Lesson 4 - SMILES (Introduction to SMILES, and how to make SMILES notaiions using ChemSketch)

Bismillahirrahmanirrahim and good morning.

     Alhamdulillah, praise to Allah, we still have a chance to live in His blessing. Well, today we has learned new thing which is SMILES.At first, we had thought that Smiles is this:

However, this SMILES that we learned is different, it is about SMILES notations.  What is SMILES? SMILES is an acronym for Simplified molecular-input line-entry system. It is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules (source : HERE). 

     This SMILES notation is widely used and also very efficient computationally.It uses atomic symbol and a set of intuitive symbols. Furthermore, it uses hydrogen-suppressed molecular graphs (HSMG), which basically men=ans that for example, in writing molecular formula (for example, propane), instead of writing the chemical structure as follows :

We just write it as CCC. This is what we called HSMG in SMILES notations, as we neglect the hydrogen atoms.

     In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph. The chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses "the brackets ()" are used to indicate points of branching on the molecular structure. For example, 2-methylpentane an be written as CC(C)CCC. For molecular bondings, we use symbols as follows :

• for single bond we use - symbol (can be omitted)
• for double bond we use = symbol
• for triple bond we use # symbol
• For arimatic we use : symbol (also can be omitted)

     

     For branches, as stated before, we can use parenthesis to indicate them. The parenthesis symbol can be either nested or stacked. Example of branched molecules :

• CC(O)CC is 2-Butanol
• OCC(C)C is iso-Butanol
• OC(C)(C)C is tert-Butanol

     Then, for aliphatic carbon, we use big capital C and for aromatic one, we use small capital c. For atomic charges, we can specify the atoms and the charges in a square brackets. For examples : 

• [H⁺] proton
• [OH^-] hydroxyl anion
• [OH₃⁺] hydronium cation
• [Fe²⁺] iron(II) cation
• [NH₄⁺] ammonium cation

     For SMILES Cyclic Structures, we can degign notaions by breaking one single or one aromatic bond in each ring and number it in any order

–Designate ring-breaking atoms by the same digit following the atomic symbol

Numbers indicate start and stop of ring :

• Same number indicates start and end of the ring, entered immediately following the start/end atoms
• Only numbers 1 –9 are used
• A number should appear only twice
• Atom can be associated w. 2 consecutive numbers, e.g., Napthalene: c12ccccc1cccc2

There are few restrictions in doing SMILES notations :

     Avoid two consecutive left parentheses if possible

     Strive for the fewest number of possible branches

     Tautomeric bonds are not designated; enter the appropriate form

     A branch cannot begin a SMILES notation

     A branch cannot immediately follow a double-or triple-bond symbol

     Example: C=(CC)C is invalid, but

     C(=CC)C or C(CC)=C are valid SMILES

For isomeric and chiral SMILES :

     Isomeric configuration indicated by forward and backward slashes: / \

     Examples:

          –trans-1,2-dibromoethene: Br/C=C/Br

          –cis-1,2-dibromoethene: Br/C=C\Br

     Chirality indicated by the “@” symbol

     Then, we will demonstrate how to use SMILES notations by using ChemSketch..

• GENERATING SMILES NOTATION FOR BENZYLAMIDE

By using ChemSketch, firstly, we click structure and we choose benzene diagram. We continued by clicking the carbon symbol and linked the bond of carbon to the benzene ring. Lastly, we click the nitrogen symbol and connected to the structure. To notate the structure, we click draw then go to the tools and choose generate and then click SMILES notation. At the end, the notation of the structure given as follows :

• GENERATING SMILES NOTATION FOR FLUORENE 

Generate Fluorene compound using the template provided in the Chemsketch

Using Draw mode, highlight the compound.

 Then, select ‘Tools’ in the Menu Bar.

Choose, ‘Generate’ in the ‘Tool’.

  Lastly, select SMILES notation.

 Finally, the SMILES notation is generated.

In addition, repeat (2) until (4) and select ‘Name for Structure’ to generate the structure’s name.

• GENERATING SMILES NOTATION FOR PARACETAMOL

Draw the N-(4-hydroxyphenyl)acetamide or paracetamol using a chemsketch. Open structure mode and click C for carbon, O for OH and N for NH which are situated on the left side. Click the benzene ring structure on the right side to create a benzene ring.Open tools on chemsketch and select generate then select name for structure to insert the name. Select generate again and this time select SMILES notation to put the notation.