when running parameter estimation, it is quite common, to get into regions, where simulation becomes numerical difficult. During the time course simulation the integrator would have needed more steps, then the default '100000' specified in the Time-Course Task. If you change the value of 'Max Internal steps', this might help. Though you might also want to double check the bounds on the parameters to estimate, to see whether you could narrow them more to avoid those regions.
As for the Fisher information matrix, this is a metric, that basically tells you how much the provided data tells you about the parameters you are estimating. If it is singular, that means there are rows in there with zeros, which gives you an indication that there is little information for this parameter in the data you provided.