosphorescence efficiency, compared to the sulfoxide and sulfone-bridged analogs, despite sulfone bridges being commonly used in RTP materials. In order to investigate the origin of this enhancement, temperature dependent spectroscopy measurements and theoretical calculations are used. The RTP lifetimes are similar due to similar crystal packing modes. Computational studies reveal that the lone pairs on the sulfur atom have a profound impact on enhancing intersystem crossing rate through orbital mixing and screening, which we hypothesize is the dominant factor responsible for increasing the phosphorescence efficiency. The ability to tune the electronic state without altering crystal packing modes allows the isolation of these effects. This work provides a new perspective on the design principles of organic phosphorescent materials, going beyond the rules established for conjugated ketone/sulfone-based organic molecules.

Sulfur lone pairs in bridged dimers enhance intersystem crossing and phosphorescence through orbital mixing and electrostatic screening.     

Indolo‐Phakellins as β5‐Specific Noncovalent Proteasome Inhibitors

The proteasome represents an invaluable target for the treatment of cancer and autoimmune disorders. The application of proteasome inhibitors, however, remains limited to blood cancers because their reactive headgroups and peptidic scaffolds convey unfavorable pharmacodynamic properties. Thus, the discovery of more drug‐like lead structures is indispensable. In this study, we present the first structure of the proteasome in complex with an indolo‐phakellin that exhibits a unique noncovalent binding mode unparalleled by all hitherto reported inhibitors. The natural product inspired pentacyclic alkaloid binds solely and specificially into the spacious S3 subpocket of the proteasomal β5 substrate binding channel, gaining major stabilization through halogen bonding with the protein backbone. The presented compound provides an ideal scaffold for the structure‐based design of subunit‐specific nonpeptidic proteasome‐blockers.     

The structure-based design of Mdm2/Mdmx-p53 inhibitors gets serious

The p53 protein is the cell's principal bastion of defense against tumor-associated DNA damage. Commonly referred as a "guardian of the genome", p53 is responsible for determining the fate of the cell when the integrity of its genome is damaged. The development of tumors requires breaching this defense line. All known tumor cells either mutate the p53 gene, or in a similar number of cases, use internal cell p53 modulators, Mdm2 and Mdmx proteins, to disable its function. The release of functional p53 from the inhibition by Mdm2 and Mdmx should in principle provide an efficient, nongenotoxic means of cancer therapy. In recent years substantial progress has been made in developing novel p53-activating molecules thanks to several reported crystal structures of Mdm2/x in complex with p53-mimicking peptides and nonpeptidic drug candidates. Understanding the structural attributes of ligand binding holds the key to developing novel, highly effective, and selective drug candidates. Two low-molecular-weight compounds have just recently progressed into early clinical studies.     

Synthesis and binding studies of Alzheimer ligands on solid support

Aminopyrazole derivatives constitute the first class of nonpeptidic rationally designed beta-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure form. Hexa- and octapeptide pendants with internal di- and tetrapeptide bridges are now amenable in high yields to combinatorial synthesis of compound libraries for high-throughput screening purposes. Solid-phase peptide synthesis (SPPS) on an acid-resistant PAM allows us, after PMB deprotection, to subject the free aminopyrazole binding sites in an immobilized state to on-bead assays with fluorescence-labeled peptides. From the fluorescence emission intensity decrease, individual binding constants can be calculated via reference curves by simple application of the law of mass action. Gratifyingly, host/guest complexation can be monitored quantitatively even for those ligands, which are almost insoluble in water.     

The effect of organic sorbates on water associated with environmentally important sorbents: estimating and the LFER analysis

The effect of organic sorbates on the water associated with naturally occurring sorbents is of significant interest since it probes the hydration of a sorbate-specific microenvironment and its role in a compound partitioning between various environmental compartments. This effect was described in a thermodynamically strict way by converting the sorption isotherms of organic vapors on variously hydrated sorbents into the derivatives relating the change in the amount of water associated with a sorbent to the change in the amount of an organic sorbate. Further, these derivatives were analyzed by means of the Linear Free Energy Relationship (LFER). The analysis included the sorption data for various organic vapors on such environmentally important sorbents as quartz, metal oxides, calcite, clay minerals and humic acid. From the LFER analysis it followed that (i) organic sorbate polarizability contributions from n- and π-electrons resulted in driving water into the sorbent phase; (ii) the increasing volume of the organic compounds involved expelling water molecules; (iii) the increasing hydrogen-bond acidity and basicity of organic sorbates resulted in expelling water from inorganic surfaces but in enhancing hydration of the humic phase. In contrast to inorganic surfaces, when sorbed on strongly hydrated humic acid, the majority of organic sorbates containing oxygen, nitrogen or sulfur atoms drive water into the sorbent phase. Several molecules of water may need to be cosorbed by a humic sorbent for each sorbed molecule of an organic compound thus supporting the possibility of the concomitant participation of a number of water molecules in organic sorbate–humic matter interactions.