substituents

Alana: I’m cold

Zoe: Here take my jacket

Evan: I’m cold too

Jared: WELL DAMN EVAN I CAN’T CONTROL THE WEATHER

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

Cinnamon Apples

Just made delicious cinnamon apples! My mom always used to make these for me either as a side dish or a little desert. Super easy and that perfect Fall treat!

1. Peel and chop 2 apples into small cubes (I like using Granny Smith)

2. Put them in a small pot or pan on medium heat.

3. Add some butter (appx. 1 tbsp)

4. Heat until the apples begin to soften, 5 minutes give or take. They won’t be that soft, but you’ll smell that the sugars start to carmelize.

5. Add a small bit of water (2 tbsp, I really just eyeball it. Like the amount that will fit in a mixing spoon)

6. Add brown sugar (again I eyeball but it’s less than ¼ c. Just a handful, maybe a little less)

7. Sprinkle in as much cinnamon as you deem appropriate

8. Stir until saucey, remove from heat, and serve!

I usually eat mine just like that but it’s good over yogurt, ice cream, sometimes I eat it with a piece of toast. This is my one of my favorite deserts, I’m not a fan of pie crust so it’s my perfect substitue. Plus it’s quick and easy to clean up! Enjoy! 🍎💛

anonymous asked:

Viki could you pls write something fluffy? I'm feeling so down rn I don't know what to do :( My word is sweater, if you want it

i hope you’ll feel better soon.💗
isak is sitting outside their balcony with his phone, and after the last days of the burning heat, there are now white clouds spreading through the whole sky, no sun in sight and there’s a wind thats more than a breeze and it sends shivers down on isaks naked arms but he barely notices bc of the constant incoming messages in the groupchat. he finds himself smiling at jonas ditching magnus to be with eva instead and although the thousand broken heart emojis magnus sends in response makes him pout a little, he takes a deep breath at the fact that jonas and eva are a thing again, feeling a rush of nostalgia come over him. it fades when the balcony door opens and even slips through them with a bright smile, substitue for the sun, and he places two cups on the little table in front of their bench, isak locking his phone and giving a soft smile up at him before it turns into a frown as even disappears back inside with a “ch”. when he’s back outside isak notices a sweater in his hands and sitting down next to him he places it in isaks lap, “you’re cold” and isak fights back with a smile, “i’m not” but he’s pulling the sweater over his head when even raises an eyebrow at the goosebumps on his skin, smiling proudly when isak is done. isak ducks his head and inhales, “smells like you” and even reaches for his own cup, lifting it to his mouth, “we use the same thing in our laundry” and isak rolls his eyes, “i know, i do our laundry, remember?” even pushes his shoulder gently and isak is sure if he wasnt holding his cup, he wouldve pushed harder and he smiles at how even doesnt let one drop of his tea go to waste. “but like. your scent is on it. i can smell you” isak makes sweater paws and blushes. even takes a sip, his cheeks full before he swallows, “yeah? and what do i smell like?” and isaks eyes linger on evens face, the word already on the tip of his tongue but he lets himself stare, because they have all the time  in the world. evens shoulder nudges his, and he licks his lip, “home.” then evens smile fades and he puts his cup down like he hurries, and holds isaks face in both of his hands, eyes searching isaks, the smile back on his face when he finds whatever he was looking for there, and this smile might be one of isaks favourites. evens eyes dont quite crinkle but they open wide and they sparkle, his smile so big isak fears his face is going to split in two. then he blinks and isak notices his eyes start to water, and with a pout he brings his thumb to caress his cheek, ready to catch the teardrop. then even leans in and his lips press softly against isaks own, eyes falling shut, and even tastes sweet, so sweet, isak hums into the kiss and evens fingers hold the sides of his face more secure. then they break and even tilts isaks head so their eyes meet and he chuckles, shaking his head in disbelief. he repeats isaks word then in a whisper, letting the wind carry it around them, finding its way into isaks ears, flowing through his veins, engraving itself onto isaks heart

Non-alcoholic Energon Substitues:

I’ve seen people post pictures of “energon drinks” around a lot but I noticed a pattern… many of them are alcoholic and that can be triggering to someone (or people might just not drink alcohol) and honestly it bothered me a bit how the “default” always seemed to resort to alcohol.

For example, someone would ask one of those kin blogs for beverages that look like energon and the blog will automatically default and resort to alcoholic drinks when… many of the people requesting food/beverage ideas from those blogs are minors or could potentially be triggered by such things.

So here’s a potential list of non-alcoholic (booze-free) drinks that look like energon and taste pretty good.

Jones soda (carbonated):


Calypso (not carbonated – more of a fruit drink):


Slushies (not carbonated):


Icee (vaguely carbonated – thicker than a Slushie):


Crush soda (carbonated):

also comes in a rare blue Crush


Not necessarily a drink but you can put “luster dust” (NOT edible glitter, this stuff is very specific to drinks and doesn’t dissolve) into your drink to give it a quick shimmering look. You can find this edible dust in a baking aisle usually.

Here’s a youtube tutorial on how to make this:

anonymous asked:

15+29. W/Daryl please? ❤

It started off as a night like every other. It ended turning my life upside down. I had recently gotten to Alexandria with everyone else and ever since we got here it had become harder and harder to stay away from Daryl even though I had started to see Spencer. I didn’t know why, I never really liked him anyway. The only one I really ever wanted was Daryl but I had never wanted to risk our friendship just because I couldn’t keep myself together.
It was this night that I finally couldn’t keep it back anymore. I was walking around outside after I had an argument with Spencer. He had accused me of cheating on him with Daryl and even though he wasn’t exactly wrong I had still been far away from it at that point. I couldn’t have guessed that everything was about to change.
“What’cha doin’ out here?”, a familiar voice came from behind me. Daryl was sitting on the front porch, a cigarette between his lips and a bottle of Southern Comfort in his hand.
“Don’t know… Trying to get a clear head, I guess.”
“Can’t help with that”, he muttered reaching the bottle out to me. I sighed and took it from him. Taking a big gulp I sat down next to him not sure what I was trying to do.
“Where’s Spencer?”, he asked taking the bottle back and taking a gulp himself.
“Don’t know.” I reached into his pocket as I used to do ever since, sneaking a cigarette away from him. I placed it between my lips and just seconds later Daryl lit it for me. Just like in the good old days.
“Shouldn’t ya be with him?”, he asked looking me up and down.
“Probably yeah. I guess we’re some kind of couple now…”
“But?”
“It doesn’t feel right. I guess he’s nothing more than a cheap substitute.”
“For what?” Daryl took another big gulp from the bottle. He had obviously no clue that I was talking about him. I envied him for being so fucking oblivious to any kind of romance around him. He would probably never in his life make the first step.He probably didn’t even know how to. I sighed deeply and took the bottle away from him again taking a big gulp.
“A substitue for you, dummy.“
The cigarette almost fell out of Daryl’s mouth as he started coughing in shock.
“For me?”, he gasped looking at me. “What’cha talkin’ ‘bout?”
“Talkin’ ‘bout this”, I muttered flipping my cigarette away before I wrapped my arms around his neck and pulled him down to me. His lips landed hard on mine. He was reluctant at first, just as I had imagined, but as soon as the first shock was gone he deepened the kiss. His hands around my neck he pulled me closer to him, leaving me breatheless. After we separated he just looked at me for a while.
“What?”, I hissed when I couldn’t stand the silence any longer.
“Ya could’ve warned me”, he muttered with a smirk before wrapping his arms around me again.

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. 

2

Healthy Pink Pancakes (glutenfree)

50 g oatflour (can be substitued with normal or whole grain flour)
40 g buckwheat flour (can be substitued with normal or whole grain flour)
10 g vanilla protein powder or 10g more flour*
1 tsp baking powder
cinnamon/vanilla
1 thumb sized piece of raw betroot
½ banana, mashed
1 tbsp liquid sweetener
around ¾ cup water/plantmilk

*if using flour instead of vanilla protein powder, add more sweetener so your pancakes get sweet enough

How to:
Put all ingredients in a high speed blender and blend until you have a smooth and PINK pancake batter. If your batter is too thick to blend, add some more liquid. If you like thick pancakes you shouldn’t use too much liquid. i always add 1 tsp of each chia and flaxseeds to my finished batter, but it’s optional. preheat a pan on medium heat and bake each pancake until it gets dark brownish from both sides. top with whatever you like (i topped mine with chocolate sauce, peanutbutter, fruit and a bliss ball) and enjoy!

tryingtoohardddd  asked:

Quick question on Dantana since you talked about that a bit in your last ask: we all know that Santana didn't love Dani and that they were together for like, a day, but then how come Santana was so fast to go "official" with her? like by the end of 5x02 which was when they met Dani was already her "girlfriend"? i remember being so confused about that when it happened

Hey, @tryingtoohardddd​!

The really short answer here is that Santana essentially rushes into dating Dani because she is trying to convince herself she’s ready to move on from Brittany, even though she is totally, completely not.

The long answer is under the cut, and, gee willikers, is it rambling.

Keep reading

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?

“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.

Keep reading

RFA + Saeran + Vanderwood working at Starbucks

Okay, I’m not sure if anyone would be interested in this, but since I used to work as a barista I started to wonder what our favorite bbies would be like working with MC at Starbucks.

Zen:

Almost never works bar because this gorgeous man bun is too pretty to hide behind an espresso machine. People tip more when he takes their order anyway.

Will always let customers take selfies with him.

Ties his apron extra tight to show of his muscles.

Talks to all the soccer moms once they ask for a manager. Even though he isn’t the manager.

Is only working here until his acting career TAKES OFF!

Yoosung:

Poor bby

Gets flustered so easily, brews too much coffee.

Brings chocolate milk to work every day. He still can’t trust 707.

Couldn’t quite remember drink recipes until you explained them like potions and buffs in LOLOL.

Always forgets to take his breaks.

Usually tries to work the drive through window because he gets to wear a headset.

Jaehee:

This woman, lord help her.

She’s the manager, works at least 60 hours a week.

Stuck writing the schedule every two weeks.

Has to split everyone’s tips.

Clopens (closes -then- opens the next day.)

Knows every recipe, invented at least half of them.

Constantly has to remind 707 -and- Jumin that food safety laws don’t allow pets inside the building/kitchen.

Hasn’t had anything to drink but coffee for years.

Jumin:

HAH

You thought he’d work as a barista?

This boi…

He owns the company. Somehow he bought it from Howard Schultz guys.

Ordered Manager Kang to develop a new latte for Elizabeth the Third.

Demanded revamped lunch sandwiches that include cat-safe foods. Only the best for his precious Elizabeth.

Saeyoung:

I mean, he works here…You think.

The last time he made a latte he broke the espresso machine. Hint: HBC are not a substitue for ground espresso.

Built a robot that cleans the tables…But also spits out creamer at the worst time.

Usually runs drive-through with Yoosung.

HELLO! GOD 707 WELCOMES YOU TO STARBUCKS, WOULD YOU LIKE OUR NEW DRINK?

That new drink has HBC -and- Dr. Pepper.

V:

So calm.

So complacent.

Will remake any drink, no matter the complaint.

Works register with Zen. He’s blind, guys.

Takes all the photos to post on social media to announce new drinks.

Saeran:

This sweet bean…

He stays in the back.

It’s easier to avoid people and their loud noises if he just does dishes.

Glares a bit too hard at complaining customers. Especially if they complain to MC.

Does his best.

Almost gets fired every other day.

Secretly enjoys it when customers yell at Saeyoung. It happens pretty often tbh.

Vanderwood:

What?

This place is disgusting.

When was the last time anyone bleached the drains?

How do you WORK like this?

Seven…STOP that!

This is why we can’t have nice things!

Spends his entire shift cleaning everything, even crawling inside the fridges to scrub and scour the back.