An Inbuilt Electronic Pawl Gates Orbital Information Processing and Controls the Rotation of a Double Ratchet Rotary Motor.

A direct external input energy source (e.g., light, chemical reaction, redox potential, etc.) is compulsory to supply energy to rotary motors for accomplishing rotation around the axis. The stator leads the direction of rotation, and a sustainable rotation requires two mutual input energy supplies (e.g., light and heat, light and pH or metal ion, etc.); however, there are some exceptions (e.g., covalent single bond rotors and/or motors). On the contrary, our experiment suggested that double ratchet rotary motors (DRMs) can harvest power from available thermal noise, kT, for sustainable rotation around the axis. Under a scanning tunneling microscope, we have imaged live thermal noise movement as a dynamic orbital density and resolved the density diagram up to the second derivative. A second input energy can synchronize multiple rotors to afford a measurable output. Therefore, we hypothesized that rotation control in a DRM must be evolved from an orbital-level information transport channel between the two coupled rotors but was not limited to the second input energy. A DRM comprises a Brownian rotor and a power stroke rotor coupled to a -C≡C- stator, where the transport of information through coupled orbitals between the two rotors is termed the vibrational information flow chain (VIFC). We test this hypothesis by studying the DRM's density functional theory calculation and variable-temperature 1H nuclear magnetic resonance. Additionally, we introduced inbuilt pawl-like functional moieties into a DRM to create different electronic environments by changing proton intercalation interactions, which gated information processing through the VIFC. The results show the VIFC can critically impact the motor's noise harvesting, resulting in variable rotational motions in DRMs.

Design and Synthesis of RhodIndolizine Dyes with Improved Stability and Shortwave Infrared Emission up to 1250 nm.

The design of shortwave infrared (SWIR) emissive small molecules with good stability in water remains an important challenge for fluorescence biological imaging applications. A series of four SWIR emissive rhodindolizine (RI) dyes were rationally designed and synthesized to probe the effects of nonconjugated substituents, conjugated donor groups, and nanoencapsulation in a water-soluble polymer on the stability and optical properties of the dyes. Steric protecting groups were added at the site of a significant LUMO presence to probe the effects on stability. Indolizine donor groups with added dimethylaniline groups were added to reduce the electrophilicity of the dyes toward nucleophiles such as water. All of the dyes were found to absorb (920-1096 nm peak values) and emit (1082-1256 nm peak values) within the SWIR region. Among xanthene-based emissive dyes, emission values >1200 nm are exceptional with 1256 nm peak emission being a longer emission than the recent record setting VIX-4 xanthene-based dye. Half-lives were improved from ∼5 to >24 h through the incorporation of either steric-based core protection groups or donors with increased donation strength. Importantly, the nanoencapsulation of the dyes in a water-soluble surfactant (Triton-X) allows for the use of these dyes in biological imaging applications.

SWIR emissive RosIndolizine dyes with nanoencapsulation in water soluble dendrimers.

Shortwave infrared (SWIR) emission has great potential for deep-tissue in vivo biological imaging with high resolution. In this article, the synthesis and characterization of two new xanthene-based RosIndolizine dyes coded PhRosIndz and tolRosIndz is presented. The dyes are characterized via femtosecond transient absorption spectroscopy as well as steady-state absorption and emission spectroscopies. The emission of these dyes is shown in the SWIR region with peak emission at 1097 nm. TolRosIndz was encapsulated with an amphiphilic linear dendritic block co-polymer (LDBC) coded 10-PhPCL-G3 with high uptake yield. Further, cellular toxicity was examined in vitro using HEK (human embryonic kidney) cells where a >90% cell viability was observed at practical concentrations of the encapsulated dye which indicates low toxicity and reasonable biocompatibility.

Cu-Catalyzed Direct Diversification of 2-(2-Bromophenyl)quinazolin-4(3H)-ones through Orthogonal Reactivity Modulation.

A modular strategy to obtain three different products from a single substrate was developed. The present methodology unveils new step-economical and cost-efficient routes to access diverse fused quinazolinoquinazolinone derivatives which are not prevalent in literature. Owing to the importance of quinazolinones in therapeutics, quick access to the arena of these scaffolds could be a valuable addition to the scientific domain of heterocyclic chemistry.

Efficient Detection of Early Events of α-Synuclein Aggregation Using a Cysteine Specific Hybrid Scaffold.

In this study, we have designed and synthesized a new hybrid ligand (SCG) that can selectively detect cysteine in the free and protein-bound states within minutes at the subnanomolar level. Photoinduced electron transfer was responsible for the visible color change as well as a large increase in steady state fluorescence. This detection was validated by using multiple model protein systems with differing cysteine environments and spatial arrangements. SCG was able to monitor the early events of the folding/aggregation kinetics of α-synuclein, a protein involved in the pathology of Parkinson's disease. The early events consisted of conformational fluctuations between different forms of the protein and oligomer formation. SCG was found to be effective in detecting early isomers of α-syn in vitro and in live cell environments.

Detection of Lysosome by a Fluorescent Heterocycle: Development of Fused Pyrido-Imidazo-Indole Framework via Cu-Catalyzed Tandem N-Arylation.

Fluorescent active small molecules for organelle-specific bioimaging are in great demand. We synthesized 20 different pyrido-imidazo-indole fused heterocycles (6-5-5-6 ring) via copper catalyzed tandem N-arylation reaction in moderate to good yields. Due to decent fluorescent property, lysosome-directing moieties were attached on two of these heterocycles. Delightfully, those molecules tracked lysosome with bright blue fluorescence and colocalized with a known lysosome marker (Lysotracker Red) in human/murine cells. Therefore, it may be considered as a rapid (10 min) lysosome staining probe.

Expedient synthesis of a phenanthro-imidazo-pyridine fused heteropolynuclear framework via CDC coupling: a new class of luminophores.

We herein report the design and synthesis of a group of fused phenanthro-imidazo[1,2-a]pyridine derivatives as a new class of luminescent materials through a Pd(ii) catalyzed intramolecular CDC (cross dehydrogenative coupling) reaction. This method thus unlocked a convenient & expedient way for the synthesis of a new molecular framework containing π-extended fused heteropolycycles. The heteropolycycles showed very good fluorescence properties both in solid and solution phases which were further utilized in live cell imaging. These kinds of molecules have potential to be used as therapeutic probes and also their solid state luminescence properties can be further utilized for making optoelectronic devices.

Neo-tanshinlactone D-ring modified novel analogues induce apoptosis in human breast cancer cell via DNA damage.

Neo-tanshinlactone (NTL) a natural product is known for its specificity and selectivity towards the breast cancer cells. By NTL D-ring modification approach, 13 new analogues were synthesized (1A-1M). Among them 1J showed the best anticancer activity in MCF-7 (ER+, PR+/-, HER2-), SKBR3 (ER-, PR-, HER2+) and MDA-MB-231 (ER-, PR-, HER2-) cells lines with IC50 value 11.98nM, 23.71nM, and 62.91nM respectively. 1J showed minor grove binding interaction with DNA at AT-rich region and induced DNA double strand breaks (DDSBs). This had triggered several key molecular events involving, activation of ATM, Chk2 and p53, reduction in mitochondrial potential (Δψm) leading to caspase-3 and PARP cleavage mediated apoptosis. These results along with other biochemical studies strongly suggest that novel NTL analogue 1J caused DNA cleavage mediated apoptosis in the breast cancer cells and this may serve as potential lead for future breast cancer treatment.

Regioselective Synthesis of Quinazolinone-/Phenanthridine-Fused Heteropolycycles by Pd-Catalyzed Direct Intramolecular Aerobic Oxidative C-H Amination from Aromatic Strained Amides.

A new route for the expedient synthesis of specific regioisomer of quinazolinone- and phenanthridine-fused heterocycles through a palladium-catalyzed regioselective intramolecular oxidative C-H amination from cyclic strained amides of aromatic amido-amidine systems (quinazolinones) has been developed. The amine functionalization of an aromatic C-H bond from a strained amide nitrogen involved in aromaticity has been a challenging work so far. The fusion of two heterocyclic cores, quinazolinone and phenanthridine, can occur in two different ways (linear and angular), but under the conditions reported here, only linear type isomer is exclusively produced. This approach provides a variety of substituted quinazolinone- and phenanthridine-fused derivatives in moderate to excellent yields. Moreover, such fused molecules show excellent fluorescent properties and have great potential to be a new type of fluorophores for the use in medicinal and material science.