substituents

What stupid news to wake up today… Jon Bokenkamp has decided that there is no place for Agent Gale in Season 5… 

Originally posted by heckyeahreactiongifs

God damn it, but why???  I mean, I really loved this guy. This character was fresh and cheeky and kind of sexy, well sort of … and you all remember the last scene with him and Red in the car???? Sooo good!!! He was fun to watch.

But still they decided to take him out of the game, but hey… we will get lovely dovely Tom back!!! What a substitue!!!! I loved The Blacklist when this little cockroache was away from my screen to play with mommy, cause the series got back it´s flow!! 

Agent Gale was good on the show and I hoped, we would see him from time to time again,but no….

Whenever TPTB find something good, they for sure find a way to make it all go down!! 

If they go back to Keen3 and happy sappy family and Red as “daddy” on top to this fiasco, then this for sure is the last season of The Blacklist, cause it´s simply no longer to endure. At least not for me

So, in memory of Agent Gale… 

Quantitative Structure-Activity Relationship (QSARs) - Drug Development

QSAR modelling predicts the biological activity of a compound based off its physical properties. They are used to avoid synthesising and testing every possible version of a molecule to find the optimum for bioactivity. A small number of structurally similar molecules are synthesised and tested, and these results are used to mathematically predict other similar molecules on a computer.

Hydrophobicity 

This dictates the ease at which a molecule will pass through a cell membrane. Too hydrophobic and the molecule will be drawn to lipids and its bioactivity will be reduced, too hydrophilic and the molecule will be too polar to pass through the phospholipid bilayer and will not carry out its desired activity (will be excreted in urine)

LogP - a measure of the whole molecule’s hydrophobicity 

  • High logP = more hydrophobic
  • Low logP = more hydrophillic (polar)
  • Optimum for bioavailibility = 2-4.5

A regression equation can be formed with c=concentration for max activity

1/c = K1 logP + k2

If linear, values for other similar structures can be taken off the line. If parabolic = logP^2, indicating that after a max concentration bioavalibility will not increase as the drug becomes too hydrophobic and moves into fats.

Substituent hydrophobicity constant,  π

Measures the hydrophobicity of individual substituents in a compound.

π = logPX - logPH

X= partition coefficient for substituted compound 

H= partition coefficient for unsubstituted compound (Hydrogen (so if H was in place of the substituent of interest))

  • Compares how hydrophobic a substituent is compared to hydrogen
  • π = +ve –> X= more hydrophobic than hydrogen
  • π = -ve –> X= less hydrophobic than hydrogen

Note: can be used to calculate logP by adding substituents, rather than having to synthesise and test the molecule (clogP = calculated logP)

Electronics

Pharmacokinetics (administration, distribution, metabolism and excretion) rarely depends on hydrophobicity alone. The polarity of a compound dictates its passage through the patient and its binding at point of activity.

Hammett substituent constant, σ

The starting point  is a chemical equilibrium for which both the substituent constant and the reaction constant are arbitrarily set to 1: the ionization of benzoic acid (R and R’ both H) in water at 25 °C.

Provides K0.

RCO2H <–> RCO2- + H+

uses the dissociation constant

kH = [RCO2-][H+] / [RCO2H]

  • If X is electron withdrawing, it will stabilise RCO2- and shift the equilibrium to the right. kX will increase
  • eg NO2, CN, Cl –> +ve  σ
  • If X is electron donating, it will destabilise the RCO2- anion and shift equilibrium to the left, with a drop in kX.
  • eg alkyls, ethyls, methyls = -ve σ

σ = logkX - logkH

Steric properties 

Taft steric parameter, Es = rate of hydrolysis of XCH2CO2Me under acidic conditions

Es = logkX - logKH

If X is physically small, the rate of hydrolysis (time taken to reach tetrahedral intermediate) will be fast.

Here, the size of R affects the rate of reaction by blocking nucleophilic attack by water.

           H             1.24 +ve value: little steric resistance to hydrolysis
         Me             0.00 the reference substituent in the Taft equation
         t-Bu          -2.78 -ve value: large resistance to hydrolysis

Small X = large Es, large X = small Es

Accuracy of calculation decreases as the bulk and length of the chain increases.

Hansch equations put several of the parameters together to compare overall bioavailibility of different compounds.

Craig plots

  • Plots 2 constants
  • functional groups with similar activity will be in the same quadrant
  • the optimum quadrant, eg +ve σ and -ve π, will contain all the substituents worth investigating

3 Stupid things I’ve done and never fully understood how stupid it was until it was too late;

• Do not start self-harming. No, seriously. Don’t. It might seem like something that would ease that helpless feeling. But in the end it doesn’t make anything better. Once you’ve started the habit it is nearly impossible to completely discard of that line of thought. Once your brain is settled in mode “if I physically harm myself to distract myself from the uncontrollable mental pain I will feel better” the urge is going to become extremely hard to control. Find other ways to handle it before you’ve even started harming yourself, because it is so hard to find a substitute for that feeling once you’ve started. I have tried to find other ways, even when you find something that might work a little. You can go months being able to resist… but then something happens. Something that just makes you so desperatly want to ease the mental pain because it’s unbearable. In the back of your mind is always “this works. do this and you’ll feel better”. Part of you listens to that voice, part of you knows it’s wrong. But in that moment you just won’t give a fuck because you’re fucking desperate. Once your mind is a bit more clear you’ll bitterly regret the relapse.  You’ll look at your old scars beside the fresh cuts and feel completey disgusted with yourself. Feeling weak for not being able to resist once again. Hoping no one will see you fucked up because you’re so ashamed. It’s a life long struggle trying to resist. So please do not put yourself in this position to begin with. It only adds to the shit things in your life you need to overcome.  

• Do not start smoking. People start for different reasons, I think for me personally it was just another way of self-harming. It really isn’t a good habit whatsoever, it’s just harmful which I’m sure you already know. But just like cutting, it is a habit that’s incredible hard to get rid of. You will possibly never find a way to get rid of the urge if you don’t find a substitute that really works for you. It’s already inprinted in your brain, you want to take a cigarette waiting for friends, waiting for the subway, having a moment alone outside relaxing, you’re feeling nervous and want a smoke, you want a break just relaxing having a cigarette. It’s incredibly hard to get rid of that line of thinking and finding a substitue if e cigaretts doesn’t work for you, please consider that. It usually starts small, a cigarette here and there with a friend, you gradually do it more and suddenly you’re sitting there like “when the fuck did I get addicted to this”.

 Think about your own well being before others. This is not an addiction like the others, but still hard to change, and to some of you it might sound incredibly selfish. I’d say yes, it is selfish and it is good to be selfish sometimes. That’s something I had to learn the hard way. All my life I’ve been putting other people’s well being before my own and it has honestly been killing me. I think what really made the cup overflow and me realising “I can’t keep doing this” was when the guy I’d been dating committed suicide a little over a month ago. In the ways I was blaming myself, feeling like I failed saving him. You need to realise that it’s not your responsibility to keep someone else alive. Someone else’s well being is not your responsibility. Especially not if it’s dragging yourself down with it. I’m not saying “don’t take care of your friends” of course you should be there for them. I’m just saying, make sure to take care of yourself before you take care of others. And if it has an extremely negative effect on you, it is okay to step back and think about yourself. You shouldn’t feel like you’re trying to keep someone else alive while you’re trying to keep yourself alive at the same time, you know? I’m incredibly ill fitted to take care of people that way when I have so many problems of my own. Deal with your own problems before you deal with others. The other way around just isn’t healthy. It is great to be kindhearted but please be as kind to yourself as you are to your friends. Do not forget yourself. I’m sure there are splitted opinions about this. But that’s what I have learned from own experience.


I might regret sharing this later and I might delete it, But I just wanted to give my point of view in case it maybe could make someone rethink something they’re doing or thought about. 

Queliot au’s

Okay so my au ideas are usually super long but im gonna try and make them shorter so i can make a list of a few:


  • Coffee shop au where Eliot is a sassy little shit who contantly messes with Quentins name, until one day he sees this sad little look on his face and from then on Quentin is the only person who’s name Eliot ever gets right because he really doesn’t like the kicked puppy dog look on Quentins face, even though he will never, ever admit it. (Until they finally get together and Quentin asks why he started doing his name right and there’s there puppy dog eyes and Eliot can’t lie when Quentin is looking at him like that)
  • AU where Quentin realizes something is really, really wrong with Eliot after the whole Mike debacle and slips a truth serum in one of Eliot’s drinks so he has no choice but to talk to Quentin, and Eliot’s reaosnably pissed but after he gets all of the pain off his chest, and he and Quentin just lie in bed staring at the ceiling, he finds that he feels a bit better and Quentin fucking sucks because somehow he knows exactly what to do or say to make Eliot feel better, dammit.
  • AU Where Margo is waiting for Quentin when he stumbles into Brakebills and she sees him as this cute little nerd that she decides to take under her wing and then introducdes him to Eliot, and then Eliot still falls in love with him, but Margot is kind of the driving force that steers him away from Alice and into Eliots arms.
  • AU where when Quentin wakes up from the web, Eliot pats him on the head, but then he slides down the couch and pulls Quentin into the tightest, homiest hug he possibly can because he almost lost him and that’s not okay, and after that they become inseparable
  • Au where Quentin finds out that Eliot gets to have a husband and a wife and brings it up to him all nonchalant like, “So you can marry some dude you find hot,” And he’s totally wishing its him, but he doesn’t think Eliot’s interested, until Eliot smirks at him, and says, “Great. So when do you want to do this?”
  • CHEF AU i dont even care. Eliot is the head chef, and Quentin is either a waiter or a chef in training or something, but Eliot woos Quentin with nothing other than saucy meals that substitues ats aphrodisacs, and it takes Quentin forever to realize that these are all date meals that Eliot cooks for him because Quentin is so blissfully and painfully unaware of any advances Eliots makes towards him
  • Harry Potter au where Quentin literally risks his life and runs onto the quidditch pitch when Eliot is knocked off his broom. 

I have so many more but my lunch break is almost over so here have this for now?

Thunder Breastar and Geed

Here we can sorta compare the Zoffy x belial and Ultraman x belial fusion.

Although zoffy and Ultraman looks virtually the same, the fusion sorta sets them apart with Thunder Breastar being more buff in contrast to Primitive’s relatively lean physique.

Also noteworthy is that Primitive has blades on his arm similar to Thunder Stream while thunder Breastar dosent have.

In addition, primitive lacks the claws that the rest of the fusions which includes belial as a substituent have.

Does the above 2 considerations have something to do with both fusions having a different ‘host form’(Orb and Geed)? Or a design screwup? We’ll have to see geed’s original form(assuming he has one) to draw anymore logical conclusions.

https://mobile.twitter.com/tytoalbamazon

De l'usage du point-virgule et de la virgule.
  • M. Benoît Hamon, ministre délégué : C’est un amendement de précision rédactionnelle qui vise à substituer un point-virgule à une virgule et à supprimer une seconde virgule.
  • [...]
  • M. Christian Eckert, rapporteur : La commission mixte paritaire a longuement discuté de cette virgule.
  • M. Paul Giacobbi : Plus exactement de son point !
  • M. Christian Eckert, rapporteur : Comme quoi, parfois, chaque détail a son importance.
  • [...]
  • M. Hervé Mariton : Monsieur le ministre, je ne veux pas faire preuve de pointillisme rédactionnel mais, normalement, après un point-virgule, il y a un verbe. Je veux bien que le Gouvernement essaie de s’en sortir en nous expliquant ce qu’il veut faire dans un texte auquel pas grand monde ne comprend grand-chose – d’où la difficulté hier en CMP –, mais pouvez-vous m’indiquer où est le verbe ? Vos explications étaient à peu près claires mais le texte, même avec un point-virgule, ne l’est pas.
  • [...]
  • M. Charles de Courson : Nous sommes face à un problème sérieux. [...] Que signifie cette étrange modification de la ponctuation ?
  • [...]
  • M. Christian Eckert : nous avons eu, ici, certains s’en souviennent, une séance épique au cours de laquelle nous avons discuté du taux d’imposition de la salade à emporter suivant qu’il y avait ou non des couverts en plastique. (Sourires.) Les jus de fruit, selon qu’ils étaient vendus avec une paille ou non, bénéficiaient aussi d’un traitement différent.
  • [..]
  • M. Benoît Hamon, ministre délégué : Monsieur Mariton, j’espère que la réponse du rapporteur sur le point-virgule vous a satisfait.

Known by one name yet possessing the faces of many, the Zoroark takes pleasure in taunting of those who are suffering. His power contained in his hulking bulk spoke that of an ancient ominous being, the faded red markings on his forehead faintly recognizable, familiar. 

Yet that time had passed and he found himself trapped in an ominous forest. With an army of substitues at his disposal, he shows empathy to some and cruel to others. 

The fox is ever unpredictable, you should always be on your guard. But you will never discover it was truly him, wearing one of his deceitful masks.

@askillusionfox (I could have sworn I was following this but apparently not?? Wth)

“Please Don’t Lie To Me”

Summary: If there was one thing Marinette hated more than her thread snapping in her sewing machine it was liars.  So when it seems Adrien has lied to her, Marinette must deal with her idealistic future being just a dream and figure out how to interact with him now.

Hello @celestialanatomy I’m your substitue @mlsecretsanta .  I hope you enjoy the first installment of your gift.  I also want to thank @breeeliss & @miraculousstorytelling for helping me with planning this.

(AO3)

~~~~

‘I can do this, I can do this,’ was Marinette’s mantra all day.  It was something she wanted to do for a while now.  She was going to ask Adrien to come over to her house.  So far the only times he’d come over had been due to school activities (and the time her Uncle came to visit).  Today however she was going to ask him to come over not for homework, but to play video games.

Marinette didn’t do it in the morning, that was usually when Chloé attacked him and Nino and him had their bro time.  She wouldn’t interrupt ritual bro time, and as for Chloé, she was trying not to antagonize the blonde when it wasn’t necessary.  Instead Marinette waited until they were all getting up for their lunch break.

“H-hey Adrien,” Marinette went down the step, standing beside Adrien’s desk.  He looked up at her and smiled and not for the first time Marinette felt her heart skip a beat.  How did he have no idea how he affected her so?

“Oh, hey there Marinette,” was his reply.  Did his eyes sparkle or was that in her mind?

“I w-was wondering,” she started and noticed his head tilt in that adorable fashion.  Her mind supplied the image of a curious cat, but she quickly squashed that thought. “Did you want to come over to play Mecha Strike or some other games?”

She did it!  Marinette asked Adrien to come over!  She was so proud of herself right now.  She was pretty sure Tikki was proud of her too. When Alya heard she’d also be proud.  This was a proud moment in Marinette’s life.

“I’d like to,” Adrien said, and Marinette felt her heartbeat race. “But I can’t.” And suddenly it’s plummeted.  “I have extra piano lessons after class today.”

“Oh, well, maybe some other time?” Marinette would keep that smile plastered on her face.

Adrien nodded in what Marinette thought was an enthusiastic fashion. “Sure thing.”

And that was how Marinette did not get Adrien to come over to her house.  She was a little disappointed, but overall it was a good conversation.  Adrien had a prior commitment and Marinette understood that his schedule was busy.  She was encouraged to try again in the near future.

It was those thoughts that sustained Ladybug in battle, her day neatly being pulled off track by an akuma.  Chat Noir and she were able to corner the newest of Hawk Moth’s victims after about a half hour of battle.  When finally Snack Attack was defeated using a plastic coat hanger, it was only an hour since school had gotten out.

One fist bump later, and double checking the victim was going to be already getting themselves back home, Ladybug was looking for a nice hidden place to detransform.  She was in the wrong arrondissement and would have to let Tikki charge up to get herself back home.  Either that or take the Metro, but Ladybug could get there a lot sooner.

She was feeding Tikki in an alleyway, about to walk onto the sidewalk when she noticed a familiar figure walking by.  Was that Adrien?

There was no reason for Adrien to be in this part of Paris, not if he had piano practice.  Yet there he was smiling to himself, walking casually by, occasionally looking into shop windows. She caught him plucking at the front of his over shirt more than once as well.

Adrien Agreste was wandering around as though he hadn’t a care in the world and Marinette didn’t understand why.  Why would he tell her he couldn’t come over?  Unless? And Marinette’s heart sank as the idea wormed it’s way into her mind.  Adrien had lied to her.

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Healthy vegan Waffles

for 1 hungry person (like pictured)
50 g oat flour*
25 g wholegrain spelt flour
15 g wholegrain buckwheat flour*
10 g vanilla protein powder (optional)
1 teaspoon baking powder
cinnamon/vanilla
½ mashed banana
1 big tsp date syrup/agave nectar/maple syrup
water/plantmilk

*both flours can be substitued with wholegrain spelt flour. or just normal all purpose flour.

How to:
mix all dry ingredients together. add mashed banana and syrup and add as much plantbased milk/water as you need until you have a thick batter. you honestly don’t need to measure the liquid- the batter shouldn’t be runny- it should just be like a normal thick waffle batter. if the batter is too thin, the waffles get really thin and crispy (we don’t want that!). once you’ve mixed everything together, you can add half a tablespoon of each chia and flaxseeds. it helps the waffles to stick together in the waffle iron. Preheat your waffle iron (i have a really good one and don’t need any oil at all) and bake each waffle until ready. top with your favorite toppings and enjoy!


PLEASE DO NOT REBLOG :)