Assemble 2.0 Tutorial

Brief Description | First Example | Fundamental difference between non-overlapping fragments and substructure constraints | Atom Tags | Assemble as a tool in structure elucidation | Ranking | Postprocessing

Atom Tags

As it is so important to choose fragments as large as possible, some more functionality is built into Assemble's ability to treat overlap. The atoms of fragments can be augmented with structural information about their immediate environment. The scope of these atom tags reaches beyond the fragment. An atom can have as many atom tags as desired. It is important to note that atom tags can only be added to non-overlapping fragments, not to substructure constraints. If you tick the "overlap" box, tag information is ignored.

Neighboring Atom Tag

Possibly the most important atom tag is the neighboring atom tag. It specifies how many atoms of a particular element are bonded to the atom. These atoms need not be part of the fragment, but can. Optionally the hybridization of the atoms can be specified, as can the bond type. The number of atoms can be specified as a range.

Example 1
The presence of an ethoxy group can easily be derived from the H-1 nmr spectrum by the integrals and the coupling patterns of the signals involved. The chemical shift above 4 ppm for the CH2 group imposes an oxygen atom to be bonded to the CH2 group. Individual oxygen atoms cannot be easily identified by any property. Therefore if an ether-like oxygen atom appears in other non-overlapping fragments, no more ether-type oxygen atoms must appear in fragments. Their presence is therefore indicated by a neighboring atom tag.

To add a tag to an atom first draw the fragment without tags as you learned before. Draw an ethyl group. After finishing, change the main mode of the editor from drawing to selecting/moving by clicking the middle field in the "Main Modes" block, as shown below.

In this mode you can click on any atom, thereby selecting it. Its color changes to red. You can select as many atoms as you want. You can deselect the atoms by clicking on an empty spot in the drawing area. If no atom is selected, clicking an empty spot will select all atoms. As you want to add an atom tag to the CH2 group, select it by clicking on it.

Atom tags are set up in a separate window. To pop it up move the mouse pointer anywhere into the drawing area and press the right mouse button. A menu appears. Select the row "Show Atom Tag Dialog":

When you release the mouse button, the atom tag dialog window pops up:

Seven kinds of atom tags can be managed. Select the neighboring atom tag by clicking its (top) row. Choose oxygen as the element symbol of the neighboring atom. If required, you can specify how many hydrogen atoms the neighboring atom has to be bonded to. As you don't want to specify this property, leave the field blank, or clear it if you find an entry. Choose hybridization and bond type to "any" by clicking the first button. Finally choose the minimum and maximum occurrence both to 1. You have now set up the tag as desired. Apply it to the previously selected CH2 group by clicking the "Add" field. You find the tag as a red on yellow text field next to the tagged atom.

This fragment can now be moved to the assemble main window as you did before.

Example 2
The number of hydrogen atoms specified to be bonded to other atoms are lower limits. In the assembly process a CH2 group can be expanded to a CH3 group. If this is to be prevented, the upper limit for the number of hydrogen atoms can be specified by a neighboring atom tag.

Although the tagged CH2 group has a free valence, it will not change to a CH3 group.

Example 3
An atom cannot be part of a fragment if its element type is not exactly known. Consider the situation that the C-13 chemical shift and the frequency in the IR spectrum can be accounted for by an amide or an ester linkage. The atoms of the carbonyl group can be part of a fragment, but the hetero atom bonded to it cannot, though no other oxygen or nitrogen atom may appear in the other fragments. As the element is not exactly known, the hetero atom can only be included in a neighboring atom tag. As there is already an oxygen atom bonded to the carbonyl carbon atom, the hybridization sp3 for the hetero atom has to be specified to avoid interference.

The free valence of the tagged atom has to become an sp3 hybridized oxygen or nitrogen atom. The carbonyl oxygen atom is sp2 hybridized, so the tag does not apply to it.

Cycle Size Atom Tag

Atoms in small rings often show a behavior clearly distinct from unstrained environments. If a particular atom is believed to be member of a ring, this information can be passed to Assemble by means of the cycle size atom tag. The cycle size can be given as a range. The minimum and maximum number of cycles, the atom has to be member of, can also be specified. The feature can be used to prevent the atom from being member of a ring by specifying the corresponding maximum occurrence as 0.

Example
There is a very strong band in the IR spectrum at 1780 cm-1 corresponding to a carbonyl group. In the C-13 nmr spectrum is a signal at 177.8 ppm corresponding to a carbonyl environment. The chemical shift is too low for a ketone, so a hetero atom must be bonded to the carbonyl group. Unusually high IR frequencies are experienced when the carbonyl carbon atom is a member of a small ring, in this case most likely a 5-membered ring, maybe 4-membered . Therefore the compound is a 4-5-membered lactone or lactame. The latter is excluded by the molecular formula C5 H8 O2. This information is given by setting up the following cycle size atom tag:

The tag information is applied to the carbonyl carbon atom of an ester linkage:

Branch Composition Atom Tag

Occasionally the elemental composition of a fragment is known without any further knowledge about the connectivity within the fragment. The mass spectrum may show the loss of m/e = 71 from the molecule ion. It is believed that this corresponds to a direct fragmentation next to a carbonyl group. The carbonyl group itself accounts for m/e = 28, the remainder of 43 is assumed to be C3H7, so it is a propyl or isopropyl group. As C3H7 is a terminal fragment, irrespective of its connectivity, the information can be passed to Assemble by the branch composition atom tag.

The tag is assigned to the carbon atom of a carbonyl group.

One of the free valences of the carbonyl group has to be a terminal group with elemental composition C3H7.

Vicinal Hydrogen Atom Tag

The coupling patterns in the H-1 nmr spectrum yields information about the intermediate environment of an atom. In first order spectra it is often possible to determine the number of vicinal hydrogens, i.e., hydrogens 3 bonds apart from the resonating hydrogen atom(s). It is not possible though to determine the exact connectivity. Assemble allows you to specify the number of vicinal hydrogen atoms that are coupling with a particular hydrogen bearing atom. As hydrogen is treated as a special case in Assemble, the information is given to the atom that is bonded to the resonating hydrogen. Request exactly 5 vicinal hydrogen atoms by a vicinal hydrogen atom tag:

The central CH group in the following two fragments has 5 vicinal hydrogens. Although the connectivity is different, they both satisfy the atom tag. In first order spectra, assuming similar coupling constants, the signal of the central CH group would appear as a 6-line system in both cases, without the possibility to distinguish between the two cases. Note that the content of the window is not suited to be passed to Assemble, as it contains two separated fragments. It is just shown for illustration.

a,b-Unsaturation Atom Tag

Sometimes an atom is known to be part of an unsaturated system. A keto-carbonyl group may leave its traces in the C-13 nmr spectrum at a chemical shift below 200 ppm, which suggests the ketone is a,b-unsaturated. Assemble allows you to impose this environment. The atoms required to form the unsaturated system may be part of the fragment, but need not.

The tag is applied to the carbon atom of a carbonyl group.

Hybridization Atom Tag

The hybridization atom tag can be used to specify the hybridization of an atom. It is important to remember that Assemble handles constitutions. The hybridization in this context is information about the bond types that emerge from the atom, not their spacial arrangement. A nitrogen atom with three single bonds may be planar or not, it is considered sp3 hybridized.

Example
The hybridization of a carbon atom has a great influence on its nmr chemical shift. Modern 2d nmr experiments yield connectivity information without imposing any kind of bond type. The hybridization, which is also readily available from the chemical shift information, partially makes up for this deficiency. To declare atoms sp2 hybridized, set up a hybridization tag.

The following fragment is a typical example as derived from 2d nmr experiments. The bond types are not known, the hybridizations are.

Although two sp2 hybridized CH groups are directly bonded, it is not clear whether the bond between them is single or double, so it is left unspecified.

Internal Unsaturation Atom Tag

Any two atoms within a fragment are allowed to form a bond between them in the assembly process, except for direct neighbors. Sometimes it is known that, within a particular fragment, no additional bonds must be formed. This information can be passed to Assemble by employing the internal unsaturation tag. The tag does not have any arguments and can be placed on any atom of the fragment. The tag precludes the formation of any new multiple bond linkages within the entire tagged fragment. Cycle formation that is the result of internal bridging, i.e., involving no atoms external to the tagged fragment, is also forbidden.

Example
When a benzene ring is known to be in the molecule, it is possibly not sufficient to specify it as a fragment. In the assembly process two free valences of the ring could form an additional bond across the ring. The resulting ring system has a behavior clearly different from a benzene ring. Internal bonding is therefore forbidden by tagging any atom of the fragment. The internal unsaturation atom tag does not have any parameters:

It can be applied to any atom of the fragment, or to several atoms.