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text:
Eureka or aha moments are what psychologists call "insight". This form of creativity is the sudden experience of comprehending something that you didn't understand before, connecting or combining concepts that form something new. This sudden clarity is also de!ned as imagination and is not only a building block of creative schools, but it also underpins creative problem-solving.
Insights have distinct features – since we can't demand them, we need to learn how to allow them.
This is why Design Thinking doesn't make you any more creative than a brainstorming session. While Design Thinking has processes that have a purpose, it is incorrect to presume they make you more imaginative and therefore creative.
Trying to control imagination is the opposite of what is necessary to generate original ideas. Imagine holding a proverbial gun to one's head to compel them to write a hit song – it's just not the way we work.
Another lesser-known feature of "insight" is that it is a visual skill. Even the very word "insight" is made up of a visual connotation "in sight".
As Neuroscientist and author of The Eureka Factor: Creative Insights and the Brain - Professor John Kounios writes:
"The other key feature of insights is that they yield, often literally, a different way of looking at things......That's why people often use expressions such as 'seeing things in a new light' or 'seeing things from a different angle' to describe insights"

subset: commoncrawl


text:
Bred by crossing OG Kush and San Fernando Valley OG Kush F3, Fire OG has a strong scent similar to Lemon Pledge and an effect that can last up to 3 hours. The plant has frost covered nuggets with red hairs, giving the appearance that it is on fire–where the name Fire OG comes from. Flowering time is generally 9-10 weeks.
Skywalker OG is a crossing between Skywalker and the OG Kush strain. As any crossing with OG Kush has proven to take a strain to its highest potential, this is definitely the case for Skywalker. Skywalker x OG Kush resulted in an Indica-dominant strain with a high THC ratio and its endorsed flavor profile. The pine of OG Kush combined with the fruitiness (lemon) of Skywalker has resulted in a well balanced sweet flavor with deep tones of noble wood. Skywalker OG seeds are really rewarding, producing big dense flowers with lots of resin. Want to Buy Skywalker OG Kush Online? They are easy to get started with, highly mold-resistant and will finish flowering within 60 days.
There are a few seed banks that have these seeds for sale. Some are looking for Reserva Privada Skywalker OG seeds from California USA or Apothecary Genetics, others want to buy Skywalker OG seeds from Amsterdam. Though there isn't much of a difference, all these breeders used the same lineage for their crossing, as we did. In case you wonder if Skywalker OG is the same as Skywalker OG Kush, yes, it is. We used the highest standards and beyond in creating this strain and we can ensure that we have the best Skywalker OG seeds for sale.
Buying the Skywalker OG seeds is a great choice. As mentioned earlier, Skywalker OG is an indica dominant strain with indica properties around 80%. The strain does well under many conditions and even in the colder regions it will flourish perfectly but when humidity levels are high the plant has an increased chance to mold. Indoors, low-stress training works well on this strain to increase its yield.
The strain is suitable for SOG and SCROG though to get the fullest out of one Skywalker OG feminized plant it needs a lot of space, especially when the topping is applied to encourage a more bushy stature. Skywalker OG feminized plants will yield pretty thick and heavy buds, supporting it with strong soil, nettings and rope will definitely help to get the most out of this strain.
Under perfect conditions, the yield of Skywalker OG strain can reach up to 700 gr/m2 outdoors. Indoors that will be around 600 gr/m2. On average the plant will yield up to 500 to 600 gr/m2.
Skywalker OG has a real short flowering time of 53 to 67 days. That is, with the huge yield taken into account, one of the great benefits of this strain. Of course, using the full flowering period of 67 days will ripe the buds to its best quality.
The THC levels of Skywalker OG will be around 19% to 21%. That is a pretty high THC level and that will reflect on the buds which are covered with THC crystals. Not the highest levels, but high enough for most.
Experiencing the taste of Skywalker OG is amazing and many different flavors come along. For most, it starts with a piney and kush flavor which slowly shifts towards lemon with a diesel tone. It is quite an experience tasting Skywalker OG feminized.
As you might expect from an Indica dominant strain which is high in THC, Skywalker OG (Kush) will provide a relaxed state of mind along with a euphoric feeling. A great painkiller with a warm and fuzzy feeling that will definitely create a broad smile.
fold up
|THC level
|CBD level
|80% Indica / 20% Sativa
|Skywalker x Og Kush
|Max yield indoor
|500 to 600 grams/m2
|Max yield outdoor
|600 to 700 grams/m2
|Height indoor
|80 to 120 cm
|Height outdoor
|120 to 180 cm
|Flowering time
|53 to 67 days
|Fungal Resistance
|Indoor, Outdoor, Greenhouse
|Temperate, Mediterranean, Arid, Tropical
|Diesel, Fruity, Lemon, Pine, Woody
|Calming, Euphoric, Happy, Relaxed, Uplifting
|SOG suitable
|SCROG suitable
|Select Quantity
1 Ounce, 1 Pound, Half Pound, Quater P


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When I first moved to Denver four years ago, I started looking for ways I could use my skills to give back to a worthy cause. Fresh out of college with a degree in marketing, I was reminded of my university's simple request to "ask more"—both of myself and of the business world I was about to take on. I started volunteering with a few nonprofits in the area, but none had a … Read More
COVID-19 Updates for our DSF Community
Dear friend of Denver Scholarship Foundation (DSF), A lot has changed over the past several days, but one thing has not: our commitment to our mission to inspire and empower Denver Public Schools students to enroll in and graduate from postsecondary institutions of higher education, by providing the tools, knowledge, and financial resources essential for success. As we continue to strategize the best ... Read More


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DALMUIR Library is offering residents a click-and-collect service to borrow books.
"Book to Borrow" launched on Monday and is operating 10am-4pm on weekdays only.
A maximum of five items can be requested remotely by telephone or online, and once available, a collection time will be arranged.
Residents can then safely collect their reserved items from tables which will be located within the main entrance.
All books will be quarantined for 72 hours after return before they are made available again, and items will no longer be transferred between branches until restrictions ease further.
Read more: Clydebank nursery install thermal body cams to ensure safety of children and staff
Councillor Ian Dickson, convener of corporate services, said: "We know how popular our library service is and we appreciate not all residents have been able to access our extensive online collection.
"We are keen to partially restart this service as we recognise the vital role our libraries play in the lives of our residents, especially those who are housebound or are shielding.
"At this time we are unable to offer other services from our branches but we will follow the guidance from the Scottish Government to ensure we are in a position to reopen when it is safe to do so."
When collecting, a face covering must be worn. Visit west-dunbarton.gov.uk/libraries to view the online catalogue and access the request form. Or call Dalmuir Library on 0141 562 2425.


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3 Ways To Boost Your Sites Rankings
Boosting the presence of your company in the Google search engine is a process that can take a significant amount of time. However, with some careful planning and the help of an SEO agency London service, it is possible to boost your ranking whilst maintaining your monthly budget.
Focus On Building A Strong Website
Building a strong website is a crucial part of Google rankings as a site that is not working properly will not rank well. Whether it is the loading speed, overall navigational errors or optimising for mobile, this can all aid in building the strong website.
In addition to building a strong website, it is important to focus on the keywords that you are looking to target. With content on the home page as well as products on other pages, you should consider the keywords to optimise rankings. In addition to the content on the page, it is important to look at the structure of the page. Though the content is crucial, the colour theme and the overall look of the site is just as important as this has the potential to sway the attention of the audience. By making the website look as professional as possible and provide effective navigation around it, this will ensure that your customers can find exactly what they need from you and can even get in contact with you moving forward as a result.
Publish Relevant Content
As well as making sure that the website is strengthened, it is important to ensure that you are publishing the relevant content. Not only will it aid you in capturing the attention of the target audience, but it will ensure that they get the information that they need from you. Not only does the content need to be fully optimised it should also be relevant to the page it is placed on.
Regardless of whether it is an FAQ page an about us page or product pages, the way you are writing and the length of the content should be kept as consistent as possible. By ensuring you have fully optimised your content, you are likely to not only improve your Google ranking but also capitalise on this newfound level of engagement.
Use Social media To Your Advantage
The final way that you can improve your ranking in Google search rankings is to make the most out of the social media. Whether this is posting across numerous different platforms or sharing your blogs, this can all aid you in linking to your website and boosting traffic. In addition to this, there is also the potential for you to use influencer marketing and competitions to boost engagement and make it easier than ever to boos traffic to your website.
Whether you are a small business looking to boost your presence in Google SERPs or you are looking to fully optimise your website for a larger company, there are several ways you can do so without spending a small fortune.


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- Home
- >
- Bearing
- >
- Timken Bearing
- >
- Timken NAO30X45X26 Bearing
Timken NAO30X45X26 Bearing
Offer price breaks when you order a larger quantify.
Leading time would be depends on our work efficiency and delivery schedule, usually within 2 business days.
Shipping: Ships in 2 business day
Timken NAO30X45X26 Description :
The bearing NAO30X45X26 manufactured by Timken can be ordered immediately from the bearings distributor GBS Bearing Co,Ltd. The bearing delivery is done directly from the stock, and in the event the bearings are not in stock, we shall inform you immediately related to the delivery term. For extra details on the NAO30X45X26 manufactured by Timken.
1) Commercial Bearings packaging: 1pc/plastic bag + color box + carton + pallet
2) Industrial Bearings packaging
a) plastic tube + carton + pallet
b) plastic bag +kraft paper + carton + pallet
3) According to the requirement of customers
1) T/T:30% deposit , 70% should be paid before shippment.
2) L/C at sight. (high bank charge, not suggest , but acceptable )
3) 100% Western Union in advance. (specially for air shipment or small amount)
1) Less than 45 KGS, we will send by express. ( Door to Door, Convenient )
2) Between 45 - 200 KGS, we will send by air transport. ( Fastest and safest, but expensive )
3) More than 200 KGS, we will send by sea. ( Cheapest, but long time )
TIMKEN | 14124/14274 Bearing Istanbul | 14124/14274
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Knit Socks
Collection by Sarah Schwab
Chili Pepper Socks
After knitting over one hundred pairs of socks I picked my favorite elements and combined them into my perfect sock. Give them a try and see if they do not soon become one of your favorites!
Sock It To Me Shoe Size to Sock Length Conversion Guide, Knitting Equipment
If you knit socks for gifts, " Sock It To Me Shoe Size to Sock Length Conversion Guide" offers information on making the perfect socks for everyone
techniques – Italian Dish Knits
Posts about techniques written by italiandishknits
Scatterby Socks
This sock is built on a easily remembered 4 stitch, 4 row pattern repeat that works up the top of the foot, and up the whole leg. The use of slipped stitches means this fabric has a nice, fitted and cozy feel, that still stretches to accommodate everything a good pair of socks should!
Knitting Tutorial: Picking Up Gusset Stitches
Learn how to pick up the gusset stitches on the side of a heel flap or band heel for hand knit socks.
Magician's Shortie Socks
Magic tricks are fun and engaging, just like this shortie sock pattern! And a magician's best trick is keeping you guessing 'how did they do it?' This fun lace design is worked over an easy to memorize 4-row repeat that may seem complicated, but really isn't, and will result in a fast knit that is sure to impress.
Marsh Felted Slippers
An easy felted slipper that knits up quickly. Works from the top of the ankle down and sewn up along the bottom of the foot.
Charlie Socks
Simple, little evergreens march in formation across the contrast-color toe of the Charlie socks. Add to this an easy triple-wedge heel, striped cuff, and a gorgeous tweed yarn, and you have a perfect sock for hiking a wooded trail or lounging by a crackling fire! Sized for you to knit for guys and gals.
Free pattern Friday: Self-Important Socks
(Photos: Deborah Kemball) These gorgeous socks were just published to Ravelry this week and are designed by one of our very own customers! Self-Important Socks by the lovely Deborah Kemball are knit with ARTFIL Belle and feature a two-colour rib, a simple fair isle motif, and the use of high-contrast hues to create socks that beg to be noticed! The…
Short Rows Tutorial
GREAT Short Row Heel Tutorial
Basic Socks on a tiny circular needle: A sock miracle!
***New**** I've created a gorgeous printable PDF of these instructions along with an original design for Canadian Juliet socks! Here is the link to find it: http://www.ravelry.com/patterns/library/smitten-socks Stranded patterns available too! Here is the link to find them: https://www.ravelry.com/designers/julie-coffey Size: Ladies medium Materials: ~300 yards fingerling weight sock yarn, pictured in the top photo is…
Sandal Knitting Patterns
Summer footwear knitting patterns. Many of the patterns are free
Make Your Heels Strong
The "Strong heel" was developed by Gerdine Crawford-Strong and first published in the Fall 2003 issue of Knitter's Magazine. This heel does not require picking up stitches along a heel flap. Because of the constructions it is not the snuggest fitting heel, which is why I have chosen to work it in a 2x2 rib instead of using the more common stockinette.
Knitting Socks with Afterthought Heels - Knit the whole sock so your pattern is consistent and come back to the heels last.
Sherwood Slippers Are Out!
Sherwood Slippers are toe-up, lightly-felted slippers for when you need just a little extra padding and warmth - perfect for w...


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Thank you for your interest in LegalBox. To setup your account, please follow the steps below:
- Visit https://legalboxsignup.coraltreetech.com/account to sign up. Select the type of account you'd like to create ("Account Owner" or "IT Administrator").
- Enter your email address and name, check the box for 'I am not a robot' captcha, then click submit. LegalBox will send an email with a link to create your password.
- Click the link to select a password for your account.
- Sign in with your email and the password you created.
- On the subsequent screens, read and accept the 'End User License Agreement', enter your company
name, and phone number.
- On the next screen create your folders:
- Review your Root Folder name. Root folder is used as a holding folder for all your company folders and
files, and needs to be unique across the LegalBox system.
- Next add your Shared folders, and invite users by entering their email addresses in the boxes provided.
Shared folders contain files to be shared.
- On the next screen, download the legal box security application, and install when prompted.
LegalBox installation is now complete. You can sign into your account, and upload files to be shared into
the shared folders.


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Business Development Coordinator (Back-end Role)
We're Digital Surgeons, an award-winning agency that focuses on three areas- Branding, Experience Design, and Demand Generation (multi-channel) for businesses in a variety of verticals.
We're looking for a Business Development Coordinator to provide support to our BD team and to foster data-driven decision making that will directly impact our top-line growth.
You should apply to this job if:
What you'll do:
What you bring:


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Hunters took to the field Saturday and Sunday across Northwest Montana for the opening of the 2017 general deer and elk season. At five northwest Montana check stations, a total of 3041 hunters check 278 white-tailed deer (132 were bucks), 4 mule deer, and 22 elk for a 10.0 percent rate of check station hunters with game. This compares to 3138 hunters and a 12.7 percent rate of hunters with game at check stations last year for opening weekend.
Overall, the number of hunters visiting check stations this year was slightly lower than last year, however, there was a lot a variability in participation at individual check stations. Only slightly fewer hunters visited the Highway 2 check station west of Kalispell compared to last year. Thirty-nine more hunters went through the Swan check station on Highway 83 compared to last year, but the Olney check station saw the biggest increase in hunter numbers, checking 82 more than in 2016. Both the Canoe Gulch and Thompson Falls check stations saw decreases in hunter visiting check stations. According to Bruce Sterling, the FWP biologist in Thompson Falls, the numbers were unusually low. "I haven't had this few hunters through the check station in a really long time". Poor weather on Sunday, hunters deciding to go to other areas are a few of the possible reasons for seeing fewer hunters in some areas compared to others.
The Swan and Olney check stations had the strongest results with 15.2 and 11.7 percent of the hunters with game. Mule deer harvest was down considerably from the previous 7 years. "We don't think mule deer numbers have changed significantly over last year" says Neil Anderson, FWP Region 1 Wildlife Manager. "We still have 5 weeks to of the general season left. The differences we observed in both hunter numbers and in some game numbers, like mule deer, may level out over the remainder of the season. Overall, the percentage of people with game is really quite good for northwest Montana."
Hunters are reminded that the ability to harvest antlerless whitetails on a general license extend through this Friday, October 27th. Starting Saturday, October 28th only antlered buck whitetails are legal on a general license, until the last week of the season. From November 20-26th, hunters can harvest an antlerless whitetail on private property (excluding corporate timber lands) on a general license. Apprentice and youth hunters under the age of 16 can harvest antlerless whitetails all season long.
Mule deer are buck only and elk are brow-tine bull only. Check the Montana hunting regulations for the district you plan to hunt.
Brett French Presents: Revival of a Classic
By angelamontana
By Montana Grant
Central to Eastern MT Fishing Report 8.5.20
FWP seeks public comment on proposed fishing dock project at Black Sandy State Park
Fishing restrictions enacted for several rivers due to warm temps
Fish and Wildlife Commission to hear petitions regarding River Recreation on the Madison River at Aug. 13 meeting
Snagging Paddlefish in the Missouri River [VIDEO]
REMINDER: Fish and Wildlife Commission to meet August 13
Bird Island closed to public, FWP will not suppress wildfire there
By Moosetrack Megan
Baldy Mountain Fire Closure Order Enacted
Upland Game Bird Enhancement Program Projects Access Guide available online starting Aug. 10
Block Management Program information available starting Aug.10
Antelope drawing set for Aug. 6; no 900-20 archery surplus tags will be available
Small dams in small creeks can have big consequences
2020 Montana boat validation decals required
FWP bans fires at Wheatland County properties
Huge Bull Elk Bugling — Who's Ready for the 2020 Season? [VIDEO]
First Walleye! [VIDEO]
FWP to conduct rotenone treatment of North Fork of Spanish Creek
Grizzly killed due to cattle depredation
A Montana Gem – Smith River
Helena Area Reservoirs Fishing Report 8.3.20
Watch Saturday's episode of MORS here!


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Taste test: This box of gummies was unusual in that the pieces were quite a bit larger than your usual gummy candies, with sizes ranging from about half an inch to and inch and a half, depending on the shape.
There were four Monopoly shapes inside: hotel, hat, dog and car, with some kinds appearing in multiple colors. The box had a handy color key identifying the flavor/color correspondence of the strawberry (red), watermelon (green), orange (orange) and mixed berries (blue) types. The pieces looked quite nice, authentically replicating the iconic monopoly shapes with an attractive translucent appearance. They tasted good too, with good fruit flavor and a soft, moist texture. Very nice!
Shop: Buy snacks on Amazon #ad
Smell test: Good fruity smell.
From the package: "Made in China" ... "This Product is manufactured in a nut free facility." ... "Remove all packing before giving to a child."
Online store: Buy snacks on Amazon #ad
Company: Au'some Candies Inc.
Categories for this snack:
- Fruit Snacks (423 snacks)
- Snacks Shaped Like Things (379 snacks)
- Gummy Candies (59 snacks)
This snack was discovered by Jeremy at Dollar Tree. Review published .
Most popular reviews
- Moon Lodge The Whole Shabang Potato Chips
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Latest reviews
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Still hungry? Check out the 100 latest reviews
What We're Eating
- Lay's gets a new logo
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Watch: Insane Rolling Gun Battle On Mexican Streets
An insane video reportedly out of Nuevo Laredo, Tamaluipas, Mexico, recorded on July 3, 2020 shows the Mexican military in a mounted, high speed gun battle with sicarios of the Northeast Cartel.
The incident reportedly resulted in the deaths of 16 cartel members. In the gruesome aftermath photos, the dead sicarios can be seen wearing matching military uniforms with advanced kit that included chest racks and ballistic helmets.
Author: Will
Source: Funker530: Insane Video Shows High Speed Rolling Gun Battle On Mexican Streets


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Toyota RAV4: Key battery
Replace the battery with a new one if it is discharged.
■ You will need the following items:
● Flathead screwdriver (To prevent damage to the key, cover
the tip of the screwdriver with a rag.)
● Small Flathead screwdriver
● Lithium battery CR2016 (vehicles without smart key system) or CR1632 (vehicles with smart key system)
■ Replacing the battery (vehicles without smart key system)
Remove the cover.
Remove the module.
Open the case cover using a coin protected with tape etc. and remove the depleted battery. Insert a new battery with the "+" terminal facing up.
■ Replacing the battery (vehicles with smart key system)
Take out the mechanical key.
Remove the cover.
Remove the depleted battery. Insert a new battery with the "+" terminal facing up.
■If the key battery is depleted
The following symptoms may occur.
●The smart key system and wireless remote control will not function
●The operational range is reduced.
■Use a CR2016 (vehicles without smart key system) or CR1632 (vehicles with smart key system) lithium battery
●Batteries can be purchased at your Toyota dealer, jewelers, or camera
●Replace only with the same or equivalent type recommended by your Toyota dealer.
●Dispose of used batteries according to the local laws.
■Removed battery and other parts
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We report on the light-switch behaviour of two head-to-tail expanded bipyridinium species as a function of their interaction with calf thymus DNA and polynucleotides. In particular, both DNA and polynucleotides containing exclusively adenine or guanine moieties quench the luminescence of the fused expanded bipyridinium species. This behaviour has been rationalized demonstrating that a reductive photoinduced electron transfer process takes place involving both adenine or guanine moieties. The charge separated state so produced recombines in the tens of picoseconds. These results could help in designing new organic substrates for application in DNA probing technology and lab on chip-based sensing systems.
AssuntosSondas de DNA/química , DNA/análise , Corantes Fluorescentes/química , Imagem Óptica , Compostos de Piridínio/química , Animais , Bovinos , Sondas de DNA/síntese química , Corantes Fluorescentes/síntese química , Estrutura Molecular , Oxirredução , Compostos de Piridínio/síntese química , Espectroscopia de Luz Próxima ao Infravermelho , Raios Ultravioleta
A novel panel of oximes were synthesized, which have displayed varying degree of reactivation ability towards different organophosphorus (OP) modified cholinesterases. In the present article, we report a comparative reactivation profile of a series of quaternary pyridinium-oximes for electric eel acetylcholinesterase (EEAChE) inhibited by the organophosphorus (OP) inhibitors methyl paraoxon (MePOX), ethyl paraoxon (POX; paraoxon) and diisopropyl fluorophosphate (DFP) that are distinguishable as dimethoxyphosphoryl, diethoxyphosphoryl and diisopropoxyphosphoryl AChE-OP-adducts. Most of the 59-oximes tested led to faster and more extensive reactivation of MePOX- and POX-inhibited EEAChE as compared to DFP-modified EEAChE. All were effective reactivators of three OP-modified EEAChE conjugates showing 18-21% reactivation for DFP-inhibited AChE and ≥45% reactivation for MePOX- and POX-inhibited EEAChE. Oximes 7 and 8 showed kr values better than pralidoxime (1) for DFP-inhibited EEAChE. Reactivation rates determined at different inhibition times showed no significant change in kr values during 0-90â¯min incubation with three OPs. However, a 34-72% decrease in kr for MePOX and POX and > 95% decrease in kr for DFP-inhibited EEAChE was observed after 24â¯h of OP-exposure (aging).
AssuntosAcetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Reativadores da Colinesterase/farmacologia , Compostos Organofosforados/química , Oximas/farmacologia , Compostos de Piridínio/farmacologia , Animais , Reativadores da Colinesterase/síntese química , Reativadores da Colinesterase/química , Desenho de Fármacos , Electrophorus , Simulação de Acoplamento Molecular , Estrutura Molecular , Agentes Neurotóxicos/química , Intoxicação por Organofosfatos/enzimologia , Intoxicação por Organofosfatos/prevenção & controle , Oximas/síntese química , Oximas/química , Compostos de Piridínio/síntese química , Compostos de Piridínio/química
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated ß-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N'-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated ß-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson's. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it.
AssuntosTécnicas de Química Sintética , Compostos de Piridínio/síntese química , Fenômenos Químicos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos de Piridínio/química , Compostos de Piridínio/isolamento & purificação
A series of novel gemini pyridinium surfactants with different alkyl chains were synthesized and characterized. The surface properties and aggregation behavior of the gemini surfactants in solution were studied. The gemini pyridinium salts exhibit higher surface activity than quaternary ammonium salts and can form vesicles above critical micellization concentration (CMC). The antimicrobial performance of these surfactants against E. coli was investigated and compared with those of quaternary ammonium salts. Alkyl chain length has a significant effect on the antimicrobial activity of the gemini surfactants, and the surfactant with decyl group showed more effective antimicrobial activity than quaternary ammonium salts. The high cationic charge density on the polar head group and the strong adsorption tendency confer relatively high antimicrobial of the gemini surfactants.
AssuntosAntibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Compostos de Piridínio/farmacologia , Tensoativos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Escherichia coli/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Compostos de Piridínio/síntese química , Compostos de Piridínio/química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Propriedades de Superfície , Tensoativos/síntese química , Tensoativos/química
A novel ratiometric fluorescence probe for hypochlorous acid was constructed by coumarin and pyridinium fluorophore based on the Forster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) platform. In this ICT/FRET system, the energy transfer efficiency is high to 94.3%. Moreover, the probe could respond to hypochlorous acid with high selectivity and sensitivity, and exhibited a large Stokes shift. It was interesting to find that the probe could recognize hypochlorous acid via a new mechanism, in which the α-position of carbonyl group was oxidized to form a diketone derivative. More importantly, the probe was successfully applied to the ratiometric imaging of both exogenous and endogenous hypochlorous acid in living RAW 264.7â¯cells, with low toxicity and high photo-stability.
AssuntosCumarínicos/química , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Ácido Hipocloroso/metabolismo , Compostos de Piridínio/química , Animais , Cumarínicos/síntese química , Cumarínicos/efeitos da radiação , Desenho de Fármacos , Fluorescência , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Concentração de Íons de Hidrogênio , Luz , Limite de Detecção , Camundongos , Imagem Óptica/métodos , Compostos de Piridínio/síntese química , Compostos de Piridínio/efeitos da radiação , Células RAW 264.7
Small molecules emitting in the NIR for tracking mitochondrial pH alteration with super-resolution are expected to play an essential role in biomedical applications. Herein, two small molecules based on pyridinium salt (P1 and P2) have been synthesized and systematically investigated. It was found that pyridinium salts P1 and P2 emitted in the NIR (about 610â¯nm), which could detect pH changes from 2.0 to 11.0 with good linearity and high sensitivity. Importantly, P2 could precisely target cellular mitochondria in a real-time manner under stimulated emission depletion (STED). These results implied a chemical strategy with a potential application in super-resolution imaging and mitochondrial pH determination.
AssuntosMitocôndrias/química , Compostos de Piridínio/química , Bibliotecas de Moléculas Pequenas/química , Cristalografia por Raios X , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Microscopia de Fluorescência , Modelos Moleculares , Estrutura Molecular , Compostos de Piridínio/síntese química , Teoria Quântica , Bibliotecas de Moléculas Pequenas/síntese química
The diblock copolymer polystyrene-block-poly(N-methyl 4-vinylpyridine iodide) (PS-b-P4VPQ) with the molecular weight of PS 3.5 × 103 g/mol and P4VPQ 11.6 × 103 g/mol forms core-shell polymer micelles in aqueous solution. The cationic brush shell of the polymer micelle can be used to accommodate hydrophilic drugs and biomolecules, such as DNA, for biomedical applications. It is essential to understand how biomolecules are adsorbed within the brush layer. Here we investigated the interaction of the cationic brush of the polymer micelle with DNA by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). It is found when adding only relatively small amounts of on average 30 base pairs (bp) DNA, at 19.6 and 39.2 µM for 0.1 mM PS-b-P4VPQ, most of the polymer micelle/DNA complexes remain well dispersed. The brush layer of the polymer micelles are slightly swelled due to the adsorption of DNA within the brush layer. When the DNA concentration is increased to 58.8 µM or higher, the polymer micelle/DNA complexes form closely packed agglomerates. At high DNA concentrations, some adsorbed DNA will start to build up at the edge or surface of the brush layer which could induce aggregation of the polymer micelle/DNA complexes. This means that it is possible to prepare mostly dispersed polymer/DNA complexes by keeping the DNA concentration below the aggregation concentration. The well dispersed polymer micelle/DNA complexes are advantageous for many DNA related biomedical applications.
AssuntosDNA/química , Micelas , Poliestirenos/química , Compostos de Piridínio/química , Adsorção , Cátions , Poliestirenos/síntese química , Compostos de Piridínio/síntese química , Espalhamento a Baixo Ângulo , Difração de Raios X
Enzymatic 18O exchange, the well-established approach in comparative proteomics, has some disadvantages such as back exchange of labeled oxygen and overlapping the peak of a labeled peptide with isotopic peaks of an unlabeled one. Herein we demonstrated a simple procedure in which samples digested with a trypsin (with and without H218O) were reacted with unlabeled and quadrupled 13C-labeled pyrylium salt respectively which results in formation of pyridinium cations. Thus, each isobarically labeled peptide containing zero or four 13C atoms in the mass reporter group, during tandem MS/MS forms an unique reporter ion useful for a relative quantitation. Such a sample treatment improves the signal to noise ratio, reduces overlapping of the isotopic peaks and completely eliminates the back exchange problem.
AssuntosMarcação por Isótopo/métodos , Oligopeptídeos/química , Fragmentos de Peptídeos/química , Proteômica/métodos , Piranos/química , Espectrometria de Massas em Tandem/métodos , Proteínas Sanguíneas/síntese química , Proteínas Sanguíneas/química , Isótopos de Carbono/química , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/síntese química , Peptídeos e Proteínas de Sinalização Intracelular/química , Proteínas de Membrana/síntese química , Proteínas de Membrana/química , Oligopeptídeos/síntese química , Isótopos de Oxigênio/química , Fragmentos de Peptídeos/síntese química , Compostos de Piridínio/síntese química , Compostos de Piridínio/química , Albumina Sérica Humana/síntese química , Albumina Sérica Humana/química , Tripsina/química
Nucleus imaging is of great importance for understanding cellular processes of genetic expression, proliferation and growth, etc. Although many nucleic-acid selective dyes for nucleus staining are available, few of them meet multiple standards. Herein, we report a cationic fluorescence dye FTI that possesses visible light excitation (436â¯nm), orange emission (571â¯nm) and a large Stokes shift (~135â¯nm) for nucleic-acid staining. FTI displays an obvious and sensitive fluorescent response to DNA in vitro with a 6.4-fold quantum yield increasing. Co-staining and nucleic acid digest experiments in live cells demonstrate that FTI exhibits an unexpected selectivity for the nucleolus of the cells due to the stronger affinity to RNA than DNA. Because of good photostability and low cytotoxicity, FTI can accomplish a promising stain for DNA recognition in vitro and nucleolus-specific imaging in cancer cells.
AssuntosNucléolo Celular/metabolismo , DNA/metabolismo , Fluorenos/química , Corantes Fluorescentes/química , Compostos de Piridínio/química , Estabilidade de Medicamentos , Fluorenos/síntese química , Fluorenos/efeitos da radiação , Fluorenos/toxicidade , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/efeitos da radiação , Substâncias Intercalantes/toxicidade , Luz , Microscopia Confocal , Microscopia de Fluorescência , Compostos de Piridínio/síntese química , Compostos de Piridínio/efeitos da radiação , Compostos de Piridínio/toxicidade
BACKGROUND: This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives. OBJECTIVE: In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated. METHODS: Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death. RESULTS: Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods. CONCLUSION: In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.
AssuntosAntineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Imidazóis/farmacologia , Compostos de Piridínio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Imidazóis/síntese química , Imidazóis/química , Estrutura Molecular , Compostos de Piridínio/síntese química , Compostos de Piridínio/química , Relação Estrutura-Atividade
A novel series of benzylpyridinium-based benzoheterocycles (benzimidazole, benzoxazole or benzothiazole) were designed as potent acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The title compounds 4a-q were conveniently synthesized via condensation reaction of 1,2-phenylenediamine, 2-aminophenol or 2-aminothiophenol with pyridin-4-carbalehyde, followed by N-benzylation using various benzyl halides. The results of in vitro biological assays revealed that most of them, especially 4c and 4g, had potent anticholinesterase activity comparable or more potent than reference drug, donepezil. The kinetic study demonstrated that the representative compound 4c inhibits AChE in competitive manner. According to the ligand-enzyme docking simulation, compound 4c occupied the active site at the vicinity of catalytic triad. The compounds 4c and 4g were found to be inhibitors of Aß self-aggregation as well as AChE-induced Aß aggregation. Meanwhile, these compounds could significantly protect PC12 cells against H2O2-induced injury and showed no toxicity against HepG2 cells. As multi-targeted structures, compounds 4c and 4g could be considered as promising candidate for further lead developments to treat Alzheimer's disease.
AssuntosCompostos Heterocíclicos com 2 Anéis/farmacologia , Fármacos Neuroprotetores/farmacologia , Compostos de Piridínio/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Animais , Butirilcolinesterase/metabolismo , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/toxicidade , Desenho de Fármacos , Electrophorus , Compostos Heterocíclicos com 2 Anéis/síntese química , Compostos Heterocíclicos com 2 Anéis/metabolismo , Compostos Heterocíclicos com 2 Anéis/toxicidade , Cavalos , Humanos , Peróxido de Hidrogênio/farmacologia , Cinética , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Multimerização Proteica/efeitos dos fármacos , Compostos de Piridínio/síntese química , Compostos de Piridínio/metabolismo , Compostos de Piridínio/toxicidade , Ratos , Torpedo
A series of pentamethinium salts with benzothiazolium and indolium side units comprising one or two positive charges were designed and synthesized to determine the relationships among the molecular structure, charge density, affinity to sulfated polysaccharides, and biological activity. Firstly, it was found that the affinity of the pentamethinium salts to sulfated polysaccharides correlated with their biological activity. Secondly, the side heteroaromates displayed a strong effect on the cytotoxicity and selectivity towards cancer cells. Finally, doubly charged pentamethinium salts possessing benzothiazolium side units exhibited remarkably high efficacy against a taxol-resistant cancer cell line.
AssuntosAntineoplásicos/farmacologia , Glicosaminoglicanos/metabolismo , Indóis/farmacologia , Compostos de Piridínio/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Benzotiazóis/síntese química , Benzotiazóis/química , Benzotiazóis/metabolismo , Benzotiazóis/farmacologia , Células CHO , Linhagem Celular Tumoral , Cricetulus , Desenho de Fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Indóis/síntese química , Indóis/química , Indóis/metabolismo , Ligantes , Estrutura Molecular , Compostos de Piridínio/síntese química , Compostos de Piridínio/química , Compostos de Piridínio/metabolismo , Ésteres do Ácido Sulfúrico/metabolismo
Two cationic δ,δ'diazacarbazoles, 1Methyl5Hpyrrolo[3,2b:4,5b']dipyridinium iodide (MPDPI) and 1,5Dimethyl5Hpyrrolo[3,2b:4,5b']dipyridinium iodide (DPDPI), were devised and synthesized. Through characterizations of the interactions between DNA and the two δ,δ'diazacarbazoles by various spectroscopy means, the strong interactions between the two compounds and double-strand DNA have been observed and the interaction types and mechanisms were explored. UV-Vis and fluorescent data have shown the big changes of DNA in the presence of either of the two compounds, demonstrating that both of the δ,δ'diazacarbazoles can bind to DNA tightly, and high ionic strength decreased the intercalative interactions. The UV-Vis and fluorescence of dsDNA in the presence of DPDPI showed more profound changes than those in the presence of MPDPI, due to CH3 (in the structure of DPDPI) taking place of H (in the structure of MPDPI) at the position of 5NH. And the circular dichroism (CD) spectra of CT-DNA and atomic force microscopy (AFM) results indicated more compacted conformation of DNA in the presence of DPDPI than MPDPI, implying that DPDPI has a more significant effect on DNA conformations than MPDPI. Most interestingly, fluorescence enhancement of cationic δ,δ'diazacarbazoles occurred in the presence of DNA. With ionic strength increasing, the intercalative interactions between δ,δ'diazacarbazoles and DNA were weakened, but δ,δ'diazacarbazoles-DNA complexes showed enhanced fluorescence, which indicated that there are other interactions present at high ionic strength. Furthermore, laser confocal fluorescence microscopy results proved that DPDPI was membrane-permeable and stained living cells.
AssuntosCarbazóis/química , DNA/metabolismo , Corantes Fluorescentes/metabolismo , Compostos de Piridínio/metabolismo , Pirróis/metabolismo , Cátions , Permeabilidade da Membrana Celular , Dicroísmo Circular , DNA/química , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Masculino , Microscopia de Força Atômica , Microscopia Confocal/métodos , Conformação de Ácido Nucleico , Concentração Osmolar , Células PC-3 , Compostos de Piridínio/síntese química , Compostos de Piridínio/química , Pirróis/síntese química , Pirróis/química , Espectrofotometria Ultravioleta
Multi-triggered DNA/bipyridinium dithienylethene (DTE) hybrid carboxymethyl cellulose (CMC)-based hydrogels are introduced. DTE exhibits cyclic and reversible photoisomerization properties, switching between the closed state (DTEc), the electron acceptor, and the open isomer (DTEo) that lacks electron acceptor properties. One system introduces a dual stimuli-responsive hydrogel containing CMC chains modified with electron donor dopamine sites and self-complementary nucleic acids. In the presence of DTEc and the CMC scaffold, a stiff hydrogel is formed, cooperatively stabilized by dopamine/DTEc donor-acceptor interactions and by duplex nucleic acids. The cyclic and reversible formation and dissociation of the supramolecular donor-acceptor interactions, through light-induced photoisomerization of DTE, or via oxidation and subsequent reduction of the dopamine sites, leads to hydrogels of switchable stiffness. Another system introduces a stimuli-responsive hydrogel triggered by one of three alternative signals. The stiff, multi-triggered hydrogel consists of CMC chains cross-linked by dopamine/DTEc donor-acceptor interactions, and by supramolecular K+-stabilized G-quadruplexes. The G-quadruplexes are reversibly separated in the presence of 18-crown-6 ether and reformed upon the addition of K+. The stiff hydrogel undergoes reversible transitions between high-stiffness and low-stiffness states triggered by light, redox agents, or K+/crown ether. The hybrid donor-acceptor/G-quadruplex cross-linked hydrogel shows shape-memory and self-healing features. By using three different triggers and two alternative memory-codes, e.g., the dopamine/DTEc or the K+-stabilized G-quadruplexes, the guided shape-memory function of the hydrogel matrices is demonstrated.
AssuntosDNA Complementar/química , Hidrogéis/química , Compostos de Piridínio/química , Carboximetilcelulose Sódica/síntese química , Carboximetilcelulose Sódica/química , Éteres de Coroa/química , DNA Complementar/síntese química , DNA Complementar/genética , Dopamina/síntese química , Dopamina/química , Quadruplex G , Hidrogéis/síntese química , Isomerismo , Hibridização de Ácido Nucleico , Oxirredução , Fenômenos Físicos , Compostos de Piridínio/síntese química , Compostos de Piridínio/efeitos da radiação , Raios Ultravioleta
Voltage sensitive dyes (VSDs) are used for in vitro drug screening and for imaging of patterns of electrical activity in tissue. Wide application of this technology depends on the availability of sensors with high sensitivity (percent change of fluorescence per 100 mV), high fluorescence quantum yield, and fast response kinetics. A promising approach uses a two-component system consisting of anionic membrane permeable quenchers with fluorophores labeling one side of the membrane; this produces voltage-dependent fluorescence quenching. However, the quencher must be kept at low concentrations to minimize pharmacological effects, thus limiting sensitivity. By developing tethered bichromophoric fluorophore quencher (TBFQ) dyes, where the fluorophore and quencher are covalently connected by a long hydrophobic chain, the sensitivity is maximized and is independent of VSD concentration. A series of 13 TBFQ dyes based on the aminonaphthylethenylpyridinium (ANEP) fluorophore and the dipicrylamine anion (DPA) quencher have been synthesized and tested in an artificial lipid bilayer apparatus. The best of these, TBFQ1, shows a 2.5-fold change in fluorescence per 100 mV change in membrane potential, and the response kinetics is in the 10-20 ms range. This sensitivity is an order of magnitude better than that of commonly used VSDs. However, the fluorescence quantum yield is only 1.6%, which may make this first generation of TBFQ VSDs impractical for in vivo electrical imaging. Nevertheless, the design principles established here can serve as foundation for improved TBFQ VSDs. We believe this approach promises to greatly enhance our ability to monitor electrical activity in cells and tissues.
AssuntosCorantes Fluorescentes/química , Picratos/química , Compostos de Piridínio/química , Técnicas Eletroquímicas/métodos , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/síntese química , Bicamadas Lipídicas/química , Potenciais da Membrana , Estrutura Molecular , Compostos de Piridínio/síntese química
The current standard therapy to counteract organophosphate intoxication is not effective in equal measure against all types of organophosphorus compounds (OPCs), as the outcome of oxime-induced reactivation of inactivated acetylcholinesterase (AChE) strongly depends on the particular OPC. In case the reactivation is insufficient, acetylcholine concentrations that rise to pathophysiological levels force the nicotinic acetylcholine receptor (nAChR) into a desensitized state and hence a functionally inactive state. As a consequence, neurotransmission is irreversibly disrupted at the neuromuscular junction. Previous electrophysiological studies identified the symmetric bispyridinium compound 1,1'-(propane-1,3-diyl)bis[4-(tert-butyl)pyridin-1-ium] diiodide (MB327) as a re-sensitizer of the desensitized nAChR. MB327 is thereby capable of restoring the functional activity. Very recently, in silico modeling studies suggested non-symmetric derivatives of MB327 as potential re-sensitizers with enhanced binding affinity and thus possible enhanced efficacy. In this study, 26 novel non-symmetric bispyridinium compounds and related derivatives were synthesized. For the synthesis of the highly polar target compounds in sufficient quantities, newly developed and highly efficient two-step procedures were used. Compounds were characterized in terms of their binding affinity toward the MB327 binding site at the nAChR using recently developed mass spectrometry (MS) Binding Assays. Regarding structure-affinity relationships at the MB327 binding site, the presence of two quaternary aromatic nitrogen centers as well as pyridinium systems with a tert-butyl group at the 4-position or a NMe2 group at the 3- or 4-positions appeared to be beneficial for high binding affinities.
AssuntosCompostos de Piridínio/síntese química , Compostos de Piridínio/metabolismo , Receptores Nicotínicos/metabolismo , Animais , Sítios de Ligação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Torpedo
First-line medical treatment against nerve agents consists of co-administration of anticholinergic agents and oxime reactivators, which reactivate inhibited AChE. Pralidoxime, a commonly used oxime reactivator, is effective against some nerve agents but not against others; thus, new oxime reactivators are needed. Novel tacrine-pyridinium hybrid reactivators in which 4-pyridinealdoxime derivatives are connected to tacrine moieties by linear carbon chains of different lengths (C2-C7) were prepared (Scheme 1, 5a-f). Their binding affinities to electric eel AChE were tested because oximes can inhibit free AChE, and the highest AChE activity (95%, 92%, and 90%) was observed at 1⯵M concentrations of the oximes (5a, 5b, and 5c, respectively). Based on their inhibitory affinities towards free AChE, 1⯵M concentrations of the oxime derivatives (5) were used to examine reactivation of paraoxon-inhibited AChE. Reactivation ability increased as the carbon linker chains lengthened (nâ¯=â¯2-5), and 5c and 5d showed remarkable reactivation ability (41%) compared to that of 2-PAM (16%) and HI-6 (4%) against paraoxon-inhibited electric eel AChE at 1⯵M concentrations. Molecular docking simulation showed that the most stable binding free energy was observed in 5c at 73.79â¯kcalâ mol-1, and the binding mode of 5c is acceptable for the oxygen atom of oximate to attack the phosphorus atom of paraoxon and reactivate paraoxon-inhibited eel AChE model structure.
AssuntosAcetilcolinesterase/metabolismo , Reativadores da Colinesterase/química , Reativadores da Colinesterase/farmacologia , Compostos de Piridínio/química , Compostos de Piridínio/farmacologia , Tacrina/química , Tacrina/farmacologia , Animais , Inibidores da Colinesterase/farmacologia , Reativadores da Colinesterase/síntese química , Electrophorus , Simulação de Acoplamento Molecular , Paraoxon/farmacologia , Compostos de Piridínio/síntese química , Tacrina/síntese química
A novel pyridine-based organic conjugated molecule (NCPy) has been successfully synthesized and converted into an organic pyridinium salt (NCPy-salt). Highly oriented organic nanofibers and high-quality films were obtained by transforming the molecule to a salt form. This transformation also resulted in a unique ternary resistive switching memory behavior.
AssuntosCarbazóis/química , Nanofibras/química , Naftalimidas/química , Compostos de Piridínio/química , Sais/química , Carbazóis/síntese química , Condutividade Elétrica , Modelos Químicos , Naftalimidas/síntese química , Compostos de Piridínio/síntese química , Teoria Quântica , Sais/síntese química
A mitochondrial-targeted pH fluorescent probe 4-(2-(6-hydroxynaphthalen-2-yl)vinyl)-1-methylpyridin-1-ium was facilely synthesized via the carbon-carbon double bond bridging of 6-hydroxy-2-naphthaldehyde and 1,4-dimethylpyridinium iodide salt. The probe exhibited remarkable pH-dependent behavior in the linear range of 7.60-10.00, with a pKa value of 8.85 ± 0.04 near mitochondrial pH. A significantly large Stokes shift of 196 nm was obtained, which reduces the interference of excitation light. Application of the probe in live HepG2 cells indicated that the probe had excellent mitochondrial targeting ability and was successfully used to visualize mitochondrial pH fluctuations in live cells.
AssuntosCorantes Fluorescentes/química , Mitocôndrias/metabolismo , Naftalenos/química , Compostos de Piridínio/química , Estabilidade de Medicamentos , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Luz , Microscopia Confocal , Microscopia de Fluorescência , Naftalenos/síntese química , Naftalenos/efeitos da radiação , Naftalenos/toxicidade , Compostos de Piridínio/síntese química , Compostos de Piridínio/efeitos da radiação , Compostos de Piridínio/toxicidade
A novel series of 30 symmetric bispyridinium and related N-heteroaromatic bisquaternary salts with a propane-1,3-diyl linker was synthesized and characterized for their binding affinity at the MB327 binding site of nicotinic acetylcholine receptor (nAChR) from Torpedo californica. Compounds targeting this binding site are of particular interest for research into new antidotes against organophosphate poisoning, as therapeutically active 4-tert-butyl-substituted bispyridinium salt MB327 was previously identified as a nAChR re-sensitizer. Efficient access to the target compounds was provided by newly developed methods enabling N-alkylation of sterically hindered or electronically deactivated heterocycles exhibiting a wide variety of functional groups. Determination of binding affinities toward the MB327 binding site at the nAChR, using a recently developed mass spectrometry (MS)-based Binding Assay, revealed that several compounds reached affinities similar to that of MB327 (pKi =4.73±0.03). Notably, the newly prepared lipophilic 4-tert-butyl-3-phenyl-substituted bispyridinium salt PTM0022 (3 h) was found to have significantly higher binding affinity, with a pKi value of 5.16±0.07, thus representing considerable progress toward the development of more potent nAChR re-sensitizers.


text:
Lord Balaji, venkatesh, govinda, venkateswara, vishnu
Hare Krishna
Krishna - The Source of Everything !! Dear reader's welcome to the site iandKṛṣṇa. Through this website it's our endeavor to give chance to every human being to understand God's creation, in other words, to provide insight into the
"Dança Cigana"
("mad", from vāyu - "air" or "wind")....... Where shall I meet him, the Man of my Heart? He is lost to me and I seek him wandering from land to land.
✨ SHRI KRISHNA GOVINDA ॐ ✨ "The Supreme Personality of Godhead, who is inconceivably opulent, who is devoid of all material names, forms and pastimes, and who is all-pervading, is especially merciful...
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radha vavabha
Shri Krishna
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text: On 16 May 1943, nineteen Lancaster aircraft from the RAF's 617 Squadron set off to attack the great dams in the industrial heart of Germany. Flying at a height of 60ft, they dropped a series of bombs which bounced across the water and destroyed two of their targets, thereby creating a legend. The one-off operation combined an audacious method of attack, technically brilliant flying and visually spectacular results.But while the story of Operation Chastise is well known, most of the 133 'Dambusters' who took part in the Dams Raid have until now been just names on a list. They came from all parts of the UK and the Commonwealth and beyond, and each of them was someone's son or brother, someone's husband or father. This is the first book to present their individual stories and celebrate their skill, heroism and, for many, sacrifice.


text:
STEVEN MVULA, Lusaka
VICE-PRESIDENT Inonge Wina says the effectiveness of a country's legal system is measured by the level of access to justice for the poorest and most vulnerable in society.
Mrs Wina said she is glad that Zambia is one of the first countries in Africa to recognise the need to improve access to justice for people at the grassroots.
"In 1974, the Commission for Investigations was established as Zambia's Ombudsman's office and the office of the Investigator General, established by the Constitution as the office of the Ombudsman in Zambia,†she said.
Mrs Wina said the Commission for Investigations was recently transformed into the office of the Public Protector, effectively converting it into a Parliamentary Ombudsman.
Mrs Wina was speaking yesterday when she officiated at the Ombudsman Mediators Association (AOMA) and the International Ombudsman Institute (IOI) member countries' meeting at Mulungushi International Conference Centre in Lusaka.
She said access to justice by the poor and vulnerable is dear to her heart because she was once a human rights activist.
"The barometric reading may be at its lowest point due to various socio-economic and political difficulties that the continent is facing. However, throughout the African continent, there is a revolution and a great political will to ensure that access to justice for the majority of the African people is both attainable and attained,†Mrs Wina said.
She said Zambia will always support efforts aimed at promoting democracy and the rule of law.
Zambia's legal system poor-friendly – Wina
STEVEN MVULA, Lusaka


text:
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2020-07-12 16:53:53
Work well, sticky enought , will see how long it can stay fixed
2019-09-11 05:33:02
The delivery was very quick and exactly as described
2015-05-13 05:43:47
ordered 2x 1M, came in quickly, but are useless since they came in the big plastic envelope, because of whichthey got all bent through transit and as I learned they do not look good on glass once bent, lines from bent spots stay on it. Wanted to use for kitchen glass cabinet doors. Should be sent in hard tube instead.
2016-08-11 16:53:29
For best results: 1. Take the time to clean the surface properly before applying. 2. Plan out your use in advance. 3. Get some extra in case you make a mistake. It's so simple to do yourself.
2016-04-04 14:39:08
@banggood Would like a refund or another PVC frosted glass sent out This time in a Tube for protection please. The ends are damaged. Product ID: 970953
2015-11-18 12:08:24
Objednával jsem 3x 1m ... jedna rolička měla 98 cm, druhá 96 cm a třetí 97 cm. Přišlo to v měkkém obalu a při přepravě byly 2 role zlomené. Naštěstí jsem lepil okno a tam mi to nevadí. Vytvoří téměř dokonalý zvhled "mléčného skla".
2016-07-04 10:29:58
fast dispatched and reasonably priced. Good quality , I will order some more of this in the near future
2019-07-02 00:51:13
fast delivery, looks good, but yet to fit
2017-06-06 07:23:40
Good quality
2016-06-24 11:55:16
Very easy to apply and added a very good look to our cabinets
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